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West, Jennifer L

Overview:

Jennifer West’s research in biomaterials and tissue engineering involves the synthesis, development, and application of novel, biofunctional materials, and the use of biomaterials and engineering approaches to study biological problems. Current projects include the design of ECM-mimetic hydrogel materials, novel microfabrication strategies for biomimetic patterning, and nanoparticle theranostics.

Positions:

Fitzpatrick Family University Professor of Engineering

Biomedical Engineering
Pratt School of Engineering

Professor in the Department of Biomedical Engineering

Biomedical Engineering
Pratt School of Engineering

Associate Dean for Ph.D. Education

Pratt School of Engineering
Pratt School of Engineering

Professor in the Department of Mechanical Engineering and Materials Science

Mechanical Engineering and Materials Science
Pratt School of Engineering

Professor of Cell Biology

Cell Biology
School of Medicine

Professor of Chemistry

Chemistry
Trinity College of Arts & Sciences

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Affiliate of the Regeneration Next Initiative

Regeneration Next Initiative
School of Medicine

Education:

Ph.D. 1996

Ph.D. — University of Texas at Austin

News:

Grants:

Medical Scientist Training Program

Administered By
School of Medicine
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 1997
End Date
June 30, 2022

Development of a New Generation Micro-CT imaging for Functional and Molecular Imaging of Cancer

Administered By
Radiology
AwardedBy
National Institutes of Health
Role
Co Investigator
Start Date
July 01, 2015
End Date
June 30, 2020

Training in Medical Imaging

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 15, 2003
End Date
August 31, 2019

An Activatable Nanoparticle Probe for Molecular Imaging of Protease Activity by Dual Energy CT

Administered By
School of Medicine
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
June 01, 2015
End Date
May 31, 2018

University Training Program in Biomolecular and Tissue Engineering

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Mentor
Start Date
July 01, 1994
End Date
June 30, 2017

Modulating Cell Phenotype during Tubulogenesis through 3D Micropatterning

Administered By
Biomedical Engineering
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
September 01, 2013
End Date
August 31, 2016

An Injectable Method for Posterior Lateral Spine Fusion

Administered By
Biomedical Engineering
AwardedBy
United States Army Medical Research Acquisition Activity
Role
Principal Investigator
Start Date
September 01, 2012
End Date
August 31, 2016

Texas Center for Cancer Nanotechnology Excellence

Administered By
Biomedical Engineering
AwardedBy
University of Texas Health Science Center at Houston
Role
Principal Investigator
Start Date
August 01, 2012
End Date
July 31, 2016

Neurovascular Regeneration

Administered By
Biomedical Engineering
AwardedBy
Yale University
Role
Principal Investigator
Start Date
January 15, 2014
End Date
December 31, 2015

Dual energy CT molecular imaging of vulnerable atherosclerotic plaques using a novel nanoparticle contrast agent

Administered By
Biomedical Engineering
AwardedBy
American Heart Association
Role
Principal Investigator
Start Date
July 01, 2014
End Date
May 31, 2015
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Awards:

National Academy of Inventors. National Academy of Inventors.

Type
National
Awarded By
National Academy of Inventors
Date
January 01, 2017

President's Circle Lecturer. National Academies of Science, Engineering and Medicine.

Type
National
Awarded By
National Academies of Science, Engineering and Medicine
Date
January 01, 2017

Capers and Marion McDonald Teaching and Research Award. Pratt School of Engineering.

Type
School
Awarded By
Pratt School of Engineering
Date
January 01, 2016

National Academy of Engineering. National Academy of Engineering.

Type
National
Awarded By
National Academy of Engineering
Date
January 01, 2016

Clemson Award. Society for Biomaterials.

Type
National
Awarded By
Society for Biomaterials
Date
April 22, 2015

ACS Editors' Choice Manuscript. ACS Journals.

Type
National
Awarded By
ACS Journals
Date
January 01, 2015

Thomson Reuters Highly Cited Researcher in Materials Science. Thomson Reuters.

Type
National
Awarded By
Thomson Reuters
Date
January 01, 2014

Admiral of the Texas Navy. Governor of Texas.

Type
National
Awarded By
Governor of Texas
Date
February 01, 2012

Best Discovery of 2003. Nanotechnology Now.

Type
National
Awarded By
Nanotechnology Now
Date
February 01, 2012

BioHouston's 2009 Women in Science Award. Unknown.

Type
Other
Awarded By
Unknown
Date
February 01, 2012

CAREER Award. National Science Foundation.

Type
National
Awarded By
National Science Foundation
Date
February 01, 2012

Duncan Award for Outstanding Academic Achievement. Rice University.

Type
National
Awarded By
Rice University
Date
February 01, 2012

Excellence in Research Mentorship Award. Rice University.

Type
National
Awarded By
Rice University
Date
February 01, 2012

Fellow. American Institute for Medical and Biological Engineering.

Type
National
Awarded By
American Institute for Medical and Biological Engineering
Date
February 01, 2012

Fellow. Biomedical Engineering Society.

Type
National
Awarded By
Biomedical Engineering Society
Date
February 01, 2012

Frank Annunzio Award. Christopher Columbus Foundation.

Type
International
Awarded By
Christopher Columbus Foundation
Date
February 01, 2012

HSEMB Oustanding Young Scientist Award. Unknown.

Type
Other
Awarded By
Unknown
Date
February 01, 2012

Hershel M. Rich Invention Award. Rice University.

Type
National
Awarded By
Rice University
Date
February 01, 2012

Howard Hughes Medical Institute Professor. Unknown.

Type
Other
Awarded By
Unknown
Date
February 01, 2012

Inventor of the Year Award. State Bar of Texas.

Type
National
Awarded By
State Bar of Texas
Date
February 01, 2012

J. M. Chance Prize for Excellence in Teaching. Rice University.

Type
National
Awarded By
Rice University
Date
February 01, 2012

Most Cited Paper. Annual of Biomedical Engineering.

Type
National
Awarded By
Annual of Biomedical Engineering
Date
February 01, 2012

Most Highly Cited Papers. NanoLetters.

Type
National
Awarded By
NanoLetters
Date
February 01, 2012

Nanotechnology Researchers of the Year. Small Times Magazine.

Type
National
Awarded By
Small Times Magazine
Date
February 01, 2012

O'Donnell Award in Engineering. The Academy of Medicine, Engineering and Science of Texas.

Type
National
Awarded By
The Academy of Medicine, Engineering and Science of Texas
Date
February 01, 2012

Outstanding Faculty Associate. Weiss College, Rice University.

Type
National
Awarded By
Weiss College, Rice University
Date
February 01, 2012

Outstanding Research in Drug Delivery Award. Cygnus-CRS.

Type
National
Awarded By
Cygnus-CRS
Date
February 01, 2012

Outstanding Younger Investigator Award. Society for Biomaterials.

Type
National
Awarded By
Society for Biomaterials
Date
February 01, 2012

Parke-Davis Atorvastatin Research Award. Unknown.

Type
Other
Awarded By
Unknown
Date
February 01, 2012

Quantum Award. National Institute of Health, NIBIB.

Type
National
Awarded By
National Institute of Health, NIBIB
Date
February 01, 2012

Samuel Lunden Scholarship. Massachusetts Institute of Technology.

Type
National
Awarded By
Massachusetts Institute of Technology
Date
February 01, 2012

Secretariat Lecturer. American Chemical Society.

Type
National
Awarded By
American Chemical Society
Date
February 01, 2012

Tech Review TR 100 Most Innovative Young Scientists. MIT Technology Review.

Type
National
Awarded By
MIT Technology Review
Date
February 01, 2012

University Fellow. University of Texas.

Type
National
Awarded By
University of Texas
Date
February 01, 2012

Fellows. American Institute for Medical and Biological Engineering.

Type
National
Awarded By
American Institute for Medical and Biological Engineering
Date
January 01, 2005

Young Investigator Award. Society for Biomaterials.

Type
National
Awarded By
Society for Biomaterials
Date
January 01, 2000

Publications:

Ascorbic acid promotes extracellular matrix deposition while preserving valve interstitial cell quiescence within 3D hydrogel scaffolds.

Current options for aortic valve replacements are non-viable and thus lack the ability to grow and remodel, which can be problematic for paediatric applications. Toward the development of living valve substitutes that can grow and remodel, porcine aortic valve interstitial cells (VICs) were isolated and encapsulated within proteolytically degradable and cell-adhesive poly(ethylene glycol) (PEG) hydrogels, in an effort to study their phenotypes and functions. The results showed that encapsulated VICs maintained high viability and proliferated within the hydrogels. The VICs actively remodelled the hydrogels via secretion of matrix metalloproteinase-2 (MMP-2) and deposition of new extracellular matrix (ECM) components, including collagens I and III. The soft hydrogels with compressive moduli of ~4.3 kPa quickly reverted VICs from an activated myofibroblastic phenotype to a quiescent, unactivated phenotype, evidenced by the loss of α-smooth muscle actin expression upon encapsulation. In an effort to promote VIC-mediated ECM production, ascorbic acid (AA) was supplemented in the medium to investigate its effects on VIC function and phenotype. AA treatment enhanced VIC spreading and proliferation, and inhibited apoptosis. AA treatment also promoted VIC-mediated ECM remodelling by increasing MMP-2 activity and depositing collagens I and III. AA treatment did not significantly influence the expression of α-smooth muscle actin (myofibroblast activation marker) and alkaline phosphatase (osteogenic differentiation marker). No calcification or nodule formation was observed within the cell-laden hydrogels, with or without AA treatment. These results suggest the potential of this system and the beneficial effect of AA in heart valve tissue engineering. Copyright © 2015 John Wiley & Sons, Ltd.

Authors
Wu, Y; Puperi, DS; Grande-Allen, KJ; West, JL
MLA Citation
Wu, Y, Puperi, DS, Grande-Allen, KJ, and West, JL. "Ascorbic acid promotes extracellular matrix deposition while preserving valve interstitial cell quiescence within 3D hydrogel scaffolds." Journal of tissue engineering and regenerative medicine 11.7 (July 2017): 1963-1973.
PMID
26631842
Source
epmc
Published In
Journal of Tissue Engineering and Regenerative Medicine
Volume
11
Issue
7
Publish Date
2017
Start Page
1963
End Page
1973
DOI
10.1002/term.2093

Stiffness of Protease Sensitive and Cell Adhesive PEG Hydrogels Promotes Neovascularization In Vivo.

Materials that support the assembly of new vasculature are critical for regenerative medicine. Controlling the scaffold's mechanical properties may help to optimize neovascularization within implanted biomaterials. However, reducing the stiffness of synthetic hydrogels usually requires decreasing polymer densities or increasing chain lengths, both of which accelerate degradation. We synthesized enzymatically-degradable poly(ethylene glycol) hydrogels with compressive moduli from 2 to 18 kPa at constant polymer density, chain length, and proteolytic degradability by inserting an allyloxycarbonyl functionality into the polymer backbone. This group competes with acrylates during photopolymerization to alter the crosslink network structure and reduce the hydrogel's stiffness. Hydrogels that incorporated (soft) or lacked (stiff) this group were implanted subcutaneously in rats to investigate the role of stiffness on host tissue interactions. Changes in tissue integration were quantified after 4 weeks via the hydrogel area replaced by native tissue (tissue area fraction), yielding 0.136 for softer vs. 0.062 for stiffer hydrogels. Including soluble FGF-2 and PDGF-BB improved these responses to 0.164 and 0.089, respectively. Softer gels exhibited greater vascularization with 8.6 microvessels mm-2 compared to stiffer gels at 2.4 microvessels mm-2. Growth factors improved this to 11.2 and 4.9 microvessels mm-2, respectively. Softer hydrogels tended to display more sustained responses, promoting neovascularization and tissue integration in synthetic scaffolds.

Authors
Schweller, RM; Wu, ZJ; Klitzman, B; West, JL
MLA Citation
Schweller, RM, Wu, ZJ, Klitzman, B, and West, JL. "Stiffness of Protease Sensitive and Cell Adhesive PEG Hydrogels Promotes Neovascularization In Vivo." Annals of biomedical engineering 45.6 (June 2017): 1387-1398.
Website
http://hdl.handle.net/10161/15360
PMID
28361182
Source
epmc
Published In
Annals of Biomedical Engineering
Volume
45
Issue
6
Publish Date
2017
Start Page
1387
End Page
1398
DOI
10.1007/s10439-017-1822-8

Encapsulation of Adenovirus BMP2-Transduced Cells with PEGDA Hydrogels Allows Bone Formation in the Presence of Immune Response.

Gene therapy approaches have been difficult to implement due to pre-existing immunity against the virus used for delivery. To circumvent this problem, a cell-based approach was developed that avoided the use of free virus within the animal. However, even cells transduced in vitro with E1- to E3-deleted adenovirus encoding bone morphogenetic protein 2 (AdBMP2) resulted in the production of virus-neutralizing antibodies in mice. Furthermore, when mice received an intramuscular injection of nonencoding adenovirus (AdEmpty)-transduced cells, AdBMP2-transduced cells were unable to launch bone formation when an intramuscular injection of these BMP2-producing cells was delivered 1 week later. This phenomenon was not observed in NOD/SCID mice, and could be overcome in C57BL/6 mice by encapsulating the adenovirus-transduced cells in a nondegradable hydrogel poly(ethylene glycol) diacrylate (PEGDA). Data collectively suggest that PEGDA hydrogel encapsulation of AdBMP2-transduced cells prevents pre-existing immunity from suppressing BMP2-induced bone formation.

Authors
Alvarez-Urena, P; Davis, E; Sonnet, C; Henslee, G; Gugala, Z; Strecker, EV; Linscheid, LJ; Cuchiara, M; West, J; Davis, A; Olmsted-Davis, E
MLA Citation
Alvarez-Urena, P, Davis, E, Sonnet, C, Henslee, G, Gugala, Z, Strecker, EV, Linscheid, LJ, Cuchiara, M, West, J, Davis, A, and Olmsted-Davis, E. "Encapsulation of Adenovirus BMP2-Transduced Cells with PEGDA Hydrogels Allows Bone Formation in the Presence of Immune Response." Tissue engineering. Part A 23.5-6 (March 2017): 177-184.
PMID
27967655
Source
epmc
Published In
Tissue Engineering, Part A
Volume
23
Issue
5-6
Publish Date
2017
Start Page
177
End Page
184
DOI
10.1089/ten.tea.2016.0277

Adhesive Peptide Sequences Regulate Valve Interstitial Cell Adhesion, Phenotype and Extracellular Matrix Deposition.

Knowledge of how extracellular matrix (ECM) binding impacts valve interstitial cells (VICs) is critical not only to better understanding the etiology of valvular diseases but also to constructing living valve substitutes that can grow and remodel. Use of ECM-mimicking adhesive peptides with specific affinity to different receptors provides insights into adhesion-mediated cell signaling and downstream outcomes. Expression of adhesion receptors by VICs was assessed by flow cytometry and used to guide the choice of peptides studied. The peptide RGDS with affinity to multiple integrin receptors, and specific receptor-targeting peptides DGEA (integrin α2β1), YIGSR (67kDa laminin/elastin receptor; 67LR), and VAPG (67LR) were incorporated into hydrogels to investigate their effects on VICs. DGEA, YIGSR, and VAPG alone were insufficient to induce stable VIC adhesion. As a result, these peptides were studied in combination with 1 mM RGDS. For VICs cultured on two-dimensional hydrogel surfaces, YIGSR and VAPG down-regulated the expression of smooth muscle α-actin (myofibroblast activation marker); DGEA promoted VIC adhesion and VIC-mediated ECM deposition and inhibited the activity of alkaline phosphatase (osteogenic differentiation marker). Further, YIGSR and DGEA in combination promoted ECM deposition while inhibiting both myofibroblastic and osteogenic differentiation. However, VICs behaved differently to adhesive ligands when cultured within three-dimensional hydrogels, with most VICs assuming a healthy, quiescent phenotype under all peptide conditions tested. DGEA promoted ECM deposition by VICs within hydrogels. Overall, we demonstrate that the presentation of defined peptides targeting specific adhesion receptors can be used to regulate VIC adhesion, phenotype and ECM synthesis.

Authors
Wu, Y; Grande-Allen, KJ; West, JL
MLA Citation
Wu, Y, Grande-Allen, KJ, and West, JL. "Adhesive Peptide Sequences Regulate Valve Interstitial Cell Adhesion, Phenotype and Extracellular Matrix Deposition." Cellular and molecular bioengineering 9.4 (December 2016): 479-495.
PMID
28220141
Source
epmc
Published In
Cellular and Molecular Bioengineering
Volume
9
Issue
4
Publish Date
2016
Start Page
479
End Page
495
DOI
10.1007/s12195-016-0451-x

Electrospun Polyurethane and Hydrogel Composite Scaffolds as Biomechanical Mimics for Aortic Valve Tissue Engineering

Authors
Puperi, DS; Kishan, A; Punske, ZE; Wu, Y; Cosgriff-Hernandez, E; West, JL; Grande-Allen, KJ
MLA Citation
Puperi, DS, Kishan, A, Punske, ZE, Wu, Y, Cosgriff-Hernandez, E, West, JL, and Grande-Allen, KJ. "Electrospun Polyurethane and Hydrogel Composite Scaffolds as Biomechanical Mimics for Aortic Valve Tissue Engineering." ACS Biomaterials Science & Engineering 2.9 (September 12, 2016): 1546-1558.
Source
crossref
Published In
ACS biomaterials science & engineering
Volume
2
Issue
9
Publish Date
2016
Start Page
1546
End Page
1558
DOI
10.1021/acsbiomaterials.6b00309

A 3D Poly(ethylene glycol)-based Tumor Angiogenesis Model to Study the Influence of Vascular Cells on Lung Tumor Cell Behavior.

Tumor angiogenesis is critical to tumor growth and metastasis, yet much is unknown about the role vascular cells play in the tumor microenvironment. In vitro models that mimic in vivo tumor neovascularization facilitate exploration of this role. Here we investigated lung adenocarcinoma cancer cells (344SQ) and endothelial and pericyte vascular cells encapsulated in cell-adhesive, proteolytically-degradable poly(ethylene) glycol-based hydrogels. 344SQ in hydrogels formed spheroids and secreted proangiogenic growth factors that significantly increased with exposure to transforming growth factor beta 1 (TGF-β1), a potent tumor progression-promoting factor. Vascular cells in hydrogels formed tubule networks with localized activated TGF-β1. To study cancer cell-vascular cell interactions, we engineered a 2-layer hydrogel with 344SQ and vascular cell layers. Large, invasive 344SQ clusters (area > 5,000 μm(2), circularity < 0.25) developed at the interface between the layers, and were not evident further from the interface or in control hydrogels without vascular cells. A modified model with spatially restricted 344SQ and vascular cell layers confirmed that observed cluster morphological changes required close proximity to vascular cells. Additionally, TGF-β1 inhibition blocked endothelial cell-driven 344SQ migration. Our findings suggest vascular cells contribute to tumor progression and establish this culture system as a platform for studying tumor vascularization.

Authors
Roudsari, LC; Jeffs, SE; Witt, AS; Gill, BJ; West, JL
MLA Citation
Roudsari, LC, Jeffs, SE, Witt, AS, Gill, BJ, and West, JL. "A 3D Poly(ethylene glycol)-based Tumor Angiogenesis Model to Study the Influence of Vascular Cells on Lung Tumor Cell Behavior." Scientific reports 6 (September 6, 2016): 32726-.
PMID
27596933
Source
epmc
Published In
Scientific Reports
Volume
6
Publish Date
2016
Start Page
32726
DOI
10.1038/srep32726

Fabrication of 3D Biomimetic Microfluidic Networks in Hydrogels.

A laser-based hydrogel degradation technique is developed that allows for local control over hydrogel porosity, fabrication of 3D vascular-derived, biomimetic, hydrogel-embedded microfluidic networks, and generation of two intertwining, yet independent, microfluidic networks in a single construct.

Authors
Heintz, KA; Bregenzer, ME; Mantle, JL; Lee, KH; West, JL; Slater, JH
MLA Citation
Heintz, KA, Bregenzer, ME, Mantle, JL, Lee, KH, West, JL, and Slater, JH. "Fabrication of 3D Biomimetic Microfluidic Networks in Hydrogels." Advanced healthcare materials 5.17 (September 2016): 2153-2160.
PMID
27239785
Source
epmc
Published In
Advanced healthcare materials
Volume
5
Issue
17
Publish Date
2016
Start Page
2153
End Page
2160
DOI
10.1002/adhm.201600351

Biomimetic Microfluidic Networks: Fabrication of 3D Biomimetic Microfluidic Networks in Hydrogels (Adv. Healthcare Mater. 17/2016)

Authors
Heintz, KA; Bregenzer, ME; Mantle, JL; Lee, KH; West, JL; Slater, JH
MLA Citation
Heintz, KA, Bregenzer, ME, Mantle, JL, Lee, KH, West, JL, and Slater, JH. "Biomimetic Microfluidic Networks: Fabrication of 3D Biomimetic Microfluidic Networks in Hydrogels (Adv. Healthcare Mater. 17/2016)." Advanced Healthcare Materials 5.17 (September 2016): 2152-2152.
Source
crossref
Published In
Advanced healthcare materials
Volume
5
Issue
17
Publish Date
2016
Start Page
2152
End Page
2152
DOI
10.1002/adhm.201670093

Biomimetic Surface Patterning Promotes Mesenchymal Stem Cell Differentiation.

Both chemical and mechanical stimuli can dramatically influence cell behavior. By optimizing the signals cells experience, it may be possible to control the behavior of therapeutic cell populations. In this work, biomimetic geometries of adhesive ligands, which recapitulate the morphology of mature cells, are used to direct human mesenchymal stem cell (HMSC) differentiation toward a desired lineage. Specifically, adipocytes cultured in 2D are imaged and used to develop biomimetic virtual masks used in laser scanning lithography to form patterned fibronectin surfaces. The impact of adipocyte-derived pattern geometry on HMSC differentiation is compared to the behavior of HMSCs cultured on square and circle geometries, as well as adipocyte-derived patterns modified to include high stress regions. HMSCs on adipocyte mimetic geometries demonstrate greater adipogenesis than HMSCs on the other patterns. Greater than 45% of all HMSCs cultured on adipocyte mimetic patterns underwent adipogenesis as compared to approximately 19% of cells on modified adipocyte patterns with higher stress regions. These results are attributed to variations in cytoskeletal tension experienced by cells on the different protein micropatterns. The effects of geometry on adipogenesis are mitigated by the incorporation of a cytoskeletal protein inhibitor; exposure to this inhibitor leads to increased adipogenesis on all patterns examined.

Authors
Shukla, A; Slater, JH; Culver, JC; Dickinson, ME; West, JL
MLA Citation
Shukla, A, Slater, JH, Culver, JC, Dickinson, ME, and West, JL. "Biomimetic Surface Patterning Promotes Mesenchymal Stem Cell Differentiation." ACS applied materials & interfaces 8.34 (August 2016): 21883-21892.
PMID
26674708
Source
epmc
Published In
ACS Applied Materials and Interfaces
Volume
8
Issue
34
Publish Date
2016
Start Page
21883
End Page
21892
DOI
10.1021/acsami.5b08978

Hyaluronan Hydrogels for a Biomimetic Spongiosa Layer of Tissue Engineered Heart Valve Scaffolds.

Advanced tissue engineered heart valves must be constructed from multiple materials to better mimic the heterogeneity found in the native valve. The trilayered structure of aortic valves provides the ability to open and close consistently over a full human lifetime, with each layer performing specific mechanical functions. The middle spongiosa layer consists primarily of proteoglycans and glycosaminoglycans, providing lubrication and dampening functions as the valve leaflet flexes open and closed. In this study, hyaluronan hydrogels were tuned to perform the mechanical functions of the spongiosa layer, provide a biomimetic scaffold in which valve cells were encapsulated in 3D for tissue engineering applications, and gain insight into how valve cells maintain hyaluronan homeostasis within heart valves. Expression of the HAS1 isoform of hyaluronan synthase was significantly higher in hyaluronan hydrogels compared to blank-slate poly(ethylene glycol) diacrylate (PEGDA) hydrogels. Hyaluronidase and matrix metalloproteinase enzyme activity was similar between hyaluronan and PEGDA hydrogels, even though these scaffold materials were each specifically susceptible to degradation by different enzyme types. KIAA1199 was expressed by valve cells and may play a role in the regulation of hyaluronan in heart valves. Cross-linked hyaluronan hydrogels maintained healthy phenotype of valve cells in 3D culture and were tuned to approximate the mechanical properties of the valve spongiosa layer. Therefore, hyaluronan can be used as an appropriate material for the spongiosa layer of a proposed laminate tissue engineered heart valve scaffold.

Authors
Puperi, DS; O'Connell, RW; Punske, ZE; Wu, Y; West, JL; Grande-Allen, KJ
MLA Citation
Puperi, DS, O'Connell, RW, Punske, ZE, Wu, Y, West, JL, and Grande-Allen, KJ. "Hyaluronan Hydrogels for a Biomimetic Spongiosa Layer of Tissue Engineered Heart Valve Scaffolds." Biomacromolecules 17.5 (May 2016): 1766-1775.
PMID
27120017
Source
epmc
Published In
Biomacromolecules
Volume
17
Issue
5
Publish Date
2016
Start Page
1766
End Page
1775
DOI
10.1021/acs.biomac.6b00180

Bioactive poly(ethylene glycol) hydrogels to recapitulate the HSC niche and facilitate HSC expansion in culture.

Hematopoietic stem cells (HSCs) have been used therapeutically for decades, yet their widespread clinical use is hampered by the inability to expand HSCs successfully in vitro. In culture, HSCs rapidly differentiate and lose their ability to self-renew. We hypothesize that by mimicking aspects of the bone marrow microenvironment in vitro we can better control the expansion and differentiation of these cells. In this work, derivatives of poly(ethylene glycol) diacrylate hydrogels were used as a culture substrate for hematopoietic stem and progenitor cell (HSPC) populations. Key HSC cytokines, stem cell factor (SCF) and interferon-γ (IFNγ), as well as the cell adhesion ligands RGDS and connecting segment 1 were covalently immobilized onto the surface of the hydrogels. With the use of SCF and IFNγ, we observed significant expansion of HSPCs, ∼97 and ∼104 fold respectively, while maintaining c-kit(+) lin(-) and c-kit(+) Sca1(+) lin(-) (KSL) populations and the ability to form multilineage colonies after 14 days. HSPCs were also encapsulated within degradable poly(ethylene glycol) hydrogels for three-dimensional culture. After expansion in hydrogels, ∼60% of cells were c-kit(+), demonstrating no loss in the proportion of these cells over the 14 day culture period, and ∼50% of colonies formed were multilineage, indicating that the cells retained their differentiation potential. The ability to tailor and use this system to support HSC growth could have implications on the future use of HSCs and other blood cell types in a clinical setting.

Authors
Cuchiara, ML; Coşkun, S; Banda, OA; Horter, KL; Hirschi, KK; West, JL
MLA Citation
Cuchiara, ML, Coşkun, S, Banda, OA, Horter, KL, Hirschi, KK, and West, JL. "Bioactive poly(ethylene glycol) hydrogels to recapitulate the HSC niche and facilitate HSC expansion in culture." Biotechnology and bioengineering 113.4 (April 2016): 870-881.
PMID
26497172
Source
epmc
Published In
Biotechnology & Bioengineering
Volume
113
Issue
4
Publish Date
2016
Start Page
870
End Page
881
DOI
10.1002/bit.25848

Poly(ethylene glycol) Hydrogel Scaffolds Containing Cell-Adhesive and Protease-Sensitive Peptides Support Microvessel Formation by Endothelial Progenitor Cells.

The development of stable, functional microvessels remains an important obstacle to overcome for tissue engineered organs and treatment of ischemia. Endothelial progenitor cells (EPCs) are a promising cell source for vascular tissue engineering as they are readily obtainable and carry the potential to differentiate towards all endothelial phenotypes. The aim of this study was to investigate the ability of human umbilical cord blood-derived EPCs to form vessel-like structures within a tissue engineering scaffold material, a cell-adhesive and proteolytically degradable poly(ethylene glycol) (PEG) hydrogel. EPCs in co-culture with angiogenic mural cells were encapsulated in hydrogel scaffolds by mixing with polymeric precursors and using a mild photocrosslinking process to form hydrogels with homogeneously dispersed cells. EPCs formed 3D microvessels networks that were stable for at least 30 days in culture, without the need for supplemental angiogenic growth factors. These 3D EPC microvessels displayed aspects of physiological microvasculature with lumen formation, expression of endothelial cell proteins (connexin 32, VE-cadherin, eNOS), basement membrane formation with collagen IV and laminin, perivascular investment of PDGFR-β and α-SMA positive cells, and EPC quiescence (<1% proliferating cells) by 2 weeks of co-culture. Our findings demonstrate the development of a novel, reductionist system that is well-defined and reproducible for studying progenitor cell-driven microvessel formation.

Authors
Peters, EB; Christoforou, N; Leong, KW; Truskey, GA; West, JL
MLA Citation
Peters, EB, Christoforou, N, Leong, KW, Truskey, GA, and West, JL. "Poly(ethylene glycol) Hydrogel Scaffolds Containing Cell-Adhesive and Protease-Sensitive Peptides Support Microvessel Formation by Endothelial Progenitor Cells." Cellular and molecular bioengineering 9.1 (March 2016): 38-54.
PMID
27042236
Source
epmc
Published In
Cellular and Molecular Bioengineering
Volume
9
Issue
1
Publish Date
2016
Start Page
38
End Page
54
DOI
10.1007/s12195-015-0423-6

Cancer-Associated Fibroblasts Induce a Collagen Cross-link Switch in Tumor Stroma.

Intratumoral collagen cross-links heighten stromal stiffness and stimulate tumor cell invasion, but it is unclear how collagen cross-linking is regulated in epithelial tumors. To address this question, we used Kras(LA1) mice, which develop lung adenocarcinomas from somatic activation of a Kras(G12D) allele. The lung tumors in Kras(LA1) mice were highly fibrotic and contained cancer-associated fibroblasts (CAF) that produced collagen and generated stiffness in collagen gels. In xenograft tumors generated by injection of wild-type mice with lung adenocarcinoma cells alone or in combination with CAFs, the total concentration of collagen cross-links was the same in tumors generated with or without CAFs, but coinjected tumors had higher hydroxylysine aldehyde-derived collagen cross-links (HLCC) and lower lysine-aldehyde-derived collagen cross-links (LCCs). Therefore, we postulated that an LCC-to-HLCC switch induced by CAFs promotes the migratory and invasive properties of lung adenocarcinoma cells. To test this hypothesis, we created coculture models in which CAFs are positioned interstitially or peripherally in tumor cell aggregates, mimicking distinct spatial orientations of CAFs in human lung cancer. In both contexts, CAFs enhanced the invasive properties of tumor cells in three-dimensional (3D) collagen gels. Tumor cell aggregates that attached to CAF networks on a Matrigel surface dissociated and migrated on the networks. Lysyl hydroxylase 2 (PLOD2/LH2), which drives HLCC formation, was expressed in CAFs, and LH2 depletion abrogated the ability of CAFs to promote tumor cell invasion and migration.CAFs induce a collagen cross-link switch in tumor stroma to influence the invasive properties of tumor cells.

Authors
Pankova, D; Chen, Y; Terajima, M; Schliekelman, MJ; Baird, BN; Fahrenholtz, M; Sun, L; Gill, BJ; Vadakkan, TJ; Kim, MP; Ahn, Y-H; Roybal, JD; Liu, X; Parra Cuentas, ER; Rodriguez, J; Wistuba, II; Creighton, CJ; Gibbons, DL; Hicks, JM; Dickinson, ME; West, JL; Grande-Allen, KJ; Hanash, SM; Yamauchi, M; Kurie, JM
MLA Citation
Pankova, D, Chen, Y, Terajima, M, Schliekelman, MJ, Baird, BN, Fahrenholtz, M, Sun, L, Gill, BJ, Vadakkan, TJ, Kim, MP, Ahn, Y-H, Roybal, JD, Liu, X, Parra Cuentas, ER, Rodriguez, J, Wistuba, II, Creighton, CJ, Gibbons, DL, Hicks, JM, Dickinson, ME, West, JL, Grande-Allen, KJ, Hanash, SM, Yamauchi, M, and Kurie, JM. "Cancer-Associated Fibroblasts Induce a Collagen Cross-link Switch in Tumor Stroma." Molecular cancer research : MCR 14.3 (March 2016): 287-295.
PMID
26631572
Source
epmc
Published In
Molecular cancer research : MCR
Volume
14
Issue
3
Publish Date
2016
Start Page
287
End Page
295
DOI
10.1158/1541-7786.mcr-15-0307

Studying the influence of angiogenesis in in vitro cancer model systems.

Tumor angiogenesis is a hallmark of cancer that has been identified as a critical component of cancer progression, facilitating rapid tumor growth and metastasis. Anti-angiogenic therapies have exhibited only modest clinical success, highlighting a need for better models that can be used to gain a more thorough understanding of tumor angiogenesis and screen potential therapeutics more accurately. This review explores how recent progress in in vitro cancer and vascular models individually can be applied to the development of in vitro tumor angiogenesis models. Current in vitro tumor angiogenesis models are also discussed, with a focus on aspects of the process that have been successfully recapitulated and opportunities for applying new technologies to expand model complexity to better represent the tumor microenvironment. Continued advances in vascularized tumor models will provide tools to identify novel therapeutic targets and validate their therapeutic benefit.

Authors
Roudsari, LC; West, JL
MLA Citation
Roudsari, LC, and West, JL. "Studying the influence of angiogenesis in in vitro cancer model systems." Advanced drug delivery reviews 97 (February 2016): 250-259. (Review)
PMID
26571106
Source
epmc
Published In
Advanced Drug Delivery Reviews
Volume
97
Publish Date
2016
Start Page
250
End Page
259
DOI
10.1016/j.addr.2015.11.004

A dual energy CT study on vascular effects of gold nanoparticles in radiation therapy

© 2016 SPIE. Gold nanoparticles (AuNPs) are emerging as promising agents for both cancer therapy and CT imaging. AuNPs are delivered to tumors via the enhanced permeability and retention effect and they preferentially accumulate in close proximity to the tumor blood vessels. AuNPs produce low-energy, short-range photoelectrons during external beam radiation therapy (RT), boosting dose. This work is focused on understanding how tumor vascular permeability is influenced by AuNP-augmented radiation therapy (RT), and how this knowledge can potentially improve the delivery of additional nanoparticle-based chemotherapeutics. We use dual energy (DE) CT to detect accumulation of AuNPs and increased vascular permeability to liposomal iodine (i.e. a surrogate for chemotherapeutics with liposome encapsulation) following RT. We used sarcoma tumors generated in LSL-Kras G12D ; p53 FL/FL conditional mutant mice. A total of n=37 mice were used in this study. The treated mice were injected with 20 mg AuNP (0.1 ml/25 g mouse) 24 hours before delivery of 5 Gy RT (n=5), 10 Gy RT (n=3) or 20 Gy RT (n=6). The control mice received no AuNP injection and either no RT (n=6), 5 Gy RT (n=3), 10 Gy RT (n=3), 20 Gy RT (n=1 1) . Twenty four hours post-RT, the mice were injected with liposomal iodine (0.3 ml/25 mouse) and imaged with DE-CT three days later. The results suggest that independent of any AuNP usage, RT levels of 10 Gy and 20 Gy increase the permeability of tumor vasculature to liposomal iodine and that the increase in permeability is dose-dependent. We found that the effect of RT on vasculature may already be at its maximum response i.e. saturated at 20 Gy, and therefore the addition of AuNPs had almost no added benefit. Similarly, at 5 Gy RT, our data suggests that there was no effect of AuNP augmentation on tumor vascular permeability. However, b y using AuNPs with 10 Gy RT, we observed an increase in the vascular permeability, however this is not yet statistically significant due to the small number of mice in these groups. Such an approach can be used together with a liposomal drug delivery system to increase specific tumor delivery of chemotherapeutics. Our method has the potential to significantly improve tumor therapy and reduce the side effects from both RT and chemotherapy.

Authors
Ashton, JR; Hoye, J; Deland, K; Whitley, M; Qi, Y; Moding, E; Kirsch, DG; West, J; Badea, CT
MLA Citation
Ashton, JR, Hoye, J, Deland, K, Whitley, M, Qi, Y, Moding, E, Kirsch, DG, West, J, and Badea, CT. "A dual energy CT study on vascular effects of gold nanoparticles in radiation therapy." January 1, 2016.
Source
scopus
Published In
Proceedings of SPIE
Volume
9788
Publish Date
2016
DOI
10.1117/12.2217012

Hydrogels and Angiogenesis

Authors
West, JL; Nsiah, BN; Moore, E; Ali, S
MLA Citation
West, JL, Nsiah, BN, Moore, E, and Ali, S. "Hydrogels and Angiogenesis." Biosynthetic Polymers for Medical Applications. Ed. L Poole-Warren, P Martens, and R Green. Elsevier, November 26, 2015. (Chapter)
Source
manual
Publish Date
2015

Angiogenesis in hydrogel biomaterials

© 2016 Elsevier Ltd. All rights reserved. Our ever-improving understanding of the cellular and molecular processes involved in angiogenesis enables increasingly sophisticated design of pro-angiogenic biomaterials. More complex interactions may be required for formation of optimally functional vasculature. Engineered microvasculature in hydrogel biomaterials may also have far-reaching impacts on the development of optimised culture systems for a variety of stem cells. In vivo, many stem cell niches are closely associated with microvasculature, and these associations have been shown to be critical to the maintenance of stem cells in the niche microenvironment.

Authors
Nsiah, BA; Moore, EM; Roudsari, LC; Virdone, NK; West, JL
MLA Citation
Nsiah, BA, Moore, EM, Roudsari, LC, Virdone, NK, and West, JL. "Angiogenesis in hydrogel biomaterials." Biosynthetic Polymers for Medical Applications. November 24, 2015. 189-203.
Source
scopus
Publish Date
2015
Start Page
189
End Page
203
DOI
10.1016/B978-1-78242-105-4.00008-0

Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro.

Umbilical cord blood represents a promising cell source for pro-angiogenic therapies. The present study examined the potential of mononuclear cells (MNCs) from umbilical cord blood to support endothelial progenitor cell (EPC) microvessel formation. MNCs were isolated from the cord blood of 20 separate donors and selected for further characterization based upon their proliferation potential and morphological resemblance to human vascular pericytes (HVPs). MNCs were screened for their ability to support EPC network formation using an in vitro assay (Matrigel™) as well as a reductionist, coculture system consisting of no additional angiogenic cytokines beyond those present in serum. In less than 15% of the isolations, we identified a population of highly proliferative MNCs that phenotypically resembled HVPs as assessed by expression of PDGFR-β, NG2, α-SMA, and ephrin-B2. Within a Matrigel™ system, MNCs demonstrated pericyte-like function through colocalization to EPC networks and similar effects as HVPs upon total EPC tubule length (p = 0.95) and number of branch points (p = 0.93). In a reductionist coculture system, MNCs served as pro-angiogenic mural cells by supporting EPC network formation to a significantly greater extent than HVP cocultures, by day 14 of coculture, as evidenced through EPC total tubule length (p < 0.0001) and number of branch points (p < 0.0001). Our findings are significant as we demonstrate mural cell progenitors can be isolated from umbilical cord blood and develop culture conditions to support their use in microvascular tissue engineering applications.

Authors
Peters, EB; Liu, B; Christoforou, N; West, JL; Truskey, GA
MLA Citation
Peters, EB, Liu, B, Christoforou, N, West, JL, and Truskey, GA. "Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro." Annals of biomedical engineering 43.10 (October 2015): 2552-2568.
PMID
25777295
Source
epmc
Published In
Annals of Biomedical Engineering
Volume
43
Issue
10
Publish Date
2015
Start Page
2552
End Page
2568
DOI
10.1007/s10439-015-1301-z

3-Dimensional spatially organized PEG-based hydrogels for an aortic valve co-culture model.

Physiologically relevant in vitro models are needed to study disease progression and to develop and screen potential therapeutic interventions for disease. Heart valve disease, in particular, has no early intervention or non-invasive treatment because there is a lack of understanding the cellular mechanisms which lead to disease. Here, we establish a novel, customizable synthetic hydrogel platform that can be used to study cell-cell interactions and the factors which contribute to valve disease. Spatially localized cell adhesive ligands bound in the scaffold promote cell growth and organization of valve interstitial cells and valve endothelial cells in 3D co-culture. Both cell types maintained phenotypes, homeostatic functions, and produced zonally localized extracellular matrix. This model extends the capabilities of in vitro research by providing a platform to perform direct contact co-culture with cells in their physiologically relevant spatial arrangement.

Authors
Puperi, DS; Balaoing, LR; O'Connell, RW; West, JL; Grande-Allen, KJ
MLA Citation
Puperi, DS, Balaoing, LR, O'Connell, RW, West, JL, and Grande-Allen, KJ. "3-Dimensional spatially organized PEG-based hydrogels for an aortic valve co-culture model." Biomaterials 67 (October 2015): 354-364.
PMID
26241755
Source
epmc
Published In
Biomaterials
Volume
67
Publish Date
2015
Start Page
354
End Page
364
DOI
10.1016/j.biomaterials.2015.07.039

Erratum to: Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro.

Authors
Peters, EB; Liu, B; Christoforou, N; West, JL; Truskey, GA
MLA Citation
Peters, EB, Liu, B, Christoforou, N, West, JL, and Truskey, GA. "Erratum to: Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro." Annals of biomedical engineering 43.8 (August 2015): 2022-.
PMID
25877461
Source
epmc
Published In
Annals of Biomedical Engineering
Volume
43
Issue
8
Publish Date
2015
Start Page
2022
DOI
10.1007/s10439-015-1321-8

Hydrogel-Coated Near Infrared Absorbing Nanoshells as Light-Responsive Drug Delivery Vehicles.

Nanoparticle drug delivery carriers that can modulate drug release based on an exogenous signal, such as light, are of great interest, especially for improving cancer therapy. A light-activated delivery vehicle was fabricated by synthesizing a thin, thermally responsive poly(N-isopropylacrylamide-co-acrylamide) hydrogel coating directly onto the surfaces of individual near-infrared (NIR) absorbing gold-silica nanoshells. This hydrogel was designed to be in a swollen state under physiological conditions and expel large amounts of water, along with any entrapped drug, at elevated temperatures. The required temperature change can be achieved via NIR absorption by the nanoshell, allowing the hydrogel phase change to be triggered by light, which was observed by monitoring changes in particle sizes as water was expelled from the hydrogel network. The phase change was reversible and repeatable. As a model drug, the chemotherapeutic doxorubicin was loaded into this delivery vehicle, and rapid release of doxorubicin occurred upon NIR exposure. Further, colon carcinoma cells exposed to the irradiated platform displayed nearly 3 times as much doxorubicin uptake as cells exposed to nonirradiated particles or free drug, which in turn resulted in a higher loss of cell viability. We hypothesize these effects are because the NIR-mediated heating results in a transient increase in cell membrane permeability, thus aiding in cellular uptake of the drug.

Authors
Strong, LE; West, JL
MLA Citation
Strong, LE, and West, JL. "Hydrogel-Coated Near Infrared Absorbing Nanoshells as Light-Responsive Drug Delivery Vehicles." ACS biomaterials science & engineering 1.8 (August 2015): 685-692.
PMID
26366438
Source
epmc
Published In
ACS biomaterials science & engineering
Volume
1
Issue
8
Publish Date
2015
Start Page
685
End Page
692

Erratum

MLA Citation
"Erratum." Therapeutic Delivery 6.7 (July 2015): 888-888.
Source
crossref
Published In
Therapeutic delivery
Volume
6
Issue
7
Publish Date
2015
Start Page
888
End Page
888
DOI
10.4155/tde.15.50

Recapitulation and Modulation of the Cellular Architecture of a User-Chosen Cell of Interest Using Cell-Derived, Biomimetic Patterning.

Heterogeneity of cell populations can confound population-averaged measurements and obscure important findings or foster inaccurate conclusions. The ability to generate a homogeneous cell population, at least with respect to a chosen trait, could significantly aid basic biological research and development of high-throughput assays. Accordingly, we developed a high-resolution, image-based patterning strategy to produce arrays of single-cell patterns derived from the morphology or adhesion site arrangement of user-chosen cells of interest (COIs). Cells cultured on both cell-derived patterns displayed a cellular architecture defined by their morphology, adhesive state, cytoskeletal organization, and nuclear properties that quantitatively recapitulated the COIs that defined the patterns. Furthermore, slight modifications to pattern design allowed for suppression of specific actin stress fibers and direct modulation of adhesion site dynamics. This approach to patterning provides a strategy to produce a more homogeneous cell population, decouple the influences of cytoskeletal structure, adhesion dynamics, and intracellular tension on mechanotransduction-mediated processes, and a platform for high-throughput cellular assays.

Authors
Slater, JH; Culver, JC; Long, BL; Hu, CW; Hu, J; Birk, TF; Qutub, AA; Dickinson, ME; West, JL
MLA Citation
Slater, JH, Culver, JC, Long, BL, Hu, CW, Hu, J, Birk, TF, Qutub, AA, Dickinson, ME, and West, JL. "Recapitulation and Modulation of the Cellular Architecture of a User-Chosen Cell of Interest Using Cell-Derived, Biomimetic Patterning." ACS nano 9.6 (June 2015): 6128-6138.
PMID
25988713
Source
epmc
Published In
ACS Nano
Volume
9
Issue
6
Publish Date
2015
Start Page
6128
End Page
6138
DOI
10.1021/acsnano.5b01366

Optical coherence tomography guided microinjections in live mouse embryos: high-resolution targeted manipulation for mouse embryonic research.

The ability to conduct highly localized delivery of contrast agents, viral vectors, therapeutic or pharmacological agents, and signaling molecules or dyes to live mammalian embryos is greatly desired to enable a variety of studies in the field of developmental biology, such as investigating the molecular regulation of cardiovascular morphogenesis. To meet such a demand, we introduce, for the first time, the concept of employing optical coherence tomography (OCT)-guide microinjections in live mouse embryos, which provides precisely targeted manipulation with spatial resolution at the micrometer scale. The feasibility demonstration is performed with experimental studies on cultured live mouse embryos at E8.5 and E9.5. Additionally, we investigate the OCT-guided microinjection of gold–silica nanoshells to the yolk sac vasculature of live cultured mouse embryos at the stage when the heart just starts to beat, as a potential approach for dynamic assessment of cardiovascular form and function before the onset of blood cell circulation. Also, the capability of OCT to quantitatively monitor and measure injection volume is presented. Our results indicate that OCT-guided microinjection could be a useful tool for mouse embryonic research.

Authors
Syed, SH; Coughlin, AJ; Garcia, MD; Wang, S; West, JL; Larin, KV; Larina, IV
MLA Citation
Syed, SH, Coughlin, AJ, Garcia, MD, Wang, S, West, JL, Larin, KV, and Larina, IV. "Optical coherence tomography guided microinjections in live mouse embryos: high-resolution targeted manipulation for mouse embryonic research." Journal of Biomedical Optics 20.5 (May 2015): 051020-.
PMID
25581495
Source
epmc
Published In
Journal of Biomedical Optics
Volume
20
Issue
5
Publish Date
2015
Start Page
051020
DOI
10.1117/1.jbo.20.5.051020

Encoding Hydrogel Mechanics via Network Cross-Linking Structure.

The effects of mechanical cues on cell behaviors in 3D remain difficult to characterize as the ability to tune hydrogel mechanics often requires changes in the polymer density, potentially altering the material's biochemical and physical characteristics. Additionally, with most PEG diacrylate (PEGDA) hydrogels, forming materials with compressive moduli less than ∼10 kPa has been virtually impossible. Here, we present a new method of controlling the mechanical properties of PEGDA hydrogels independent of polymer chain density through the incorporation of additional vinyl group moieties that interfere with the cross-linking of the network. This modification can tune hydrogel mechanics in a concentration dependent manner from <1 to 17 kPa, a more physiologically relevant range than previously possible with PEG-based hydrogels, without altering the hydrogel's degradation and permeability. Across this range of mechanical properties, endothelial cells (ECs) encapsulated within MMP-2/MMP-9 degradable hydrogels with RGDS adhesive peptides revealed increased cell spreading as hydrogel stiffness decreased in contrast to behavior typically observed for cells on 2D surfaces. EC-pericyte cocultures exhibited vessel-like networks within 3 days in highly compliant hydrogels as compared to a week in stiffer hydrogels. These vessel networks persisted for at least 4 weeks and deposited laminin and collagen IV perivascularly. These results indicate that EC morphogenesis can be regulated using mechanical cues in 3D. Furthermore, controlling hydrogel compliance independent of density allows for the attainment of highly compliant mechanical regimes in materials that can act as customizable cell microenvironments.

Authors
Schweller, RM; West, JL
MLA Citation
Schweller, RM, and West, JL. "Encoding Hydrogel Mechanics via Network Cross-Linking Structure." ACS biomaterials science & engineering 1.5 (May 2015): 335-344.
PMID
26082943
Source
epmc
Published In
ACS biomaterials science & engineering
Volume
1
Issue
5
Publish Date
2015
Start Page
335
End Page
344
DOI
10.1021/acsbiomaterials.5b00064

Integrating valve-inspired design features into poly(ethylene glycol) hydrogel scaffolds for heart valve tissue engineering.

The development of advanced scaffolds that recapitulate the anisotropic mechanical behavior and biological functions of the extracellular matrix in leaflets would be transformative for heart valve tissue engineering. In this study, anisotropic mechanical properties were established in poly(ethylene glycol) (PEG) hydrogels by crosslinking stripes of 3.4 kDa PEG diacrylate (PEGDA) within 20 kDa PEGDA base hydrogels using a photolithographic patterning method. Varying the stripe width and spacing resulted in a tensile elastic modulus parallel to the stripes that was 4.1-6.8 times greater than that in the perpendicular direction, comparable to the degree of anisotropy between the circumferential and radial orientations in native valve leaflets. Biomimetic PEG-peptide hydrogels were prepared by tethering the cell-adhesive peptide RGDS and incorporating the collagenase-degradable peptide PQ (GGGPQG↓IWGQGK) into the polymer network. The specific amounts of RGDS and PEG-PQ within the resulting hydrogels influenced the elongation, de novo extracellular matrix deposition and hydrogel degradation behavior of encapsulated valvular interstitial cells (VICs). In addition, the morphology and activation of VICs grown atop PEG hydrogels could be modulated by controlling the concentration or micro-patterning profile of PEG-RGDS. These results are promising for the fabrication of PEG-based hydrogels using anatomically and biologically inspired scaffold design features for heart valve tissue engineering.

Authors
Zhang, X; Xu, B; Puperi, DS; Yonezawa, AL; Wu, Y; Tseng, H; Cuchiara, ML; West, JL; Grande-Allen, KJ
MLA Citation
Zhang, X, Xu, B, Puperi, DS, Yonezawa, AL, Wu, Y, Tseng, H, Cuchiara, ML, West, JL, and Grande-Allen, KJ. "Integrating valve-inspired design features into poly(ethylene glycol) hydrogel scaffolds for heart valve tissue engineering." Acta biomaterialia 14 (March 2015): 11-21.
PMID
25433168
Source
epmc
Published In
Acta Biomaterialia
Volume
14
Publish Date
2015
Start Page
11
End Page
21
DOI
10.1016/j.actbio.2014.11.042

Integrating valve-inspired design features into poly(ethylene glycol) hydrogel scaffolds for heart valve tissue engineering

© 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. The development of advanced scaffolds that recapitulate the anisotropic mechanical behavior and biological functions of the extracellular matrix in leaflets would be transformative for heart valve tissue engineering. In this study, anisotropic mechanical properties were established in poly(ethylene glycol) (PEG) hydrogels by crosslinking stripes of 3.4 kDa PEG diacrylate (PEGDA) within 20 kDa PEGDA base hydrogels using a photolithographic patterning method. Varying the stripe width and spacing resulted in a tensile elastic modulus parallel to the stripes that was 4.1-6.8 times greater than that in the perpendicular direction, comparable to the degree of anisotropy between the circumferential and radial orientations in native valve leaflets. Biomimetic PEG-peptide hydrogels were prepared by tethering the cell-adhesive peptide RGDS and incorporating the collagenase-degradable peptide PQ (GGGPQG;IWGQGK) into the polymer network. The specific amounts of RGDS and PEG-PQ within the resulting hydrogels influenced the elongation, de novo extracellular matrix deposition and hydrogel degradation behavior of encapsulated valvular interstitial cells (VICs). In addition, the morphology and activation of VICs grown atop PEG hydrogels could be modulated by controlling the concentration or micro-patterning profile of PEG-RGDS. These results are promising for the fabrication of PEG-based hydrogels using anatomically and biologically inspired scaffold design features for heart valve tissue engineering.

Authors
Zhang, X; Xu, B; Puperi, DS; Yonezawa, AL; Wu, Y; Tseng, H; Cuchiara, ML; West, JL; Grande-Allen, KJ
MLA Citation
Zhang, X, Xu, B, Puperi, DS, Yonezawa, AL, Wu, Y, Tseng, H, Cuchiara, ML, West, JL, and Grande-Allen, KJ. "Integrating valve-inspired design features into poly(ethylene glycol) hydrogel scaffolds for heart valve tissue engineering." Acta Biomaterialia 14 (January 1, 2015): 11-21.
Source
scopus
Published In
Acta Biomaterialia
Volume
14
Publish Date
2015
Start Page
11
End Page
21
DOI
10.1016/j.actbio.2014.11.042

Application of hydrogels in heart valve tissue engineering.

With an increasing number of patients requiring valve replacements, there is heightened interest in advancing heart valve tissue engineering (HVTE) to provide solutions to the many limitations of current surgical treatments. A variety of materials have been developed as scaffolds for HVTE including natural polymers, synthetic polymers, and decellularized valvular matrices. Among them, biocompatible hydrogels are generating growing interest. Natural hydrogels, such as collagen and fibrin, generally show good bioactivity but poor mechanical durability. Synthetic hydrogels, on the other hand, have tunable mechanical properties; however, appropriate cell-matrix interactions are difficult to obtain. Moreover, hydrogels can be used as cell carriers when the cellular component is seeded into the polymer meshes or decellularized valve scaffolds. In this review, we discuss current research strategies for HVTE with an emphasis on hydrogel applications. The physicochemical properties and fabrication methods of these hydrogels, as well as their mechanical properties and bioactivities are described. Performance of some hydrogels including in vitro evaluation using bioreactors and in vivo tests in different animal models are also discussed. For future HVTE, it will be compelling to examine how hydrogels can be constructed from composite materials to replicate mechanical properties and mimic biological functions of the native heart valve.

Authors
Zhang, X; Xu, B; Puperi, DS; Wu, Y; West, JL; Grande-Allen, KJ
MLA Citation
Zhang, X, Xu, B, Puperi, DS, Wu, Y, West, JL, and Grande-Allen, KJ. "Application of hydrogels in heart valve tissue engineering." Journal of long-term effects of medical implants 25.1-2 (January 2015): 105-134. (Review)
PMID
25955010
Source
epmc
Published In
Journal of Long-Term Effects of Medical Implants
Volume
25
Issue
1-2
Publish Date
2015
Start Page
105
End Page
134
DOI
10.1615/jlongtermeffmedimplants.2015011817

Optically modulated cancer therapeutic delivery: past, present and future.

Chemotherapeutic regimens are often restricted by dose-limiting toxicities that arise from drug exposure to off-site tissues. Nanoparticle drug carriers that specifically deliver therapeutics to the site of malignant tissue are being actively researched today. One strategy is to utilize materials that are light-responsive, such that the carrier can be triggered to release its drug payload at the distinct time and location of light exposure. This review discusses recent advances in the development of such light-responsive drug carriers. With continued optimization and in vivo validation, these approaches may offer novel treatment options for cancer management.

Authors
Strong, LE; West, JL
MLA Citation
Strong, LE, and West, JL. "Optically modulated cancer therapeutic delivery: past, present and future." Therapeutic delivery 6.5 (January 2015): 545-558. (Review)
PMID
26001172
Source
epmc
Published In
Therapeutic delivery
Volume
6
Issue
5
Publish Date
2015
Start Page
545
End Page
558
DOI
10.4155/tde.15.17

Improved Angiogenesis in Response to Localized Delivery of Macrophage-Recruiting Molecules.

Successful engineering of complex organs requires improved methods to promote rapid and stable vascularization of artificial tissue scaffolds. Toward this goal, tissue engineering strategies utilize the release of pro-angiogenic growth factors, alone or in combination, from biomaterials to induce angiogenesis. In this study we have used intravital microscopy to define key, dynamic cellular changes induced by the release of pro-angiogenic factors from polyethylene glycol diacrylate hydrogels transplanted in vivo. Our data show robust macrophage recruitment when the potent and synergistic angiogenic factors, PDGFBB and FGF2 were used as compared with VEGF alone and intravital imaging suggested roles for macrophages in endothelial tip cell migration and anastomosis, as well as pericyte-like behavior. Further data from in vivo experiments show that delivery of CSF1 with VEGF can dramatically improve the poor angiogenic response seen with VEGF alone. These studies show that incorporating macrophage-recruiting factors into the design of pro-angiogenic biomaterial scaffolds is a key strategy likely to be necessary for stable vascularization and survival of implanted artificial tissues.

Authors
Hsu, C-W; Poché, RA; Saik, JE; Ali, S; Wang, S; Yosef, N; Calderon, GA; Scott, L; Vadakkan, TJ; Larina, IV; West, JL; Dickinson, ME
MLA Citation
Hsu, C-W, Poché, RA, Saik, JE, Ali, S, Wang, S, Yosef, N, Calderon, GA, Scott, L, Vadakkan, TJ, Larina, IV, West, JL, and Dickinson, ME. "Improved Angiogenesis in Response to Localized Delivery of Macrophage-Recruiting Molecules." PloS one 10.7 (January 2015): e0131643-.
PMID
26132702
Source
epmc
Published In
PloS one
Volume
10
Issue
7
Publish Date
2015
Start Page
e0131643
DOI
10.1371/journal.pone.0131643

CD45+ Cells Present Within Mesenchymal Stem Cell Populations Affect Network Formation of Blood-Derived Endothelial Outgrowth Cells.

Mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) represent promising cell sources for angiogenic therapies. There are, however, conflicting reports regarding the ability of MSCs to support network formation of endothelial cells. The goal of this study was to assess the ability of human bone marrow-derived MSCs to support network formation of endothelial outgrowth cells (EOCs) derived from umbilical cord blood EPCs. We hypothesized that upon in vitro coculture, MSCs and EOCs promote a microenvironment conducive for EOC network formation without the addition of angiogenic growth supplements. EOC networks formed by coculture with MSCs underwent regression and cell loss by day 10 with a near 4-fold and 2-fold reduction in branch points and mean segment length, respectively, in comparison with networks formed by coculture vascular smooth muscle cell (SMC) cocultures. EOC network regression in MSC cocultures was not caused by lack of vascular endothelial growth factor (VEGF)-A or changes in TGF-β1 or Ang-2 supernatant concentrations in comparison with SMC cocultures. Removal of CD45+ cells from MSCs improved EOC network formation through a 2-fold increase in total segment length and number of branch points in comparison to unsorted MSCs by day 6. These improvements, however, were not sustained by day 10. CD45 expression in MSC cocultures correlated with EOC network regression with a 5-fold increase between day 6 and day 10 of culture. The addition of supplemental growth factors VEGF, fibroblastic growth factor-2, EGF, hydrocortisone, insulin growth factor-1, ascorbic acid, and heparin to MSC cocultures promoted stable EOC network formation over 2 weeks in vitro, without affecting CD45 expression, as evidenced by a lack of significant differences in total segment length (p=0.96). These findings demonstrate the ability of MSCs to support EOC network formation correlates with removal of CD45+ cells and improves upon the addition of soluble growth factors.

Authors
Peters, EB; Christoforou, N; Moore, E; West, JL; Truskey, GA
MLA Citation
Peters, EB, Christoforou, N, Moore, E, West, JL, and Truskey, GA. "CD45+ Cells Present Within Mesenchymal Stem Cell Populations Affect Network Formation of Blood-Derived Endothelial Outgrowth Cells." BioResearch open access 4.1 (January 2015): 75-88.
Website
http://hdl.handle.net/10161/10662
PMID
26309784
Source
epmc
Published In
BioResearch Open Access
Volume
4
Issue
1
Publish Date
2015
Start Page
75
End Page
88
DOI
10.1089/biores.2014.0029

In vivo small animal micro-CT using nanoparticle contrast agents.

Computed tomography (CT) is one of the most valuable modalities for in vivo imaging because it is fast, high-resolution, cost-effective, and non-invasive. Moreover, CT is heavily used not only in the clinic (for both diagnostics and treatment planning) but also in preclinical research as micro-CT. Although CT is inherently effective for lung and bone imaging, soft tissue imaging requires the use of contrast agents. For small animal micro-CT, nanoparticle contrast agents are used in order to avoid rapid renal clearance. A variety of nanoparticles have been used for micro-CT imaging, but the majority of research has focused on the use of iodine-containing nanoparticles and gold nanoparticles. Both nanoparticle types can act as highly effective blood pool contrast agents or can be targeted using a wide variety of targeting mechanisms. CT imaging can be further enhanced by adding spectral capabilities to separate multiple co-injected nanoparticles in vivo. Spectral CT, using both energy-integrating and energy-resolving detectors, has been used with multiple contrast agents to enable functional and molecular imaging. This review focuses on new developments for in vivo small animal micro-CT using novel nanoparticle probes applied in preclinical research.

Authors
Ashton, JR; West, JL; Badea, CT
MLA Citation
Ashton, JR, West, JL, and Badea, CT. "In vivo small animal micro-CT using nanoparticle contrast agents." Frontiers in pharmacology 6 (January 2015): 256-. (Review)
Website
http://hdl.handle.net/10161/10945
PMID
26581654
Source
epmc
Published In
Frontiers in Pharmacology
Volume
6
Publish Date
2015
Start Page
256
DOI
10.3389/fphar.2015.00256

Anisotropic poly(ethylene glycol)/polycaprolactone hydrogel-fiber composites for heart valve tissue engineering.

The recapitulation of the material properties and structure of the native aortic valve leaflet, specifically its anisotropy and laminate structure, is a major design goal for scaffolds for heart valve tissue engineering. Poly(ethylene glycol) (PEG) hydrogels are attractive scaffolds for this purpose as they are biocompatible, can be modified for their mechanical and biofunctional properties, and can be laminated. This study investigated augmenting PEG hydrogels with polycaprolactone (PCL) as an analog to the fibrosa to improve strength and introduce anisotropic mechanical behavior. However, due to its hydrophobicity, PCL must be modified prior to embedding within PEG hydrogels. In this study, PCL was electrospun (ePCL) and modified in three different ways, by protein adsorption (pPCL), alkali digestion (hPCL), and acrylation (aPCL). Modified PCL of all types maintained the anisotropic elastic moduli and yield strain of unmodified anisotropic ePCL. Composites of PEG and PCL (PPCs) maintained anisotropic elastic moduli, but aPCL and pPCL had isotropic yield strains. Overall, PPCs of all modifications had elastic moduli of 3.79±0.90 MPa and 0.46±0.21 MPa in the parallel and perpendicular directions, respectively. Valvular interstitial cells seeded atop anisotropic aPCL displayed an actin distribution aligned in the direction of the underlying fibers. The resulting scaffold combines the biocompatibility and tunable fabrication of PEG with the strength and anisotropy of ePCL to form a foundation for future engineered valve scaffolds.

Authors
Tseng, H; Puperi, DS; Kim, EJ; Ayoub, S; Shah, JV; Cuchiara, ML; West, JL; Grande-Allen, KJ
MLA Citation
Tseng, H, Puperi, DS, Kim, EJ, Ayoub, S, Shah, JV, Cuchiara, ML, West, JL, and Grande-Allen, KJ. "Anisotropic poly(ethylene glycol)/polycaprolactone hydrogel-fiber composites for heart valve tissue engineering." Tissue engineering. Part A 20.19-20 (October 2014): 2634-2645.
PMID
24712446
Source
epmc
Published In
Tissue Engineering, Part A
Volume
20
Issue
19-20
Publish Date
2014
Start Page
2634
End Page
2645
DOI
10.1089/ten.tea.2013.0397

3D biofabrication strategies for tissue engineering and regenerative medicine.

Over the past several decades, there has been an ever-increasing demand for organ transplants. However, there is a severe shortage of donor organs, and as a result of the increasing demand, the gap between supply and demand continues to widen. A potential solution to this problem is to grow or fabricate organs using biomaterial scaffolds and a person's own cells. Although the realization of this solution has been limited, the development of new biofabrication approaches has made it more realistic. This review provides an overview of natural and synthetic biomaterials that have been used for organ/tissue development. It then discusses past and current biofabrication techniques, with a brief explanation of the state of the art. Finally, the review highlights the need for combining vascularization strategies with current biofabrication techniques. Given the multitude of applications of biofabrication technologies, from organ/tissue development to drug discovery/screening to development of complex in vitro models of human diseases, these manufacturing technologies can have a significant impact on the future of medicine and health care.

Authors
Bajaj, P; Schweller, RM; Khademhosseini, A; West, JL; Bashir, R
MLA Citation
Bajaj, P, Schweller, RM, Khademhosseini, A, West, JL, and Bashir, R. "3D biofabrication strategies for tissue engineering and regenerative medicine." Annual review of biomedical engineering 16 (July 2014): 247-276. (Review)
PMID
24905875
Source
epmc
Published In
Annual Review of Biomedical Engineering
Volume
16
Publish Date
2014
Start Page
247
End Page
276
DOI
10.1146/annurev-bioeng-071813-105155

Modeling the tumor extracellular matrix: Tissue engineering tools repurposed towards new frontiers in cancer biology

Cancer progression is mediated by complex epigenetic, protein and structural influences. Critical among them are the biochemical, mechanical and architectural properties of the extracellular matrix (ECM). In recognition of the ECM's important role, cancer biologists have repurposed matrix mimetic culture systems first widely used by tissue engineers as new tools for in vitro study of tumor models. In this review we discuss the pathological changes in tumor ECM, the limitations of 2D culture on both traditional and polyacrylamide hydrogel surfaces in modeling these characteristics and advances in both naturally derived and synthetic scaffolds to facilitate more complex and controllable 3D cancer cell culture. Studies using naturally derived matrix materials like Matrigel and collagen have produced significant findings related to tumor morphogenesis and matrix invasion in a 3D environment and the mechanotransductive signaling that mediates key tumor-matrix interaction. However, lack of precise experimental control over important matrix factors in these matrices have increasingly led investigators to synthetic and semi-synthetic scaffolds that offer the engineering of specific ECM cues and the potential for more advanced experimental manipulations. Synthetic scaffolds composed of poly(ethylene glycol) (PEG), for example, facilitate highly biocompatible 3D culture, modular bioactive features like cell-mediated matrix degradation and complete independent control over matrix bioactivity and mechanics. Future work in PEG or similar reductionist synthetic matrix systems should enable the study of increasingly complex and dynamic tumor-ECM relationships in the hopes that accurate modeling of these relationships may reveal new cancer therapeutics targeting tumor progression and metastasis. © 2013 Elsevier Ltd.

Authors
Gill, BJ; West, JL
MLA Citation
Gill, BJ, and West, JL. "Modeling the tumor extracellular matrix: Tissue engineering tools repurposed towards new frontiers in cancer biology." Journal of Biomechanics 47.9 (June 27, 2014): 1969-1978.
Source
scopus
Published In
Journal of Biomechanics
Volume
47
Issue
9
Publish Date
2014
Start Page
1969
End Page
1978
DOI
10.1016/j.jbiomech.2013.09.029

Hydrogel-nanoparticle composites for optically modulated cancer therapeutic delivery.

A poly(N-isopropylacrylamide-co-acrylamide) (NIPAAm-co-AAm) hydrogel with near-infrared (NIR) absorbing silica-gold nanoshells was designed as a platform for pulsatile delivery of cancer therapeutics. This hydrogel was designed to have a lower critical solution temperature (LCST) above physiologic temperature, such that the material will transition from a hydrated state to a collapsed state above ~40°C. Additionally, the silica-gold nanoshells used were designed to have a peak extinction coefficient in the NIR, where penetration of light through tissue is maximal. This heat-triggered material phase transition of the composite was found to follow exposure of NIR light, indicating the ability of the NIR absorption by the nanoshells to sufficiently drive this transition. The composite material was loaded with either doxorubicin or a DNA duplex (a model nucleic acid therapeutic), two cancer therapeutics with differing physical and chemical properties. Release of both therapeutics was dramatically enhanced by NIR light exposure, causing 2-5x increase in drug release. Drug delivery profiles were influenced by both the molecular size of the drug as well as its chemical properties. The DNA therapeutic showed slower rates of nonspecific delivery by passive diffusion due to its larger size. Additionally, only 70% of the more hydrophobic doxorubicin was released from the material, whereas the more hydrophilic DNA showed over 90% release. Further, hydrogel composites were used to deliver the doxorubicin to CT.26-WT colon carcinoma cells, eliciting a therapeutic response. This work validates the potential application for this material in site-specific cancer therapeutic delivery.

Authors
Strong, LE; Dahotre, SN; West, JL
MLA Citation
Strong, LE, Dahotre, SN, and West, JL. "Hydrogel-nanoparticle composites for optically modulated cancer therapeutic delivery." Journal of controlled release : official journal of the Controlled Release Society 178 (March 2014): 63-68.
PMID
24462898
Source
epmc
Published In
Journal of Controlled Release
Volume
178
Publish Date
2014
Start Page
63
End Page
68
DOI
10.1016/j.jconrel.2014.01.014

Gadolinium-conjugated gold nanoshells for multimodal diagnostic imaging and photothermal cancer therapy

Multimodal imaging offers the potential to improve diagnosis and enhance the specificity of photothermal cancer therapy. Toward this goal, gadolinium-conjugated gold nanoshells are engineered and it is demonstrated that they enhance contrast for magnetic resonance imaging, X-ray, optical coherence tomography, reflectance confocal microscopy, and two-photon luminescence. Additionally, these particles effectively convert near-infrared light to heat, which can be used to ablate cancer cells. Ultimately, these studies demonstrate the potential of gadolinium-nanoshells for image-guided photothermal ablation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Authors
Coughlin, AJ; Ananta, JS; Deng, N; Larina, IV; Decuzzi, P; West, JL
MLA Citation
Coughlin, AJ, Ananta, JS, Deng, N, Larina, IV, Decuzzi, P, and West, JL. "Gadolinium-conjugated gold nanoshells for multimodal diagnostic imaging and photothermal cancer therapy." Small 10.3 (February 12, 2014): 556-565.
Source
scopus
Published In
Small
Volume
10
Issue
3
Publish Date
2014
Start Page
556
End Page
565
DOI
10.1002/smll.201302217

Mouse embryo manipulations with OCT guidance

Optical coherence tomography (OCT) is a three-dimensional, non-invasive optical imaging technique that relies on low-coherence interferometry. OCT has the capability of imaging 2 - 3 mm into tissue, which enables imaging of deeper structures within the embryo with a relatively high spatial resolution (2 - 15μm). Within the past decade, OCT has been increasingly used as a live imaging tool for embryonic cardiovascular research in several animal models. Research in our lab has recently shown that OCT can be used in combination with embryo culture for the visualization of early mammalian cardiovascular development (E7.5 - E10.0). Here, we demonstrate that OCT can be used for the guided microinjection of gold-silica nanoshell suspension into the cardiovascular system in live embryos without deleterious effect. This approach shows a promising application for the OCT guided delivery of contrast agents, viral vectors, therapeutic or pharmacological agents, signaling molecules or dyes to specific organ systems or tissues in live embryos and demonstrates a great potential for gold-silica nanoshells as a contrast agent in embryonic studies..

Authors
Garcia, MD; Syed, SH; Coughlin, AJ; Wang, S; West, JL; Larin, KV; Larina, IV
MLA Citation
Garcia, MD, Syed, SH, Coughlin, AJ, Wang, S, West, JL, Larin, KV, and Larina, IV. "Mouse embryo manipulations with OCT guidance." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 8953 (January 1, 2014).
Source
scopus
Published In
Proceedings of SPIE
Volume
8953
Publish Date
2014
DOI
10.1117/12.2045989

Fabrication of multifaceted, micropatterned surfaces and image-guided patterning using laser scanning lithography.

This protocol describes the implementation of laser scanning lithography (LSL) for the fabrication of multifaceted, patterned surfaces and for image-guided patterning. This photothermal-based patterning technique allows for selective removal of desired regions of an alkanethiol self-assembled monolayer on a metal film through raster scanning a focused 532 nm laser using a commercially available laser scanning confocal microscope. Unlike traditional photolithography methods, this technique does not require the use of a physical master and instead utilizes digital "virtual masks" that can be modified "on the fly" allowing for quick pattern modifications. The process to create multifaceted, micropatterned surfaces, surfaces that display pattern arrays of multiple biomolecules with each molecule confined to its own array, is described in detail. The generation of pattern configurations from user-chosen images, image-guided LSL is also described. This protocol outlines LSL in four basic sections. The first section details substrate preparation and includes cleaning of glass coverslips, metal deposition, and alkanethiol functionalization. The second section describes two ways to define pattern configurations, the first through manual input of pattern coordinates and dimensions using Zeiss AIM software and the second via image-guided pattern generation using a custom-written MATLAB script. The third section describes the details of the patterning procedure and postpatterning functionalization with an alkanethiol, protein, and both, and the fourth section covers cell seeding and culture. We end with a general discussion concerning the pitfalls of LSL and present potential improvements that can be made to the technique.

Authors
Slater, JH; West, JL
MLA Citation
Slater, JH, and West, JL. "Fabrication of multifaceted, micropatterned surfaces and image-guided patterning using laser scanning lithography." Methods in cell biology 119 (January 2014): 193-217.
PMID
24439286
Source
epmc
Published In
Methods in cell biology
Volume
119
Publish Date
2014
Start Page
193
End Page
217
DOI
10.1016/b978-0-12-416742-1.00011-1

Dual-energy micro-CT functional imaging of primary lung cancer in mice using gold and iodine nanoparticle contrast agents: a validation study.

To provide additional functional information for tumor characterization, we investigated the use of dual-energy computed tomography for imaging murine lung tumors. Tumor blood volume and vascular permeability were quantified using gold and iodine nanoparticles. This approach was compared with a single contrast agent/single-energy CT method. Ex vivo validation studies were performed to demonstrate the accuracy of in vivo contrast agent quantification by CT.Primary lung tumors were generated in LSL-Kras(G12D); p53(FL/FL) mice. Gold nanoparticles were injected, followed by iodine nanoparticles two days later. The gold accumulated in tumors, while the iodine provided intravascular contrast. Three dual-energy CT scans were performed-two for the single contrast agent method and one for the dual contrast agent method. Gold and iodine concentrations in each scan were calculated using a dual-energy decomposition. For each method, the tumor fractional blood volume was calculated based on iodine concentration, and tumor vascular permeability was estimated based on accumulated gold concentration. For validation, the CT-derived measurements were compared with histology and inductively-coupled plasma optical emission spectroscopy measurements of gold concentrations in tissues.Dual-energy CT enabled in vivo separation of gold and iodine contrast agents and showed uptake of gold nanoparticles in the spleen, liver, and tumors. The tumor fractional blood volume measurements determined from the two imaging methods were in agreement, and a high correlation (R(2) = 0.81) was found between measured fractional blood volume and histology-derived microvascular density. Vascular permeability measurements obtained from the two imaging methods agreed well with ex vivo measurements.Dual-energy CT using two types of nanoparticles is equivalent to the single nanoparticle method, but allows for measurement of fractional blood volume and permeability with a single scan. As confirmed by ex vivo methods, CT-derived nanoparticle concentrations are accurate. This method could play an important role in lung tumor characterization by CT.

Authors
Ashton, JR; Clark, DP; Moding, EJ; Ghaghada, K; Kirsch, DG; West, JL; Badea, CT
MLA Citation
Ashton, JR, Clark, DP, Moding, EJ, Ghaghada, K, Kirsch, DG, West, JL, and Badea, CT. "Dual-energy micro-CT functional imaging of primary lung cancer in mice using gold and iodine nanoparticle contrast agents: a validation study." PloS one 9.2 (January 2014): e88129-.
Website
http://hdl.handle.net/10161/11255
PMID
24520351
Source
epmc
Published In
PloS one
Volume
9
Issue
2
Publish Date
2014
Start Page
e88129
DOI
10.1371/journal.pone.0088129

Micropatterning of poly(ethylene glycol) diacrylate hydrogels.

This protocol describes the techniques to synthesize and fabricate micropatterned poly(ethylene glycol) diacrylate-based hydrogels that can be used as substrates in cellular studies and tissue engineering scaffolds. These materials provide an essentially bioinert background material due to the very low protein adsorption characteristics of poly(ethylene glycol), but the materials can be modified with covalently grafted peptides, proteins, or other biomolecules of interest to impart specific biofunctionality to the material. Further, it is possible to use micropatterning technologies to control the localization of such covalent grafting of biomolecules to the hydrogel materials, thus spatially controlling the cell-material interactions. This protocol presents a relatively simple approach for mask-based photolithographic patterning, generally best suited for patterning the surface of hydrogel materials for 2D cell studies. A more sophisticated technique, two-photon laser scanning lithography, is also presented. This technique allows free-form, 3D micropatterning in hydrogels.

Authors
Ali, S; Cuchiara, ML; West, JL
MLA Citation
Ali, S, Cuchiara, ML, and West, JL. "Micropatterning of poly(ethylene glycol) diacrylate hydrogels." Methods in cell biology 121 (January 2014): 105-119.
PMID
24560506
Source
epmc
Published In
Methods in cell biology
Volume
121
Publish Date
2014
Start Page
105
End Page
119
DOI
10.1016/b978-0-12-800281-0.00008-7

Covalent immobilization of stem cell factor and stromal derived factor 1α for in vitro culture of hematopoietic progenitor cells

Hematopoietic stem cells (HSCs) are currently utilized in the treatment of blood diseases, but widespread application of HSC therapeutics has been hindered by the limited availability of HSCs. With a better understanding of the HSC microenvironment and the ability to precisely recapitulate its components, we may be able to gain control of HSC behavior. In this work we developed a novel, biomimetic PEG hydrogel material as a substrate for this purpose and tested its potential with an anchorage-independent hematopoietic cell line, 32D clone 3 cells. We immobilized a fibronectin-derived adhesive peptide sequence, RGDS; a cytokine critical in HSC self-renewal, stem cell factor (SCF); and a chemokine important in HSC homing and lodging, stromal derived factor 1α (SDF1α), onto the surfaces of poly(ethylene glycol) (PEG) hydrogels. To evaluate the system's capabilities, we observed the effects of the biomolecules on 32D cell adhesion and morphology. We demonstrated that the incorporation of RGDS onto the surfaces promotes 32D cell adhesion in a dose-dependent fashion. We also observed an additive response in adhesion on surfaces with RGDS in combination with either SCF or SDF1α. In addition, the average cell area increased and circularity decreased on gel surfaces containing immobilized SCF or SDF1α, indicating enhanced cell spreading. By recapitulating aspects of the HSC microenvironment using a PEG hydrogel scaffold, we have shown the ability to control the adhesion and spreading of the 32D cells and demonstrated the potential of the system for the culture of primary hematopoietic cell populations. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Authors
Cuchiara, ML; Horter, KL; Banda, OA; West, JL
MLA Citation
Cuchiara, ML, Horter, KL, Banda, OA, and West, JL. "Covalent immobilization of stem cell factor and stromal derived factor 1α for in vitro culture of hematopoietic progenitor cells." Acta Biomaterialia 9.12 (December 1, 2013): 9258-9269.
Source
scopus
Published In
Acta Biomaterialia
Volume
9
Issue
12
Publish Date
2013
Start Page
9258
End Page
9269
DOI
10.1016/j.actbio.2013.08.012

Immobilization of Cell-Adhesive Laminin Peptides in Degradable PEGDA Hydrogels Influences Endothelial Cell Tubulogenesis.

Attachment, spreading, and organization of endothelial cells into tubule networks are mediated by interactions between cells in the extracellular microenvironment. Laminins are key extracellular matrix components and regulators of cell adhesion, migration, and proliferation. In this study, laminin-derived peptides were conjugated to poly(ethylene glycol) (PEG) monoacrylate and covalently incorporated into degradable PEG diacrylate (PEGDA) hydrogels to investigate the influence of these peptides on endothelial cellular adhesion and function in organizing into tubule networks. Degradable PEGDA hydrogels were synthesized by incorporating a matrix metalloproteinase (MMP)-sensitive peptide, GGGPQGIWGQGK (abbreviated PQ), into the polymer backbone. The secretion of MMP-2 and MMP-9 by endothelial cells promotes polymer degradation and consequently cell migration. We demonstrate the formation of extensive networks of tubule-like structures by encapsulated human umbilical vein endothelial cells in hydrogels with immobilized synthetic peptides. The resulting structures were stabilized by pericyte precursor cells (10T1/2s) in vitro. During tubule formation and stabilization, extracellular matrix proteins such as collagen IV and laminin were deposited. Tubules formed in the matrix of metalloproteinase sensitive hydrogels were visualized from 7 days to 4 weeks in response to different combination of peptides. Moreover, hydrogels functionalized with laminin peptides and transplanted in a mouse cornea supported the ingrowth and attachment of endothelial cells to the hydrogel during angiogenesis. Results of this study illustrate the use of laminin-derived peptides as potential candidates for modification of biomaterials to support angiogenesis.

Authors
Ali, S; Saik, JE; Gould, DJ; Dickinson, ME; West, JL
MLA Citation
Ali, S, Saik, JE, Gould, DJ, Dickinson, ME, and West, JL. "Immobilization of Cell-Adhesive Laminin Peptides in Degradable PEGDA Hydrogels Influences Endothelial Cell Tubulogenesis." Biores Open Access 2.4 (August 2013): 241-249.
PMID
23914330
Source
pubmed
Published In
BioResearch Open Access
Volume
2
Issue
4
Publish Date
2013
Start Page
241
End Page
249
DOI
10.1089/biores.2013.0021

Modeling the tumor extracellular matrix: Tissue engineering tools repurposed towards new frontiers in cancer biology

Authors
Gill, BJ; West, JL
MLA Citation
Gill, BJ, and West, JL. "Modeling the tumor extracellular matrix: Tissue engineering tools repurposed towards new frontiers in cancer biology." Journal of Biomechanics (2013).
PMID
24300038
Source
scopus
Published In
Journal of Biomechanics
Publish Date
2013

Three-dimensional photolithographic micropatterning: A novel tool to probe the complexities of cell migration

In order to independently study the numerous variables that influence cell movement, it will be necessary to employ novel tools and materials that allow for exquisite control of the cellular microenvironment. In this work, we have applied advanced 3D micropatterning technology, known as two-photon laser scanning lithography (TP-LSL), to poly(ethylene glycol) (PEG) hydrogels modified with bioactive peptides in order to fabricate precisely designed microenvironments to guide and quantitatively investigate cell migration. Specifically, TP-LSL was used to fabricate cell adhesive PEG-RGDS micropatterns on the surface of non-degradable PEG-based hydrogels (2D) and in the interior of proteolytically degradable PEG-based hydrogels (3D). HT1080 cell migration was guided down these adhesive micropatterns in both 2D and 3D, as observed via time-lapse microscopy. Differences in cell speed, cell persistence, and cell shape were observed based on variation of adhesive ligand, hydrogel composition, and patterned area for both 2D and 3D migration. Results indicated that HT1080s migrate faster and with lower persistence on 2D surfaces, while HT1080s migrating in 3D were smaller and more elongated. Further, cell migration was shown to have a biphasic dependence on PEG-RGDS concentration and cells moving within PEG-RGDS micropatterns were seen to move faster and with more persistence over time. Importantly, the work presented here begins to elucidate the multiple complex factors involved in cell migration, with typical confounding factors being independently controlled. The development of this unique platform will allow researchers to probe how cells behave within increasingly complex 3D microenvironments that begin to mimic specifically chosen aspects of the in vivo landscape. This journal is © The Royal Society of Chemistry.

Authors
Hoffmann, JC; West, JL
MLA Citation
Hoffmann, JC, and West, JL. "Three-dimensional photolithographic micropatterning: A novel tool to probe the complexities of cell migration." Integrative Biology (United Kingdom) 5.5 (2013): 817-827.
Source
scival
Published In
Integrative Biology
Volume
5
Issue
5
Publish Date
2013
Start Page
817
End Page
827
DOI
10.1039/c3ib20280a

Histogenesis in Three-Dimensional Scaffolds

Authors
McHale, MK; Bergmann, NM; West, JL
MLA Citation
McHale, MK, Bergmann, NM, and West, JL. "Histogenesis in Three-Dimensional Scaffolds." Handbook of Stem Cells 2 (2013): 951-963.
Source
scival
Published In
Handbook of Stem Cells
Volume
2
Publish Date
2013
Start Page
951
End Page
963
DOI
10.1016/B978-0-12-385942-6.00078-0

Multilayer micro fluidic poly(Ethylene Glycol) diacrylate hydrogels

Development of robust, in vivo like tissues in vitro holds the potential to create regenerative medicinebased therapeutics, provide more physiologically signi fi cant preclinical models and supply a pharmacological and toxicological screening platform that re fl ects in vivo systems in both complexity and function. This protocol describes a simple, robust, multilayer replica molding technique in which poly(dimethylsiloxane) (PDMS) and poly(ethylene glycol) diacrylate (PEGDA) are serially replica molded to develop micro fluidic PEGDA hydrogel networks embedded within independently fabricated PDMS housings, using a combination of soft and photo-lithography. This work has direct applications toward the development of robust, complex, cell-laden hydrogels for in vitro diagnostics and regenerative medicine applications © Springer Science+Business Media, LLC 2013.

Authors
Cuchiara, MP; West, JL
MLA Citation
Cuchiara, MP, and West, JL. "Multilayer micro fluidic poly(Ethylene Glycol) diacrylate hydrogels." Methods in Molecular Biology 949 (2013): 387-401.
Source
scival
Published In
Methods in molecular biology (Clifton, N.J.)
Volume
949
Publish Date
2013
Start Page
387
End Page
401
DOI
10.1007/978-1-62703-134-9-24

Three-dimensional photolithographic micropatterning: a novel tool to probe the complexities of cell migration

Authors
Hoffmann, JC; West, JL
MLA Citation
Hoffmann, JC, and West, JL. "Three-dimensional photolithographic micropatterning: a novel tool to probe the complexities of cell migration." INTEGRATIVE BIOLOGY 5.5 (2013): 817-827.
PMID
23460015
Source
wos-lite
Published In
Integrative Biology
Volume
5
Issue
5
Publish Date
2013
Start Page
817
End Page
827
DOI
10.1039/c3ib20280a

OCT guided microinjections for mouse embryonic research

Optical coherence tomography (OCT) is gaining popularity as live imaging tool for embryonic research in animal models. Recently we have demonstrated that OCT can be used for live imaging of cultured early mouse embryos (E7.5-E10) as well as later stage mouse embryos in utero (E12.5 to the end of gestation). Targeted delivery of signaling molecules, drugs, and cells is a powerful approach to study normal and abnormal development, and image guidance is highly important for such manipulations. Here we demonstrate that OCT can be used to guide microinjections of gold nanoshell suspensions in live mouse embryos. This approach can potentially be used for variety of applications such as guided injections of contrast agents, signaling molecules, pharmacological agents, cell transplantation and extraction, as well as other image-guided micromanipulations. Our studies also reveal novel potential for gold nanoshells in embryonic research. © 2013 Copyright SPIE.

Authors
Larin, KV; Syed, SH; Coughlin, AJ; Wang, S; West, JL; Dickinson, ME; Larina, IV
MLA Citation
Larin, KV, Syed, SH, Coughlin, AJ, Wang, S, West, JL, Dickinson, ME, and Larina, IV. "OCT guided microinjections for mouse embryonic research." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 8593 (2013).
Source
scival
Published In
Proceedings of SPIE
Volume
8593
Publish Date
2013
DOI
10.1117/12.2006213

Fibulin-2 Is a Driver of Malignant Progression in Lung Adenocarcinoma

The extracellular matrix of epithelial tumors undergoes structural remodeling during periods of uncontrolled growth, creating regional heterogeneity and torsional stress. How matrix integrity is maintained in the face of dynamic biophysical forces is largely undefined. Here we investigated the role of fibulin-2, a matrix glycoprotein that functions biomechanically as an inter-molecular clasp and thereby facilitates supra-molecular assembly. Fibulin-2 was abundant in the extracellular matrix of human lung adenocarcinomas and was highly expressed in tumor cell lines derived from mice that develop metastatic lung adenocarcinoma from co-expression of mutant K-ras and p53. Loss-of-function experiments in tumor cells revealed that fibulin-2 was required for tumor cells to grow and metastasize in syngeneic mice, a surprising finding given that other intra-tumoral cell types are known to secrete fibulin-2. However, tumor cells grew and metastasized equally well in Fbln2-null and -wild-type littermates, implying that malignant progression was dependent specifically upon tumor cell-derived fibulin-2, which could not be offset by other cellular sources of fibulin-2. Fibulin-2 deficiency impaired the ability of tumor cells to migrate and invade in Boyden chambers, to create a stiff extracellular matrix in mice, to cross-link secreted collagen, and to adhere to collagen. We conclude that fibulin-2 is a driver of malignant progression in lung adenocarcinoma and plays an unexpected role in collagen cross-linking and tumor cell adherence to collagen. © 2013 Baird et al.

Authors
Baird, BN; Schliekelman, MJ; Ahn, Y-H; Chen, Y; Roybal, JD; Gill, BJ; Mishra, DK; Erez, B; O'Reilly, M; Yang, Y; Patel, M; Liu, X; Thilaganathan, N; Larina, IV; Dickinson, ME; West, JL; Gibbons, DL; Liu, DD; Kim, MP; Hicks, JM; Wistuba, II; Hanash, SM; Kurie, JM
MLA Citation
Baird, BN, Schliekelman, MJ, Ahn, Y-H, Chen, Y, Roybal, JD, Gill, BJ, Mishra, DK, Erez, B, O'Reilly, M, Yang, Y, Patel, M, Liu, X, Thilaganathan, N, Larina, IV, Dickinson, ME, West, JL, Gibbons, DL, Liu, DD, Kim, MP, Hicks, JM, Wistuba, II, Hanash, SM, and Kurie, JM. "Fibulin-2 Is a Driver of Malignant Progression in Lung Adenocarcinoma." PLoS ONE 8.6 (2013).
PMID
23785517
Source
scival
Published In
PloS one
Volume
8
Issue
6
Publish Date
2013
DOI
10.1371/journal.pone.0067054

Fabrication and mechanical evaluation of anatomically-inspired quasilaminate hydrogel structures with layer-specific formulations

A major tissue engineering challenge is the creation of multilaminate scaffolds with layer-specific mechanical properties representative of native tissues, such as heart valve leaflets, blood vessels, and cartilage. For this purpose, poly(ethylene glycol) diacrylate (PEGDA) hydrogels are attractive materials due to their tunable mechanical and biological properties. This study explored the fabrication of trilayer hydrogel quasilaminates. A novel sandwich method was devised to create quasilaminates with layers of varying stiffnesses. The trilayer structure was comprised of two "stiff" outer layers and one "soft" inner layer. Tensile testing of bilayer quasilaminates demonstrated that these scaffolds do not fail at the interface. Flexural testing showed that the bending modulus of acellular quasilaminates fell between the bending moduli of the "stiff" and "soft" hydrogel layers. The bending modulus and swelling of trilayer scaffolds with the same formulations were not significantly different than single layer gels of the same formulation. The encapsulation of cells and the addition of phenol red within the hydrogel layers decreased bending modulus of the trilayer scaffolds. The data presented demonstrates that this fabrication method can make quasilaminates with robust interfaces, integrating layers of different mechanical properties and biofunctionalization, and thus forming the foundation for a multilaminate scaffold that more accurately represents native tissue. © 2012 Biomedical Engineering Society.

Authors
Tseng, H; Cuchiara, ML; Durst, CA; Cuchiara, MP; Lin, CJ; West, JL; Grande-Allen, KJ
MLA Citation
Tseng, H, Cuchiara, ML, Durst, CA, Cuchiara, MP, Lin, CJ, West, JL, and Grande-Allen, KJ. "Fabrication and mechanical evaluation of anatomically-inspired quasilaminate hydrogel structures with layer-specific formulations." Annals of Biomedical Engineering 41.2 (2013): 398-407.
Source
scival
Published In
Annals of Biomedical Engineering
Volume
41
Issue
2
Publish Date
2013
Start Page
398
End Page
407
DOI
10.1007/s10439-012-0666-5

Nitric oxide-releasing polymeric microspheres improve diabetes-related erectile dysfunction

Introduction: We have used a long-acting nitric oxide (NO)-releasing polymer to develop injectable biodegradable microspheres capable of localized NO release over prolonged periods of time. Aim: The aim of this study was to evaluate the therapeutic potential of these microspheres for diabetes-related erectile dysfunction (ED) in the rat model. Methods: NO-releasing microspheres were incubated in physiologic buffer, and in vitroNO release was measured using a Griess assay. To ensure no migration, microspheres were fluorescently tagged and injected into the corpus cavernosum of adult rats, and fluorescent imaging was performed weekly for 4 weeks, at which point rats were sacrificed. To assess physiologic efficacy, diabetes was induced in 40 rats using streptozotocin (STZ), whereas 10 rats were kept as age-matched controls. Diabetic rats were divided into four groups: no treatment, sildenafil, NO-releasing microspheres, and combination therapy. For each rat, the cavernosal nerve (CN) was stimulated at various voltages, and intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured via corpus cavernosum and carotid artery catheterization, respectively. Long-term efficacy was determined by injecting diabetic rats with microspheres and measuring erectile response at predetermined intervals for up to 5 weeks. Main Outcome Measures: Erectile response was determined via calculation of mean peak ICP/MAP and area under curve (AUC) for each experimental group. Results: Under physiologic conditions in vitro, microspheres continued NO release for up to 4 weeks. Fluorescent imaging revealed no detectable signal in tissues besides cavernosal tissue at 4 weeks postinjection. Upon CN stimulation, peak ICP/MAP ratio and AUC of diabetic rats improved significantly (P<0.05) in microsphere and combination therapy groups compared with no treatment and sildenafil groups. In long-term efficacy studies, microspheres augmented the effect of sildenafil for 3 weeks following injection (P<0.05). Conclusions: NO-releasing microspheres significantly improved erectile response in diabetic rats for 3 weeks and hence offer a promising approach to ED therapy, either as monotherapy or combination therapy. © 2013 International Society for Sexual Medicine.

Authors
Soni, SD; Song, W; West, JL; Khera, M
MLA Citation
Soni, SD, Song, W, West, JL, and Khera, M. "Nitric oxide-releasing polymeric microspheres improve diabetes-related erectile dysfunction." Journal of Sexual Medicine 10.8 (2013): 1915-1925.
PMID
23751157
Source
scival
Published In
The Journal of Sexual Medicine
Volume
10
Issue
8
Publish Date
2013
Start Page
1915
End Page
1925
DOI
10.1111/jsm.12216

Rapid healing of femoral defects in rats with low dose sustained BMP2 expression from PEGDA hydrogel microspheres

Current strategies for bone regeneration after traumatic injury often fail to provide adequate healing and integration. Here, we combined the poly (ethylene glycol) diacrylate (PEGDA) hydrogel with allogeneic "carrier" cells transduced with an adenovirus expressing BMP2. The system is unique in that the biomaterial encapsulates the cells, shielding them and thus suppressing destructive inflammatory processes. Using this system, complete healing of a 5 mm-long femur defect in a rat model occurs in under 3 weeks, through secretion of 100-fold lower levels of protein as compared to doses of recombinant BMP2 protein used in studies which lead to healing in 2-3 months. New bone formation was evaluated radiographically, histologically, and biomechanically at 2, 3, 6, 9, and 12 weeks after surgery. Rapid bone formation bridged the defect area and reliably integrated into the adjacent skeletal bone as early as 2 weeks. At 3 weeks, biomechanical analysis showed the new bone to possess 79% of torsional strength of the intact contralateral femur. Histological evaluation showed normal bone healing, with no infiltration of inflammatory cells with the bone being stable approximately 1 year later. We propose that these osteoinductive microspheres offer a more efficacious and safer clinical option over the use of rhBMP2. Copyright © 2013 Orthopaedic Research Society.

Authors
Sonnet, C; Simpson, CL; Olabisi, RM; Sullivan, K; Lazard, Z; Gugala, Z; Peroni, JF; Weh, JM; Davis, AR; West, JL; Olmsted-Davis, EA
MLA Citation
Sonnet, C, Simpson, CL, Olabisi, RM, Sullivan, K, Lazard, Z, Gugala, Z, Peroni, JF, Weh, JM, Davis, AR, West, JL, and Olmsted-Davis, EA. "Rapid healing of femoral defects in rats with low dose sustained BMP2 expression from PEGDA hydrogel microspheres." Journal of Orthopaedic Research 31.10 (2013): 1597-1604.
PMID
23832813
Source
scival
Published In
Journal of Orthopaedic Research
Volume
31
Issue
10
Publish Date
2013
Start Page
1597
End Page
1604
DOI
10.1002/jor.22407

Multilayer microfluidic poly(ethylene glycol) diacrylate hydrogels.

Development of robust, in vivo like tissues in vitro holds the potential to create regenerative medicine-based therapeutics, provide more physiologically significant preclinical models and supply a pharmacological and toxicological screening platform that reflects in vivo systems in both complexity and function. This protocol describes a simple, robust, multilayer replica molding technique in which poly(dimethylsiloxane) (PDMS) and poly(ethylene glycol) diacrylate (PEGDA) are serially replica molded to develop microfluidic PEGDA hydrogel networks embedded within independently fabricated PDMS housings, using a combination of soft and photo-lithography. This work has direct applications toward the development of robust, complex, cell-laden hydrogels for in vitro diagnostics and regenerative medicine applications.

Authors
Cuchiara, MP; West, JL
MLA Citation
Cuchiara, MP, and West, JL. "Multilayer microfluidic poly(ethylene glycol) diacrylate hydrogels." Methods in molecular biology (Clifton, N.J.) 949 (2013): 387-401.
PMID
23329455
Source
scival
Published In
Methods in molecular biology (Clifton, N.J.)
Volume
949
Publish Date
2013
Start Page
387
End Page
401
DOI
10.1007/978-1-62703-134-9_24

Covalent immobilization of stem cell factor and stromal derived factor 1α for in vitro culture of hematopoietic progenitor cells

Hematopoietic stem cells (HSCs) are currently utilized in the treatment of blood diseases, but widespread application of HSC therapeutics has been hindered by the limited availability of HSCs. With a better understanding of the HSC microenvironment and the ability to precisely recapitulate its components, we may be able to gain control of HSC behavior. In this work we developed a novel, biomimetic PEG hydrogel material as a substrate for this purpose and tested its potential with an anchorage-independent hematopoietic cell line, 32D clone 3 cells. We immobilized a fibronectin-derived adhesive peptide sequence, RGDS; a cytokine critical in HSC self-renewal, stem cell factor (SCF); and a chemokine important in HSC homing and lodging, stromal derived factor 1α (SDF1α), onto the surfaces of poly(ethylene glycol) (PEG) hydrogels. To evaluate the system's capabilities, we observed the effects of the biomolecules on 32D cell adhesion and morphology. We demonstrated that the incorporation of RGDS onto the surfaces promotes 32D cell adhesion in a dose-dependent fashion. We also observed an additive response in adhesion on surfaces with RGDS in combination with either SCF or SDF1α. In addition, the average cell area increased and circularity decreased on gel surfaces containing immobilized SCF or SDF1α, indicating enhanced cell spreading. By recapitulating aspects of the HSC microenvironment using a PEG hydrogel scaffold, we have shown the ability to control the adhesion and spreading of the 32D cells and demonstrated the potential of the system for the culture of primary hematopoietic cell populations. © 2013 Acta Materialia Inc.

Authors
Cuchiara, ML; Horter, KL; Banda, OA; West, JL
MLA Citation
Cuchiara, ML, Horter, KL, Banda, OA, and West, JL. "Covalent immobilization of stem cell factor and stromal derived factor 1α for in vitro culture of hematopoietic progenitor cells." Acta Biomaterialia (2013).
PMID
23958779
Source
scival
Published In
Acta Biomaterialia
Publish Date
2013
DOI
10.1016/j.actbio.2013.08.012

Gadolinium-Conjugated Gold Nanoshells for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy

Authors
Coughlin, AJ; Ananta, JS; Deng, N; Larina, IV; Decuzzi, P; West, JL
MLA Citation
Coughlin, AJ, Ananta, JS, Deng, N, Larina, IV, Decuzzi, P, and West, JL. "Gadolinium-Conjugated Gold Nanoshells for Multimodal Diagnostic Imaging and Photothermal Cancer Therapy." Small (2013).
PMID
24115690
Source
scopus
Published In
Small
Publish Date
2013

Targeting gold nanoparticles for cancer diagnostics and therapeutics

Gold nanoparticles are particularly appealing for cancer medicine because of their plasmonic optical properties that can be exploited for both diagnostic and therapeutic purposes, along with their established biocompatibility and ease of surface modification. Additionally, a variety of targeting moieties has been incorporated on gold nanostructures to achieve high cancer cell specificity and potentially enhanced tumor uptake in vivo. Here we describe the synthesis of four gold nanoparticle types: gold colloid, gold-silica nanoshells, gold-gold sulfide nanoparticles, and gold nanorods. Each of these four particles has demonstrated success in both optical imaging and photothermal ablation of cancer. Methods by which each particle can be conjugated to targeting proteins, characterized for their degree of protein conjugation, and then evaluated for their potential to bind cell surface markers overexpressed on tumor cells is also discussed. Copyright © 2012 American Chemical Society.

Authors
Coughlin, AJ; West, JL
MLA Citation
Coughlin, AJ, and West, JL. "Targeting gold nanoparticles for cancer diagnostics and therapeutics." ACS Symposium Series 1113 (November 26, 2012): 37-54.
Source
scopus
Published In
ACS Symposium Series
Volume
1113
Publish Date
2012
Start Page
37
End Page
54
DOI
10.1021/bk-2012-1113.ch003

Gold nanoshells for imaging and photothermal ablation of cancer

Gold nanoshells consist of a thin, gold shell over a non-conductive core material, such as silica or gold-sulfide. Designed to scatter and absorb light within the near-infrared (NIR) water window, these particles can be employed for both optical imaging and photothermal ablation of cancer. This chapter provides a brief overview of nanotechnology's role in cancer medicine followed by an in-depth discussion of gold nanoshells, their optical properties and use thus far as a cancer diagnostic and therapeutic tool in vitro and in vivo. © 2012 Woodhead Publishing Limited All rights reserved.

Authors
Coughlin, AJ; West, JL
MLA Citation
Coughlin, AJ, and West, JL. "Gold nanoshells for imaging and photothermal ablation of cancer." (October 1, 2012): 326-355. (Chapter)
Source
scopus
Publish Date
2012
Start Page
326
End Page
355
DOI
10.1533/9780857096449.2.326

Integration of self-assembled microvascular networks with microfabricated PEG-based hydrogels

Despite tremendous efforts, tissue engineered constructs are restricted to thin, simple tissues sustained only by diffusion. The most significant barrier in tissue engineering is insufficient vascularization to deliver nutrients and metabolites during development in vitro and to facilitate rapid vascular integration in vivo. Tissue engineered constructs can be greatly improved by developing perfusable microvascular networks in vitro in order to provide transport that mimics native vascular organization and function. Here a microfluidic hydrogel is integrated with a self-assembling pro-vasculogenic co-culture in a strategy to perfuse microvascular networks in vitro. This approach allows for control over microvascular network self-assembly and employs an anastomotic interface for integration of self-assembled microvascular networks with fabricated microchannels. As a result, transport within the system shifts from simple diffusion to vessel supported convective transport and extra-vessel diffusion, thus improving overall mass transport properties. This work impacts the development of perfusable prevascularized tissues in vitro and ultimately tissue engineering applications in vivo. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Authors
Cuchiara, MP; Gould, DJ; McHale, MK; Dickinson, ME; West, JL
MLA Citation
Cuchiara, MP, Gould, DJ, McHale, MK, Dickinson, ME, and West, JL. "Integration of self-assembled microvascular networks with microfabricated PEG-based hydrogels." Advanced Functional Materials 22.21 (2012): 4511-4518.
Source
scival
Published In
Advanced Functional Materials
Volume
22
Issue
21
Publish Date
2012
Start Page
4511
End Page
4518
DOI
10.1002/adfm.201200976

A synthetic matrix with independently tunable biochemistry and mechanical properties to study epithelial morphogenesis and EMT in a lung adenocarcinoma model

Better understanding of the biophysical and biochemical cues of the tumor extracellular matrix environment that influence metastasis may have important implications for new cancer therapeutics. Initial exploration into this question has used naturally derived protein matrices that suffer from variability, poor control over matrix biochemistry, and inability to modify the matrix biochemistry and mechanics. Here, we report the use of a synthetic polymer-based scaffold composed primarily of poly(ethylene glycol), or PEG, modified with bioactive peptides to study murine models of lung adenocarcinoma. In this study, we focus on matrix-derived influences on epithelial morphogenesis of a metastatic cell line (344SQ) that harbors mutations in Kras and p53 (trp53) and is prone to a microRNA-200 (miR-200)-dependent epithelial-mesenchymal transition (EMT) and metastasis. The modified PEG hydrogels feature biospecific cell adhesion and cell-mediated proteolytic degradation with independently adjustable matrix stiffness. 344SQ encapsulated in bioactive peptide-modified, matrix metalloproteinase- degradable PEG hydrogels formed lumenized epithelial spheres comparable to that seen with three-dimensional culture in Matrigel. Altering both matrix stiffness and the concentration of cell-adhesive ligand signi ficantly influenced epithelial morphogenesis as manifest by differences in the extent of lumenization, in patterns of intrasphere apoptosis and proliferation, and in expression of epithelial polarity markers. Regardless of matrix composition, exposure to TGF-β induced a loss of epithelial morphologic features, shift in expression of EMT marker genes, and decrease in mir-200 levels consistent with EMT. Our findings help illuminate matrixderived cues that influence epithelial morphogenesis and highlight the potential utility that this synthetic matrixmimetic tool has for cancer biology. ©2012 AACR.

Authors
Gill, BJ; Gibbons, DL; Roudsari, LC; Saik, JE; Rizvi, ZH; Roybal, JD; Kurie, JM; West, JL
MLA Citation
Gill, BJ, Gibbons, DL, Roudsari, LC, Saik, JE, Rizvi, ZH, Roybal, JD, Kurie, JM, and West, JL. "A synthetic matrix with independently tunable biochemistry and mechanical properties to study epithelial morphogenesis and EMT in a lung adenocarcinoma model." Cancer Research 72.22 (2012): 6013-6023.
PMID
22952217
Source
scival
Published In
Cancer Research
Volume
72
Issue
22
Publish Date
2012
Start Page
6013
End Page
6023
DOI
10.1158/0008-5472.CAN-12-0895

Vascular-targeted photothermal therapy of an orthotopic murine glioma model

Aim: To develop nanoshells for vascular-targeted photothermal therapy of glioma. Materials & methods: The ability of nanoshells conjugated to VEGF and/or poly(ethylene glycol) (PEG) to thermally ablate VEGF receptor-2-positive endothelial cells upon near-infrared laser irradiation was evaluated in vitro. Subsequent in vivo studies evaluated therapy in mice bearing intracerebral glioma tumors by exposing tumors to near-infrared light after systemically delivering saline, PEG-coated nanoshells, or VEGF-coated nanoshells. The treatment effect was monitored with intravital microscopy and histology. Results: VEGF-coated but not PEG-coated nanoshells bound VEGF receptor-2-positive cells in vitro to enable targeted photothermal ablation. In vivo, VEGF targeting doubled the proportion of nanoshells bound to tumor vessels and vasculature was disrupted following laser exposure. Vessels were not disrupted in mice that received saline. The normal brain was unharmed in all treatment and control mice. Conclusion: Nanoshell therapy can induce vascular disruption in glioma. © 2012 Future Medicine Ltd.

Authors
Day, ES; Zhang, L; Thompson, PA; Zawaski, JA; Kaffes, CC; Gaber, MW; Blaney, SM; West, JL
MLA Citation
Day, ES, Zhang, L, Thompson, PA, Zawaski, JA, Kaffes, CC, Gaber, MW, Blaney, SM, and West, JL. "Vascular-targeted photothermal therapy of an orthotopic murine glioma model." Nanomedicine 7.8 (2012): 1133-1148.
PMID
22583571
Source
scival
Published In
Nanomedicine (London, England)
Volume
7
Issue
8
Publish Date
2012
Start Page
1133
End Page
1148
DOI
10.2217/nnm.11.189

Three-dimensional biomimetic patterning in hydrogels to guide cellular organization

An image-guided micropatterning method is demonstrated for generating biomimetic hydrogel scaffolds with two-photon laser scanning photolithography. This process utilizes computational methods to directly translate three-dimensional cytoarchitectural features from labeled tissues into material structures. We use this method to pattern hydrogels that guide cellular organization by structurally and biochemically recapitulating complex vascular niche microenvironments with high pattern fidelity at the microscale. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Authors
Culver, JC; Hoffmann, JC; Poché, RA; Slater, JH; West, JL; Dickinson, ME
MLA Citation
Culver, JC, Hoffmann, JC, Poché, RA, Slater, JH, West, JL, and Dickinson, ME. "Three-dimensional biomimetic patterning in hydrogels to guide cellular organization." Advanced Materials 24.17 (2012): 2344-2348.
PMID
22467256
Source
scival
Published In
Advanced Materials
Volume
24
Issue
17
Publish Date
2012
Start Page
2344
End Page
2348
DOI
10.1002/adma.201200395

Biofunctional materials for directing vascular development

Engineered tissue constructs are inherently limited by their lack of microvascularization. Evidence suggests that combining a scaffold material with cells and their cell-secreted signals instigates tubule formation, and various strategies can be employed to tailor the vascular response. This review focuses on rationally designed materials capable of supporting functional neovessel formation and stabilization. Biomaterial scaffolds and their use as growth factor delivery systems are discussed, as well as other functional enhancement strategies to direct cellular responses for effective formation of a mature vascular network. © 2012 Bentham Science Publishers.

Authors
Saik, JE; McHale, MK; West, JL
MLA Citation
Saik, JE, McHale, MK, and West, JL. "Biofunctional materials for directing vascular development." Current Vascular Pharmacology 10.3 (2012): 331-341.
PMID
22239635
Source
scival
Published In
Current vascular pharmacology
Volume
10
Issue
3
Publish Date
2012
Start Page
331
End Page
341
DOI
10.2174/157016112799959314

Fabrication and Mechanical Evaluation of Anatomically-Inspired Quasilaminate Hydrogel Structures with Layer-Specific Formulations

A major tissue engineering challenge is the creation of multilaminate scaffolds with layer-specific mechanical properties representative of native tissues, such as heart valve leaflets, blood vessels, and cartilage. For this purpose, poly(ethylene glycol) diacrylate (PEGDA) hydrogels are attractive materials due to their tunable mechanical and biological properties. This study explored the fabrication of trilayer hydrogel quasilaminates. A novel sandwich method was devised to create quasilaminates with layers of varying stiffnesses. The trilayer structure was comprised of two "stiff" outer layers and one "soft" inner layer. Tensile testing of bilayer quasilaminates demonstrated that these scaffolds do not fail at the interface. Flexural testing showed that the bending modulus of acellular quasilaminates fell between the bending moduli of the "stiff" and "soft" hydrogel layers. The bending modulus and swelling of trilayer scaffolds with the same formulations were not significantly different than single layer gels of the same formulation. The encapsulation of cells and the addition of phenol red within the hydrogel layers decreased bending modulus of the trilayer scaffolds. The data presented demonstrates that this fabrication method can make quasilaminates with robust interfaces, integrating layers of different mechanical properties and biofunctionalization, and thus forming the foundation for a multilaminate scaffold that more accurately represents native tissue. © 2012 Biomedical Engineering Society.

Authors
Tseng, H; Cuchiara, ML; Durst, CA; Cuchiara, MP; Lin, CJ; West, JL; Grande-Allen, KJ
MLA Citation
Tseng, H, Cuchiara, ML, Durst, CA, Cuchiara, MP, Lin, CJ, West, JL, and Grande-Allen, KJ. "Fabrication and Mechanical Evaluation of Anatomically-Inspired Quasilaminate Hydrogel Structures with Layer-Specific Formulations." Annals of Biomedical Engineering (2012): 1-10.
PMID
23053300
Source
scival
Published In
Annals of Biomedical Engineering
Publish Date
2012
Start Page
1
End Page
10
DOI
10.1007/s10439-012-0666-5

Rapid heterotrophic ossification with cryopreserved poly(ethylene glycol-) microencapsulated BMP2-expressing MSCs

Autologous bone grafting is the most effective treatment for long-bone nonunions, but it poses considerable risks to donors, necessitating the development of alternative therapeutics. Poly(ethylene glycol) (PEG) microencapsulation and BMP2 transgene delivery are being developed together to induce rapid bone formation. However, methods to make these treatments available for clinical applications are presently lacking. In this study we used mesenchymal stem cells (MSCs) due to their ease of harvest, replication potential, and immunomodulatory capabilities. MSCs were from sheep and pig due to their appeal as large animal models for bone nonunion. We demonstrated that cryopreservation of these microencapsulated MSCs did not affect their cell viability, adenoviral BMP2 production, or ability to initiate bone formation. Additionally, microspheres showed no appreciable damage from cryopreservation when examined with light and electron microscopy. These results validate the use of cryopreservation in preserving the viability and functionality of PEG-encapsulated BMP2-transduced MSCs. © 2012 Jennifer Mumaw et al.

Authors
Mumaw, J; Jordan, ET; Sonnet, C; Olabisi, RM; Olmsted-Davis, EA; Davis, AR; Peroni, JF; West, JL; West, F; Lu, Y; Stice, SL
MLA Citation
Mumaw, J, Jordan, ET, Sonnet, C, Olabisi, RM, Olmsted-Davis, EA, Davis, AR, Peroni, JF, West, JL, West, F, Lu, Y, and Stice, SL. "Rapid heterotrophic ossification with cryopreserved poly(ethylene glycol-) microencapsulated BMP2-expressing MSCs." International Journal of Biomaterials (2012).
Source
scival
Published In
International Journal of Biomaterials
Publish Date
2012
DOI
10.1155/2012/861794

Visible light photoinitiation of mesenchymal stem cell-laden bioresponsive hydrogels

Biological activity can be added to synthetic scaffolds by incorporating functional peptide sequences that provide enzyme-mediated degradation sites, facilitate cellular adhesion or stimulate signaling pathways. Poly(ethylene glycol) diacrylate is a popular synthetic base for tissue engineering scaffolds because it creates a hydrophilic environment that can be chemically manipulated to add this biological functionality. Furthermore, the acrylate groups allow for encapsulation of cells using photopolymerization under physiological conditions. One complication with the addition of these peptides is that aromatic amino acids absorb light at 285nm and compete with the ultraviolet (UV)-sensitive photoinitiators such as IrgacureTM 2959 (I2959), the most commonly used initiator for cytocompatible photoencapsulation of cells into synthetic scaffolds. In this study we define non-toxic conditions for photoencapsulation of human mesenchymal stem cells (hMSC) in PEGDA scaffolds using a visible light photoinitiator system composed of eosin Y, triethanolamine and 1-vinyl-2-pyrrolidinone. This visible light photoinitiator produced hydrogel scaffolds with an increased viability of encapsulated hMSCs and a more tightly crosslinked network in one-third the time of UV polymerization with I2959.

Authors
Bahney, CS; Lujan, TJ; Hsu, CW; Bottlang, M; West, JL; Johnstone, B
MLA Citation
Bahney, CS, Lujan, TJ, Hsu, CW, Bottlang, M, West, JL, and Johnstone, B. "Visible light photoinitiation of mesenchymal stem cell-laden bioresponsive hydrogels." European Cells and Materials 22 (2011): 43-55.
PMID
21761391
Source
scival
Published In
European cells & materials
Volume
22
Publish Date
2011
Start Page
43
End Page
55

Mitral valvular interstitial cell responses to substrate stiffness depend on age and anatomic region

The material properties of heart valves depend on the subject's age, the state of the disease and the complex valvular microarchitecture. Furthermore, valvular interstitial cells (VICs) are mechanosensitive, and their synthesis of extracellular matrix not only determines the valve's material properties but also provides an adhesive substrate for VICs. However, the interrelationship between substrate stiffness and VIC phenotype and synthetic properties is poorly understood. Given that the local mechanical environment (substrate stiffness) surrounding VICs differs among different age groups and different anatomic regions of the valve, it was hypothesized that there may be an age- and valve-region-specific response of VICs to substrate stiffness. Therefore, 6-week-, 6-month- and 6-year-old porcine VICs from the center of the mitral valve anterior leaflet (MVAC) and posterior leaflet (PML) were seeded onto poly(ethylene) glycol hydrogels of different stiffnesses and stained for markers of VIC activation (smooth muscle alpha-actin (SMaA)) and collagen synthesis (heat shock protein-47 (HSP47), prolyl 4-hydroxylase (P4H)). Six-week-old MVAC demonstrated decreased SMaA, P4H and HSP47 on stiffer gels, while 6-week-old PML only demonstrated decreased HSP47. Six-month-old MVAC demonstrated no difference between substrates, while 6-month-old PML demonstrated decreased SMaA, P4H and HSP47. Six-year-old MVAC demonstrated decreased P4H and HSP47, while 6-year-old PML demonstrated decreased P4H and increased HSP47. In conclusion, the age-specific and valve-region-specific responses of VICs to substrate stiffness link VIC phenotype to the leaflet regional matrix in which the VICs reside. These data provide further rationale for investigating the role of substrate stiffness in VIC remodeling within diseased and tissue engineered valves. © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Authors
Stephens, EH; Durst, CA; West, JL; Grande-Allen, KJ
MLA Citation
Stephens, EH, Durst, CA, West, JL, and Grande-Allen, KJ. "Mitral valvular interstitial cell responses to substrate stiffness depend on age and anatomic region." Acta Biomaterialia 7.1 (2011): 75-82.
PMID
20624493
Source
scival
Published In
Acta Biomaterialia
Volume
7
Issue
1
Publish Date
2011
Start Page
75
End Page
82
DOI
10.1016/j.actbio.2010.07.001

Micron-scale spatially patterned, covalently immobilized vascular endothelial growth factor on hydrogels accelerates endothelial tubulogenesis and increases cellular angiogenic responses

Spontaneous formation of endothelial tubules was restricted to patterned micron-scale regions presenting cell adhesion ligands and angiogenic signaling protein on poly(ethylene glycol) hydrogels. Arginine-glycine-aspartic acid-serine (RGDS), an integrin ligand, and vascular endothelial growth factor (VEGF), a rate-limiting signaling protein involved in angiogenesis, were covalently bound through photopolymerization via laser scanning lithography to the surface of poly(ethylene glycol) hydrogels in patterned micron-scale regions. Endothelial cells cultured in this restricted environment underwent accelerated tubulogenesis, forming endothelial tubes within 2 days, whereas cells cultured on larger patterned areas remained spread and did not form tubules by day 2. Tubules formed in 2 days on RGDS and VEGF patterns were observed to possess lumens; however, tubule-like structures formed in 2 days on RGDS-only control patterns did not have observable lumens. Additionally, tubules that formed on restricted areas of RGDS and VEGF expressed more VEGF receptor 1, VEGF receptor 2, and ephA7 surface markers, in addition to higher expression of laminin, than cells remaining spread on wide patterned lines. This work reports spatial control and acceleration of endothelial tubule formation using biocompatible hydrogel materials to allow the formation of highly organized vascularized tissues. © 2011 Mary Ann Liebert, Inc.

Authors
Leslie-Barbick, JE; Shen, C; Chen, C; West, JL
MLA Citation
Leslie-Barbick, JE, Shen, C, Chen, C, and West, JL. "Micron-scale spatially patterned, covalently immobilized vascular endothelial growth factor on hydrogels accelerates endothelial tubulogenesis and increases cellular angiogenic responses." Tissue Engineering - Part A 17.1-2 (2011): 221-229.
PMID
20712418
Source
scival
Published In
Tissue Engineering, Part A
Volume
17
Issue
1-2
Publish Date
2011
Start Page
221
End Page
229
DOI
10.1089/ten.tea.2010.0202

Flexural characterization of cell encapsulated PEGDA hydrogels with applications for tissue engineered heart valves

The limitations of the current clinical options for valve replacements have inspired the development of enabling technologies to create a tissue engineered heart valve (TEHV). Poly(ethylene glycol) diacrylate (PEGDA) hydrogel scaffolds permit greater biological and biomechanical customization than do non-woven mesh scaffold technologies. However, the material characterization of PEGDA hydrogels has been predominantly limited to compression and tension, as opposed to bending. Since large flexural deformations result in points of maximum stress in native valves as well as TEHVs, it is crucial to evaluate any potential scaffold material in this mode. The effect of formulation parameters on the bending mechanics of cell-seeded PEGDA hydrogels were investigated with a custom designed bending tester. Three molecular weights (3.4, 6, and 8 kDa) and three weight fractions (5%, 10%, and 15%, w/v) were subjected to three-point bending tests and the flexural stiffness was calculated. Manipulating the composition of the hydrogels resulted in flexural stiffnesses comparable with native tissues (15-220 kPa) with varied mesh sizes and swelling ratios. Hydrogels containing encapsulated valve cells, methacrylated heparin (Hep-MA), or both were substantially less stiff than acellular hydrogels. In conclusion, PEGDA hydrogels are an attractive potential scaffold system for TEHVs because they are not only cytocompatible and modifiable but can also withstand bending deformations. These studies are the first to explore the encapsulation of valvular interstitial cells in pure PEGDA hydrogels as well as to investigate the bending properties of PEGDA gels. © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Authors
Durst, CA; Cuchiara, MP; Mansfield, EG; West, JL; Grande-Allen, KJ
MLA Citation
Durst, CA, Cuchiara, MP, Mansfield, EG, West, JL, and Grande-Allen, KJ. "Flexural characterization of cell encapsulated PEGDA hydrogels with applications for tissue engineered heart valves." Acta Biomaterialia 7.6 (2011): 2467-2476.
PMID
21329770
Source
scival
Published In
Acta Biomaterialia
Volume
7
Issue
6
Publish Date
2011
Start Page
2467
End Page
2476
DOI
10.1016/j.actbio.2011.02.018

A bioresponsive hydrogel tuned to chondrogenesis of human mesenchymal stem cells

Cartilage tissue engineering aims to replace damaged or diseased tissue with a functional regenerate that restores joint function. Scaffolds are used to deliver cells and facilitate tissue development, but they can also interfere with the structural assembly of the cartilage matrix. Biodegradable scaffolds have been proposed as a means to improve matrix deposition and the biomechanical properties of neocartilage. The challenge is designing scaffolds with appropriate degradation rates, ideally such that scaffold degradation is proportional to matrix deposition. In this study, we developed a bioresponsive hydrogel with cell-mediated degradation aligned to the chondrogenic differentiation of human mesenchymal stem cells (hMSCs). We identified matrix metalloproteinase 7 (MMP7) as an enzyme with a temporal expression pattern that corresponded with cartilage development. By embedding MMP7 peptide substrates within a poly(ethylene glycol) diacrylate backbone, we built MMP7-sensitive hydrogels with distinct degradation rates. When MMP7-sensitive scaffolds were compared with nondegradable scaffolds in vitro, photoencapsulated hMSCs produced neocartilage constructs with more extensive collagenous matrices, as demonstrated through immunohistochemistry and biochemical quantification of matrix molecules. Furthermore, these changes translated into an increased dynamic compressive modulus. This work presents a practical strategy for designing biomaterials uniquely tuned to individual biological processes. © FASEB.

Authors
Bahney, CS; Hsu, C-W; Yoo, JU; West, JL; Johnstone, B
MLA Citation
Bahney, CS, Hsu, C-W, Yoo, JU, West, JL, and Johnstone, B. "A bioresponsive hydrogel tuned to chondrogenesis of human mesenchymal stem cells." FASEB Journal 25.5 (2011): 1486-1496.
PMID
21282205
Source
scival
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
25
Issue
5
Publish Date
2011
Start Page
1486
End Page
1496
DOI
10.1096/fj.10-165514

A new era for cancer treatment: Gold-nanoparticle-mediated thermal therapies

Nanotechnology-based cancer treatment approaches potentially provide localized, targeted therapies that aim to enhance efficacy, reduce side effects, and improve patient quality of life. Gold-nanoparticle-mediated hyperthermia shows particular promise in animal studies, and early clinical testing is currently underway. In this article, the rapidly evolving field of gold nanoparticle thermal therapy is reviewed, highlighting recent literature and describing current challenges to clinical translation of the technology. Gold-nanoparticle-mediated thermal therapies represent a promising technology for clinical cancer applications. To treat murine tumors in vivo, gold nanoparticles are intravenously injected, allowed to accumulate in the tumor, and irradiated with an energy source such as near-infrared laser light to thermally ablate the tumor. This review highlights recent literature in the field of gold-nanoparticle-mediated thermal therapies. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Authors
Kennedy, LC; Bickford, LR; Lewinski, NA; Coughlin, AJ; Hu, Y; Day, ES; West, JL; Drezek, RA
MLA Citation
Kennedy, LC, Bickford, LR, Lewinski, NA, Coughlin, AJ, Hu, Y, Day, ES, West, JL, and Drezek, RA. "A new era for cancer treatment: Gold-nanoparticle-mediated thermal therapies." Small 7.2 (2011): 169-183.
PMID
21213377
Source
scival
Published In
Small
Volume
7
Issue
2
Publish Date
2011
Start Page
169
End Page
183
DOI
10.1002/smll.201000134

Nanoshell-mediated photothermal therapy improves survival in a murine glioma model

We are developing a novel treatment for high-grade gliomas using near infrared-absorbing silica-gold nanoshells that are thermally activated upon exposure to a near infrared laser, thereby irreversibly damaging cancerous cells. The goal of this work was to determine the efficacy of nanoshell-mediated photothermal therapy in vivo in murine xenograft models. Tumors were induced in male IcrTac:ICR-Prkdc SCID mice by subcutaneous implantation of Firefly Luciferase-labeled U373 human glioma cells and biodistribution and survival studies were performed. To evaluate nanoparticle biodistribution, nanoshells were delivered intravenously to tumor-bearing mice and after 6, 24, or 48 h the tumor, liver, spleen, brain, muscle, and blood were assessed for gold content by inductively coupled plasma-mass spectrometry (ICP-MS) and histology. Nanoshell concentrations in the tumor increased for the first 24 h and stabilized thereafter. Treatment efficacy was evaluated by delivering saline or nanoshells intravenously and externally irradiating tumors with a near infrared laser 24 h post-injection. Success of treatment was assessed by monitoring tumor size, tumor luminescence, and survival time of the mice following laser irradiation. There was a significant improvement in survival for the nanoshell treatment group versus the control (P < 0.02) and 57% of the mice in the nanoshell treatment group remained tumor free at the end of the 90-day study period. By comparison, none of the mice in the control group survived beyond 24 days and mean survival was only 13.3 days. The results of these studies suggest that nanoshell-mediated photothermal therapy represents a promising novel treatment strategy for malignant glioma. © 2010 Springer Science+Business Media, LLC.

Authors
Day, ES; Thompson, PA; Zhang, L; Lewinski, NA; Ahmed, N; Drezek, RA; Blaney, SM; West, JL
MLA Citation
Day, ES, Thompson, PA, Zhang, L, Lewinski, NA, Ahmed, N, Drezek, RA, Blaney, SM, and West, JL. "Nanoshell-mediated photothermal therapy improves survival in a murine glioma model." Journal of Neuro-Oncology 104.1 (2011): 55-63.
PMID
21110217
Source
scival
Published In
Journal of Neuro-Oncology
Volume
104
Issue
1
Publish Date
2011
Start Page
55
End Page
63
DOI
10.1007/s11060-010-0470-8

Development of bioactive photocrosslinkable fibrous hydrogels

Three-dimensional (3D) fibrous hydrogels were fabricated by blending two photoactive polymers, poly(ethylene glycol) diacrylate (PEGDA) and poly(vinyl alcohol) (PVA), and the resulting solution was electrospun. PEGDA is a commonly used hydrogel material for tissue engineering applications since its interaction with cells can be tuned by crosslinking in a variety of bioactive molecules including peptides and proteins. The PVA in these materials aids in fiber formation and stabilizes the fibrous network when hydrated. The average dry fiber diameter in the hydrogels was 1.02 μm and upon swelling, the fiber diameter increased approximately six-fold. Fibers were stable under cell culture conditions for up to 5 days. The adhesive ligand, RGDS, was readily incorporated into the fibrous network via the conjugation of RGDS to PEG-monoacrylate which was then crosslinked with the fibers. The bioactivity of the fibrous hydrogels was compared with peptide-modified PEGDA-based hydrogels. The two hydrogel materials had similar cell adhesion and viability. Cell morphology on the fibrous hydrogels was dendritic showing a more in vivo like representation, as compared to spread cell morphology on the PEGDA gels. The ability to generate 3D fibrous architectures in hydrogel systems opens up new areas of investigation in cell-material interactions and tissue formation. Copyright © 2011 Wiley Periodicals, Inc.

Authors
Stephens-Altus, JS; Sundelacruz, P; Rowland, ML; West, JL
MLA Citation
Stephens-Altus, JS, Sundelacruz, P, Rowland, ML, and West, JL. "Development of bioactive photocrosslinkable fibrous hydrogels." Journal of Biomedical Materials Research - Part A 98 A.2 (2011): 167-176.
PMID
21548066
Source
scival
Published In
Journal of Biomedical Materials Research Part A
Volume
98 A
Issue
2
Publish Date
2011
Start Page
167
End Page
176
DOI
10.1002/jbm.a.33095

An injectable method for noninvasive spine fusion

Background context: Bone morphogenetic proteins (BMPs) induce bone formation but are difficult to localize, and subsequent diffusion from the site of interest and short half-life reduce the efficacy of the protein. Currently, spine fusion requires stripping, decortications of the transverse processes, and an autograft harvest procedure. Even in combination with BMPs, clinical spinal fusion has a high failure rate, presumably because of difficulties in localizing sufficient levels of BMP. Purpose: The goal was to achieve reliable spine fusion through a single injection of a cell-based gene therapy system without the need for any surgical intervention. Study design: Eighty-seven immunodeficient (n=44) and immune-competent (n=43) mice were injected along the paraspinous musculature to achieve rapid induction of heterotopic ossification (HO) and ultimately spinal arthrodesis. Methods: Immunodeficient and immune-competent mice were injected with fibroblasts, transduced with an adenoviral vector to express BMP2, along the paraspinous musculature. Bone formation was evaluated via radiographs, microcomputed tomography, and biomechanical analysis. Results: ew bridging bone between the vertebrae and the fusion to adjacent skeletal bone was obtained as early as 2 weeks. Reduction in spine flexion-extension also occurred as early as 2 weeks after injection of the gene therapy system, with greater than 90% fusion by 4 weeks in all animals regardless of their genetic background. Conclusions: Injection of our cell-based system into the paraspinous musculature induces spinal fusion that is dependent neither on the cell type nor on the immune status. These studies are the first to harness HO in an immune-competent model as a noninvasive injectable system for clinically relevant spinal fusion and may one day impact human spinal arthrodesis. © 2011 Elsevier Inc. All rights reserved.

Authors
Olabisi, RM; Lazard, Z; Heggeness, MH; Moran, KM; Hipp, JA; Dewan, AK; Davis, AR; West, JL; Olmsted-Davis, EA
MLA Citation
Olabisi, RM, Lazard, Z, Heggeness, MH, Moran, KM, Hipp, JA, Dewan, AK, Davis, AR, West, JL, and Olmsted-Davis, EA. "An injectable method for noninvasive spine fusion." Spine Journal 11.6 (2011): 545-556.
PMID
21292563
Source
scival
Published In
The Spine Journal
Volume
11
Issue
6
Publish Date
2011
Start Page
545
End Page
556
DOI
10.1016/j.spinee.2010.12.011

Microcontact printing for co-patterning cells and viruses for spatially controlled substrate-mediated gene delivery

Spatial organization of gene expression is a crucial element in the development of complex native tissues, and the capacity to achieve spatially controlled gene expression profiles in a tissue engineering construct is still a considerable challenge. To give tissue engineers the ability to design specific, spatially organized gene expression profiles in an engineered construct, we have investigated the use of microcontact printing to pattern recombinant adeno-associated virus (AAV) vectors on a two dimensional surface as a first proof-of-concept study. AAV is a highly safe, versatile, stable, and easy-to-use gene delivery vector, making it an ideal choice for this application. We tested the suitability of four chemical surfaces (-CH 3, -COOH, -NH2, and -OH) to mediate localized substrate-mediated gene delivery. First, polydimethylsiloxane stamps were used to create microscale patterns of various self-assembled monolayers on gold-coated glass substrates. Next, AAV particles carrying genes of interest and human fibronectin (HFN) were immobilized on the patterned substrates, creating a spatially organized arrangement of gene delivery vectors. Immunostaining studies reveal that -CH3 and -NH2 surfaces result in the most successful adsorption of both AAV and HFN. Lastly, HeLa cells were used to analyze viral transduction and spatial localization of gene expression. We find that -CH3, -COOH, and -NH2 surfaces support complete uniform cell coverage with high gene expression. Notably, we observe a synergistic effect between HFN and AAV for substrate-mediated gene delivery. Our flexible platform should allow for the specific patterning of various gene and shRNA cassettes, resulting in spatially defined gene expression profiles that may enable the generation of highly functional tissue. © 2011 The Royal Society of Chemistry.

Authors
McConnell, KI; Slater, JH; Han, A; West, JL; Suh, J
MLA Citation
McConnell, KI, Slater, JH, Han, A, West, JL, and Suh, J. "Microcontact printing for co-patterning cells and viruses for spatially controlled substrate-mediated gene delivery." Soft Matter 7.10 (2011): 4993-5001.
Source
scival
Published In
Soft Matter
Volume
7
Issue
10
Publish Date
2011
Start Page
4993
End Page
5001
DOI
10.1039/c0sm01209b

Fabrication of multifaceted micropatterned surfaces with laser scanning lithography

The implementation of engineered surfaces presenting micrometer-sized patterns of cell adhesive ligands against a biologically inert background has led to numerous discoveries in fundamental cell biology. While existing surface patterning strategies allow patterning of a single ligand, it is still challenging to fabricate surfaces displaying multiple patterned ligands. To address this issue we implemented laser scanning lithography (LSL), a laser-based thermal desorption technique, to fabricate multifaceted, micropatterned surfaces that display independent arrays of subcellular-sized patterns of multiple adhesive ligands with each ligand confined to its own array. We demonstrate that LSL is a highly versatile "maskless" surface patterning strategy that provides the ability to create patterns with features ranging from 460 nm to 100 μm, topography ranging from -1 to 17 nm, and to fabricate both stepwise and smooth ligand surface density gradients. As validation for their use in cell studies, surfaces presenting orthogonally interwoven arrays of 1 μm × 8 μm elliptical patterns of Gly-Arg-Gly-Asp-terminated alkanethiol self-assembled monolayers and human plasma fibronectin are produced. Human umbilical vein endothelial cells cultured on these multifaceted surfaces form adhesion sites to both ligands simultaneously and utilize both ligands for lamella formation during migration. The ability to create multifaceted, patterned surfaces with tight control over pattern size, spacing, and topography provides a platform to simultaneously investigate the complex interactions of extracellular matrix geometry, biochemistry, and topography on cell adhesion and downstream cell behavior. A laser-based patterning strategy for the fabrication of multifaceted, micropatterned surfaces that display patterned arrays of multiple cell adhesive ligands with each ligand confined to its own array is presented. Cells cultured on these surfaces display concurrent adhesion to both ligands simultaneously and utilize both ligands for lamella formation during migration. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Authors
Slater, JH; Miller, JS; Yu, SS; West, JL
MLA Citation
Slater, JH, Miller, JS, Yu, SS, and West, JL. "Fabrication of multifaceted micropatterned surfaces with laser scanning lithography." Advanced Functional Materials 21.15 (2011): 2876-2888.
Source
scival
Published In
Advanced Functional Materials
Volume
21
Issue
15
Publish Date
2011
Start Page
2876
End Page
2888
DOI
10.1002/adfm.201100297

Cell-based gene therapy for repair of critical size defects in the rat fibula

More than a decade has passed since the first experiments using adenovirus-transduced cells expressing bone morphogenetic protein 2 were performed for the synthesis of bone. Since this time, the field of bone gene therapy has tackled many issues surrounding safety and efficacy of this type of strategy. We present studies examining the parameters of the timing of bone healing, and remodeling when heterotopic ossification (HO) is used for bone fracture repair using an adenovirus gene therapy approach. We use a rat fibula defect, which surprisingly does not heal even when a simple fracture is introduced. In this model, the bone quickly resorbs most likely due to the non-weight bearing nature of this bone in rodents. Using our gene therapy system robust HO can be introduced at the targeted location of the defect resulting in bone repair. The HO and resultant bone healing appeared to be dose dependent, based on the number of AdBMP2-transduced cells delivered. Interestingly, the HO undergoes substantial remodeling, and assumes the size and shape of the missing segment of bone. However, in some instances we observed some additional bone associated with the repair, signifying that perhaps the forces on the newly forming bone are inadequate to dictate shape. In all cases, the HO appeared to fuse into the adjacent long bone. The data collectively indicates that the use of BMP2 gene therapy strategies may vary depending on the location and nature of the defect. Therefore, additional parameters should be considered when implementing such strategies. Copyright © 2011 Wiley-Liss, Inc.

Authors
Lazard, ZW; Heggeness, MH; Hipp, JA; Sonnet, C; Fuentes, AS; Nistal, RP; Davis, AR; Olabisi, RM; West, JL; Olmsted-Davis, EA
MLA Citation
Lazard, ZW, Heggeness, MH, Hipp, JA, Sonnet, C, Fuentes, AS, Nistal, RP, Davis, AR, Olabisi, RM, West, JL, and Olmsted-Davis, EA. "Cell-based gene therapy for repair of critical size defects in the rat fibula." Journal of Cellular Biochemistry 112.6 (2011): 1563-1571.
PMID
21344484
Source
scival
Published In
Journal of Cellular Biochemistry
Volume
112
Issue
6
Publish Date
2011
Start Page
1563
End Page
1571
DOI
10.1002/jcb.23068

The promotion of microvasculature formation in poly(ethylene glycol) diacrylate hydrogels by an immobilized VEGF-mimetic peptide

Microvascularization of tissue engineered constructs was achieved by utilizing a VEGF-mimicking peptide, QK, covalently bound to a poly(ethylene glycol) hydrogel matrix. The 15-amino acid peptide, developed by D'Andrea et al., was modified with a PEG-succinimidyl ester linker on the N-terminus of the peptide, then photocrosslinked onto the surface or throughout PEG hydrogels. PEGylation of the peptide increased its solubility and bioactivity, as evidenced by endothelial cell proliferation. PEG-QK showed equal or superior ability to promote angiogenesis in vitro, on the surface of hydrogels and within three-dimensional collagenase-degradable hydrogels, compared to RGDS only or PEG-VEGF hydrogels. Endothelial cells were shown to form tubule structures, migrate, and make cell-cell contacts in response to covalently-bound PEG-QK. In vivo in a mouse cornea micropocket angiogenesis assay, PEG-QK hydrogels promoted more complete coverage of host microvasculature within the hydrogel. PEG-QK was shown to enhance vessel branch points and vessel density as well as space filling properties of fractal dimension and lacunarity. This report shows the ability to promote angiogenesis in tissue engineered constructs using a covalently-bound small peptide rather than a large protein and may point to an advance in designing biomimetic cellular environments. © 2011 Elsevier Ltd.

Authors
Leslie-Barbick, JE; Saik, JE; Gould, DJ; Dickinson, ME; West, JL
MLA Citation
Leslie-Barbick, JE, Saik, JE, Gould, DJ, Dickinson, ME, and West, JL. "The promotion of microvasculature formation in poly(ethylene glycol) diacrylate hydrogels by an immobilized VEGF-mimetic peptide." Biomaterials 32.25 (2011): 5782-5789.
PMID
21612821
Source
scival
Published In
Biomaterials
Volume
32
Issue
25
Publish Date
2011
Start Page
5782
End Page
5789
DOI
10.1016/j.biomaterials.2011.04.060

Cathepsin K-sensitive poly(ethylene glycol) hydrogels for degradation in response to bone resorption

We propose a new strategy of biomaterial design to achieve selective cellular degradation by the incorporation of cathepsin K-degradable peptide sequences into a scaffold structure so that scaffold biodegradation can be induced at the end of the bone formation process. Poly(ethylene glycol) diacrylate (PEGDA) hydrogels were used as a model biomaterial system in this study. A cathepsin K-sensitive peptide, GGGMGPSGPWGGK (GPSG), was synthesized and modified with acryloyl-PEG-succinimidyl carbonate to produce a cross-linkable cathepsin K-sensitive polymer that can be used to form a hydrogel. Specificity of degradation of the GPSG hydrogels was tested with cathepsin K and proteinase K as a positive control, with both resulting in significant degradation compared to incubation with nonspecific collagenases over a 24-h time period. No degradation was observed when the hydrogels were incubated with plasmin or control buffers. Cell-induced degradation was evaluated by seeding differentiated MC3T3-E1 osteoblasts and RAW264.7 osteoclasts on GPSG hydrogels that were also modified with the cell adhesion peptide RGDS. Resulting surface features and resorption pits were analyzed by differential interference contrast (DIC) and fluorescent images obtained with confocal microscopy. Results from both analyses demonstrated that GPSG hydrogels can be degraded specifically in response to osteoclast attachment but not in response to osteoblasts. In summary, we have demonstrated that by incorporating a cathepsin K-sensitive peptide into a synthetic polymer structure, we can generate biomaterials that specifically respond to cues from the natural process of bone remodeling. © 2011 Wiley Periodicals, Inc.

Authors
Hsu, C-W; Olabisi, RM; Olmsted-Davis, EA; Davis, AR; West, JL
MLA Citation
Hsu, C-W, Olabisi, RM, Olmsted-Davis, EA, Davis, AR, and West, JL. "Cathepsin K-sensitive poly(ethylene glycol) hydrogels for degradation in response to bone resorption." Journal of Biomedical Materials Research - Part A 98 A.1 (2011): 53-62.
PMID
21523904
Source
scival
Published In
Journal of Biomedical Materials Research Part A
Volume
98 A
Issue
1
Publish Date
2011
Start Page
53
End Page
62
DOI
10.1002/jbm.a.33076

Covalently immobilized platelet-derived growth factor-BB promotes angiogenesis in biomimetic poly(ethylene glycol) hydrogels

The field of tissue engineering is severely limited by a lack of microvascularization in tissue engineered constructs. Biomimetic poly(ethylene glycol) hydrogels containing covalently immobilized platelet-derived growth factor BB (PDGF-BB) were developed to promote angiogenesis. Poly(ethylene glycol) hydrogels resist protein absorption and subsequent non-specific cell adhesion, thus providing a "blank slate", which can be modified through the incorporation of cell adhesive ligands and growth factors. PDGF-BB is a key angiogenic protein able to support neovessel stabilization by inducing functional anastomoses and recruiting pericytes. Due to the widespread effects of PDGF in the body and a half-life of only 30 min in circulating blood, immobilization of PDGF-BB may be necessary. In this work bioactive, covalently immobilized PDGF-BB was shown to induce tubulogenesis on two-dimensional modified surfaces, migration in three-dimensional (3D) degradable hydrogels and angiogenesis in a mouse cornea micropocket angiogenesis assay. Covalently immobilized PDGF-BB was also used in combination with covalently immobilized fibroblast growth factor-2, which led to significantly increased endothelial cell migration in 3D degradable hydrogels compared with the presentation of each factor alone. When a co-culture of endothelial cells and mouse pericyte precursor 10T1/2 cells was seeded onto modified surfaces tubule formation was independent of surface modifications with covalently immobilized growth factors. Furthermore, the combination of soluble PDGF-BB and immobilized PDGF-BB induced a more robust vascular response compared with soluble PDGF-BB alone when implanted into an in vivo mouse cornea micropocket angiogenesis assay. Based on these results, we believe bioactive hydrogels can be tailored to improve the formation of functional microvasculature for tissue engineering. © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Authors
Saik, JE; Gould, DJ; Watkins, EM; Dickinson, ME; West, JL
MLA Citation
Saik, JE, Gould, DJ, Watkins, EM, Dickinson, ME, and West, JL. "Covalently immobilized platelet-derived growth factor-BB promotes angiogenesis in biomimetic poly(ethylene glycol) hydrogels." Acta Biomaterialia 7.1 (2011): 133-143.
PMID
20801242
Source
scival
Published In
Acta Biomaterialia
Volume
7
Issue
1
Publish Date
2011
Start Page
133
End Page
143
DOI
10.1016/j.actbio.2010.08.018

Protein-patterned hydrogels: Customized cell microenvironments

Wylie et al. have demonstrate the simultaneous immobilization of multiple proteins in hydrogels with three-dimensional (3D) spatial control. The growth of cells in 3D gels made of collagen or reconstituted extracellular matrix (ECM) proteins has shown that cellular responses in such systems are different from observations made on polystyrene surfaces. By using two-photon chemistry, Wylie and colleagues show the feasibility of patterning two proteins, the stem-cell differentiation factors sonic hedgehog (SHH) and ciliary neurotrophic factor (CNTF), as opposed to the shorter bioactive peptides that have been previously immobilized in two-photon patterning studies. As a result of this experiment, stacks of patterned agarose hydrogel layers are fabricated and that the pair of fusion proteins barstar SSH and biotin CNTF remain bioactive after immobilization.

Authors
West, JL
MLA Citation
West, JL. "Protein-patterned hydrogels: Customized cell microenvironments." Nature Materials 10.10 (2011): 727-729.
PMID
21941268
Source
scival
Published In
Nature Materials
Volume
10
Issue
10
Publish Date
2011
Start Page
727
End Page
729
DOI
10.1038/nmat3132

Thermally responsive polymer-nanoparticle composites for biomedical applications

Thermally responsive polymer-metal nanoparticle composites couple the ability of certain metal nanoparticles to convert external stimuli to heat with polymers that display sharp property changes in response to temperature changes, allowing for external control over polymer properties. These systems have been investigated for a variety of biomedical applications, including drug delivery, microfluidic valve control, and cancer therapy. This article focuses on three different size scales of this system: bulk systems (>1mm), nano- or microscale systems, and individual particle coatings. These composite systems will continue to be widely researched in the future for their vast potential in various biomedical applications. © 2011 John Wiley & Sons, Inc.

Authors
Strong, LE; West, JL
MLA Citation
Strong, LE, and West, JL. "Thermally responsive polymer-nanoparticle composites for biomedical applications." Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 3.3 (2011): 307-317.
PMID
21384563
Source
scival
Published In
Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology
Volume
3
Issue
3
Publish Date
2011
Start Page
307
End Page
317
DOI
10.1002/wnan.138

Biomimetic hydrogels with immobilized EphrinA1 for therapeutic angiogenesis

The formation of a microvasculature is regulated in large part by cell-cell interactions. Ephrins and their Eph receptors mediate cell adhesion, repulsion, and migration, all critical processes in angiogenesis.(1)Here we use a covalently immobilized ephrinA1, conjugated to poly(ethylene glycol), to induce vessel formation both in vitro and in vivo in poly(ethylene glycol) diacrylate (PEGDA) hydrogels. Human umbilical vein endothelial cell (HUVEC) tubulogenesis in matrix metalloproteinase-sensitive hydrogels was visualized from 6 h to 7 days in response to three different concentrations of PEG-ephrinA1. The deposition of extracellular matrix proteins collagen IV and laminin that stabilize tubule formation were imaged, quantified, and found to be dependent on PEG-ephrinA1 concentration. To confirm the importance of the EphA2-ephrinA1 interaction in tubule formation, soluble EphA2 was used to disrupt the EphA2-ephrinA1 interaction between a coculture of HUVEC and human brain vascular pericyte cells. HUVECs seeded onto PEGDA hydrogels displayed a dose-dependent reduction in tubule formation in response to the soluble EphA2. Finally, hydrogels with releasable platelet-derived growth factor (PDGF), immobilized RGDS, and covalently immobilized PEG-ephrinA1 were implanted into the mouse cornea micropocket. These hydrogels induced a more robust vascular response with an increase in vessel density as compared with hydrogels with releasable PDGF alone. As such, PEG-ephrinA1 may represent a promising molecule to regulate cell adhesion and migration for formation of a microvasculature in tissue-engineered constructs. © 2011 American Chemical Society.

Authors
Saik, JE; Gould, DJ; Keswani, AH; Dickinson, ME; West, JL
MLA Citation
Saik, JE, Gould, DJ, Keswani, AH, Dickinson, ME, and West, JL. "Biomimetic hydrogels with immobilized EphrinA1 for therapeutic angiogenesis." Biomacromolecules 12.7 (2011): 2715-2722.
PMID
21639150
Source
scival
Published In
Biomacromolecules
Volume
12
Issue
7
Publish Date
2011
Start Page
2715
End Page
2722
DOI
10.1021/bm200492h

Development and optimization of a dual-photoinitiator, emulsion-based technique for rapid generation of cell-laden hydrogel microspheres

A growing number of clinical trials explore the use of cell-based therapies for the treatment of disease and restoration of damaged tissue; however, limited cell survival and engraftment remains a significant challenge. As the field continues to progress, microencapsulation strategies are proving to be a valuable tool for protecting and supporting these cell therapies while preserving minimally invasive delivery. This work presents a novel, dual-photoinitiator technique for encapsulation of cells within hydrogel microspheres. A desktop vortexer was used to generate an emulsion of poly(ethylene glycol) diacrylate (PEGDA) or PEGDA-based precursor solution in mineral oil. Through an optimized combination of photoinitiators added to both the aqueous and the oil phase, rapid gelation of the suspended polymer droplets was achieved. The photoinitiator combination provided superior cross-linking consistency and greater particle yield, and required lower overall initiator concentrations compared with a single initiator system. When cells were combined with the precursor solution, these benefits translated to excellent microencapsulation yield with 60-80% viability for the tested cell types. It was further shown that the scaffold material could be modified with cell-adhesive peptides to be used as surface-seeded microcarriers, or additionally with enzymatically degradable sequences to support three-dimensional spreading, migration and long-term culture of encapsulated cells. Three cell lines relevant to neural stem cell therapies are demonstrated here, but this technology is adaptable, scalable and easy to implement with standard laboratory equipment, making it a useful tool for advancing the next generation of cell-based therapeutics.

Authors
Franco, CL; Price, J; West, JL
MLA Citation
Franco, CL, Price, J, and West, JL. "Development and optimization of a dual-photoinitiator, emulsion-based technique for rapid generation of cell-laden hydrogel microspheres." Acta Biomaterialia 7.9 (2011): 3267-3276.
PMID
21704198
Source
scival
Published In
Acta Biomaterialia
Volume
7
Issue
9
Publish Date
2011
Start Page
3267
End Page
3276
DOI
10.1016/j.actbio.2011.06.011

Sustained Delivery of Nitric Oxide from Poly(ethylene glycol) Hydrogels Enhances Endothelialization in a Rat Carotid Balloon Injury Model

The continuing high incidence of vascular disease is leading to a greater need for interventional therapies and vascular prostheses. Nitric oxide (NO), which has been heavily investigated in recent years as an important biological mediator, is presented in this work as a sustained localized therapeutic for vascular disorders, specifically in the prevention of restenosis. NO-releasing PEG hydrogels were applied to the outer surfaces of carotid arteries following balloon denudation in a rat animal model. NO was allowed to diffuse into the vessel, and intimal thickening, as assessed after 2 and 28 days, was almost fully eliminated, showing an approximate 90% decrease. Meanwhile, endothelial cell migration and proliferation into the damaged vessel sections were observed. These results signify that these materials are suitable to prevent intimal hyperplasia and induce endothelialization in vivo, making these NO-releasing hydrogels an ideal candidate for incorporation into blood-contacting devices for the prevention of restenosis. © 2011 Biomedical Engineering Society.

Authors
Taite, LJ; West, JL
MLA Citation
Taite, LJ, and West, JL. "Sustained Delivery of Nitric Oxide from Poly(ethylene glycol) Hydrogels Enhances Endothelialization in a Rat Carotid Balloon Injury Model." Cardiovascular Engineering and Technology 2.2 (2011): 113-123.
Source
scival
Published In
Cardiovascular Engineering and Technology
Volume
2
Issue
2
Publish Date
2011
Start Page
113
End Page
123
DOI
10.1007/s13239-011-0040-z

Histogenesis in Three-dimensional Scaffolds

The need for replacement tissues and organs is influencing tissue engineers to develop materials and strategies capable of generating biologically functional substitutes. Researchers seek to develop a scaffold material that can support viability of the appropriate cell type while acting as a temporary substitute for the extracellular matrix. Over time this surrogate matrix will ideally be replaced by functional replacement tissue. A variety of cell types are investigated for regeneration applications including differentiated cells, adult-derived stem cells, and embryonic stem cells. There are three types of mature cells: autologous, allogeneic, and xenogeniec. Allogeneic cells are harvested from healthy adult donor organs and then expanded in vitro. Scaffolds with allogeneic cells are subject to immune rejection but these cells are successful in skin regeneration for burn patients. Autologous cells biopsied from a patient, expanded in vitro, and then seeded onto a tissue scaffold prior to re-implantation into the same individual are generally viewed as the ideal replacement in terms of compatibility. In most types of synthetic materials, successful histogenesis requires a porous microstructure. Scaffold porosity, pore size, and the overall pore structure all have important effects upon tissue formation and infiltration into biomaterial constructs. Interconnecting pores facilitate the loading of cells into scaffold materials while the increased internal surface area provides sites for attachment and spreading. © 2011 Elsevier Inc. All rights reserved.

Authors
McHale, MK; Bergmann, NM; West, JL
MLA Citation
McHale, MK, Bergmann, NM, and West, JL. "Histogenesis in Three-dimensional Scaffolds." Principles of Regenerative Medicine (2011): 675-691.
Source
scival
Published In
Principles of Regenerative Medicine
Publish Date
2011
Start Page
675
End Page
691
DOI
10.1016/B978-0-12-381422-7.10037-9

YBCO superconducting tapes patterned using microcontact printing

Authors
Kim, M; Galstyan, E; Bryan, WW; Cuchiara, MP; West, JL; Freyhardt, HC; Jacobson, AJ; Lee, TR
MLA Citation
Kim, M, Galstyan, E, Bryan, WW, Cuchiara, MP, West, JL, Freyhardt, HC, Jacobson, AJ, and Lee, TR. "YBCO superconducting tapes patterned using microcontact printing." ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 239 (March 2010). (Academic Article)
Source
manual
Published In
ACS National Meeting Book of Abstracts
Volume
239
Publish Date
2010

Synthetic materials in the study of cell response to substrate rigidity

While it has long been understood that cells can sense and respond to a variety of stimuli, including soluble and insoluble factors, light, and externally applied mechanical stresses, the extent to which cells can sense and respond to the mechanical properties of their environment has only recently begun to be studied. Cell response to substrate stiffness has been suggested to play an important role in processes ranging from developmental morphogenesis to the pathogenesis of disease states and may have profound implications for cell and tissue culture and tissue engineering. Given the importance of this phenomenon, there is a clear need for systems for cell study in which substrate mechanics can be carefully defined and varied independently of biochemical and other signals. This review will highlight past work in the field of cell response to substrate rigidity as well as areas for future study. © 2009 Biomedical Engineering Society.

Authors
Nemir, S; West, JL
MLA Citation
Nemir, S, and West, JL. "Synthetic materials in the study of cell response to substrate rigidity." Annals of Biomedical Engineering 38.1 (2010): 2-20.
PMID
19816774
Source
scival
Published In
Annals of Biomedical Engineering
Volume
38
Issue
1
Publish Date
2010
Start Page
2
End Page
20
DOI
10.1007/s10439-009-9811-1

Antibody-conjugated gold-gold sulfide nanoparticles as multifunctional agents for imaging and therapy of breast cancer

The goal of this study was to develop near-infrared (NIR) resonant gold-gold sulfide nanoparticles (GGS-NPs) as dual contrast and therapeutic agents for cancer management via multiphoton microscopy followed by higher intensity photoablation. We demonstrate that GGS-NPs exposed to a pulsed, NIR laser exhibit two-photon induced photoluminescence that can be utilized to visualize cancerous cells in vitro. When conjugated with anti-HER2 antibodies, these nanoparticles specifically bind SK-BR-3 breast carcinoma cells that overexpress the HER2 receptor, enabling the cells to be imaged via multiphoton microscopy with an incident laser power of 1 mW. Higher excitation power (50 mW) could be employed to induce thermal damage to the cancerous cells, producing extensive membrane blebbing within seconds leading to cell death. GGS-NPs are ideal multifunctional agents for cancer management because they offer the ability to pinpoint precise treatment sites and perform subsequent thermal ablation in a single setting. © 2010 Day et al, publisher and licensee Dove Medical Press Ltd.

Authors
Day, ES; Bickford, LR; Slater, JH; Riggall, NS; Drezek, RA; West, JL
MLA Citation
Day, ES, Bickford, LR, Slater, JH, Riggall, NS, Drezek, RA, and West, JL. "Antibody-conjugated gold-gold sulfide nanoparticles as multifunctional agents for imaging and therapy of breast cancer." International Journal of Nanomedicine 5.1 (2010): 445-454.
PMID
20957166
Source
scival
Published In
International journal of nanomedicine
Volume
5
Issue
1
Publish Date
2010
Start Page
445
End Page
454

Three-dimensional photolithographic patterning of multiple bioactive ligands in poly(ethylene glycol) hydrogels

The biomaterials community is faced with the challenge of imitating a vastly complex, physiological tissue environment. While cellular systems towards this end have been traditionally studied in two dimensions (2D), most cells require three-dimensional (3D) cues to produce a physiologically relevant response. Two-photon absorption laser scanning lithography (TPA-LSL) may be applied to photosensitive hydrogel systems to engineer heterogeneous, 3D microenvironments consisting of precisely patterned bioactive signals. In this work, we have developed new operating parameters and system capabilities for TPA-LSL through the patterning of fluorescently labeled monoacrylate PEG-RGDS within PEG-DA hydrogels. Specifically, we have demonstrated a flexible pattern size range, with features ranging from 1 m to nearly 1 mm. We have also shown patterns of differing concentrations of the cell adhesive ligand RGDS and correlated observed RGDS fluorescence with laser scan speed and intensity. Finally, we have micropatterned multiple, unique bioactive ligands into distinct, 3D forms within a single hydrogel. The results presented here have significantly developed the capabilities of the TPA-LSL micropatterning technique to allow for the fabrication of heterogeneous, 3D cellular microenvironments, which should prove highly useful for future biomimetic applications. © 2010 The Royal Society of Chemistry.

Authors
Hoffmann, JC; West, JL
MLA Citation
Hoffmann, JC, and West, JL. "Three-dimensional photolithographic patterning of multiple bioactive ligands in poly(ethylene glycol) hydrogels." Soft Matter 6.20 (2010): 5056-5063.
Source
scival
Published In
Soft Matter
Volume
6
Issue
20
Publish Date
2010
Start Page
5056
End Page
5063
DOI
10.1039/c0sm00140f

PEGDA hydrogels with patterned elasticity: Novel tools for the study of cell response to substrate rigidity

The ability of cells to migrate in response to mechanical gradients (durotaxis) and differential cell behavior in adhesion, spreading, and proliferation in response to substrate rigidity are key factors both in tissue engineering, in which materials must be selected to provide the appropriate mechanical signals, and in studies of mechanisms of diseases such as cancer and atherosclerosis, in which changes in tissue stiffness may inform cell behavior. Using poly(-ethylene glycol) diacrylate hydrogels with varying polymer chain length and photolithographic patterning techniques, we are able to provide substrates with spatially patterned, tunable mechanical properties in both gradients and distinct patterns. The hydrogels can be patterned to produce anisotropic structures and exhibit patterned strain under mechanical loading. These hydrogels may be used to study cell response to substrate rigidity in both two and three dimensions and can also be used as a scaffold in tissueengineering applications. © 2009 Wiley Periodicals, Inc.

Authors
Nemir, S; Hayenga, HN; West, JL
MLA Citation
Nemir, S, Hayenga, HN, and West, JL. "PEGDA hydrogels with patterned elasticity: Novel tools for the study of cell response to substrate rigidity." Biotechnology and Bioengineering 105.3 (2010): 636-644.
PMID
19816965
Source
scival
Published In
Biotechnology & Bioengineering
Volume
105
Issue
3
Publish Date
2010
Start Page
636
End Page
644
DOI
10.1002/bit.22574

Hydrogel microsphere encapsulation of a cell-based gene therapy system increases cell survival of injected cells, transgene expression, and bone volume in a model of heterotopic ossification

Bone morphogenetic proteins (BMPs) are well known for their osteoinductive activity, yet harnessing this capacity remains a high-priority research focus. We present a novel technology that delivers high BMP-2 levels at targeted locations for rapid endochondral bone formation, enhancing our preexisting cell-based gene therapy system by microencapsulating adenovirus-transduced cells in nondegradable poly(ethylene glycol) diacrylate (PEGDA) hydrogels before intramuscular delivery. This study evaluates the in vitro and in vivo viability, gene expression, and bone formation from transgenic fibroblasts encapsulated in PEGDA microspheres. Fluorescent viability and cytotoxicity assays demonstrated >95% viability in microencapsulated cells. ELISA and alkaline phosphatase assays established that BMP-2 secretion and specific activity from microencapsulated AdBMP2-transduced fibroblasts were not statistically different from monolayer. Longitudinal transgene expression studies of AdDsRed-transduced fibroblasts, followed through live animal optical fluorescent imaging, showed that microencapsulated cells expressed longer than unencapsulated cells. When comparable numbers of microencapsulated AdBMP2-transduced cells were intramuscularly injected into mice, microcomputed tomography evaluation demonstrated that the resultant heterotopic bone formation was approximately twice the volume of unencapsulated cells. The data suggest that microencapsulation protects cells and prolongs and spatially distributes transgene expression. Thus, incorporation of PEGDA hydrogels significantly advances current gene therapy bone repair approaches. © 2010 Mary Ann Liebert, Inc.

Authors
Olabisi, RM; Lazard, ZW; Franco, CL; Hall, MA; Kwon, SK; Sevick-Muraca, EM; Hipp, JA; Davis, AR; Olmsted-Davis, EA; West, JL
MLA Citation
Olabisi, RM, Lazard, ZW, Franco, CL, Hall, MA, Kwon, SK, Sevick-Muraca, EM, Hipp, JA, Davis, AR, Olmsted-Davis, EA, and West, JL. "Hydrogel microsphere encapsulation of a cell-based gene therapy system increases cell survival of injected cells, transgene expression, and bone volume in a model of heterotopic ossification." Tissue Engineering - Part A 16.12 (2010): 3727-3736.
PMID
20673027
Source
scival
Published In
Tissue Engineering, Part A
Volume
16
Issue
12
Publish Date
2010
Start Page
3727
End Page
3736
DOI
10.1089/ten.tea.2010.0234

Biomimetic hydrogels with pro-angiogenic properties

To achieve the task of fabricating functional tissues, scaffold materials that can be sufficiently vascularized to mimic functionality and complexity of native tissues are yet to be developed. Here, we report development of synthetic, biomimetic hydrogels that allow the rapid formation of a stable and mature vascular network both in vitro and in vivo. Hydrogels were fabricated with integrin binding sites and protease-sensitive substrates to mimic the natural provisional extracellular matrices, and endothelial cells cultured in these hydrogels organized into stable, intricate networks of capillary-like structures. The resulting structures were further stabilized by recruitment of mesenchymal progenitor cells that differentiated into a smooth muscle cell lineage and deposited collagen IV and laminin in vitro. In addition, hydrogels transplanted into mouse corneas were infiltrated with host vasculature, resulting in extensive vascularization with functional blood vessels. These results indicate that these hydrogels may be useful for applications in basic biological research, tissue engineering, and regenerative medicine. © 2010 Elsevier Ltd. All rights reserved.

Authors
Moon, JJ; Saik, JE; Poché, RA; Leslie-Barbick, JE; Lee, S-H; Smith, AA; Dickinson, ME; West, JL
MLA Citation
Moon, JJ, Saik, JE, Poché, RA, Leslie-Barbick, JE, Lee, S-H, Smith, AA, Dickinson, ME, and West, JL. "Biomimetic hydrogels with pro-angiogenic properties." Biomaterials 31.14 (2010): 3840-3847.
PMID
20185173
Source
scival
Published In
Biomaterials
Volume
31
Issue
14
Publish Date
2010
Start Page
3840
End Page
3847
DOI
10.1016/j.biomaterials.2010.01.104

Multilayer microfluidic PEGDA hydrogels

Development of robust 3D tissue analogs in vitro is limited by passive, diffusional mass transport. Perfused microfluidic tissue engineering scaffolds hold the promise to improve mass transport limitations and promote the development of complex, metabolically dense, and clinically relevant tissues. We report a simple and robust multilayer replica molding technique in which poly(dimethylsiloxane) (PDMS) and poly(ethylene glycol) diacrylate (PEGDA) are serially replica molded to develop microfluidic PEGDA hydrogel networks embedded within independently fabricated PDMS housings. We demonstrate the ability to control solute-scaffold effective diffusivity as a function of solute molecular weight and hydrogel concentration. Within cell laden microfluidic hydrogels, we demonstrate increased cellular viability in perfused hydrogel systems compared to static controls. We observed a significant increase in cell viability at all time points greater than zero at distances up to 1 mm from the perfused channel. Knowledge of spatiotemporal mass transport and cell viability gradients provides useful engineering design parameters necessary to maximize overall scaffold viability and metabolic density. This work has applications in the development of hydrogels as in vitro diagnostics and ultimately as regenerative medicine based therapeutics. © 2010 Elsevier Ltd.

Authors
Cuchiara, MP; Allen, ACB; Chen, TM; Miller, JS; West, JL
MLA Citation
Cuchiara, MP, Allen, ACB, Chen, TM, Miller, JS, and West, JL. "Multilayer microfluidic PEGDA hydrogels." Biomaterials 31.21 (2010): 5491-5497.
PMID
20447685
Source
scival
Published In
Biomaterials
Volume
31
Issue
21
Publish Date
2010
Start Page
5491
End Page
5497
DOI
10.1016/j.biomaterials.2010.03.031

Near-infrared-resonant gold/gold sulfide nanoparticles as a photothermal cancer therapeutic agent

The development and optimization of near-infrared (NlR)-absorbing nanoparticles for use as photothermal cancer therapeutic agents has been ongoing. This work exploits the properties of gold/gold sulfide NIR-absorbing nanoparticles (≈35-55nm) that provide higher absorption (98% absorption and 2% scattering for gold/gold sulfide versus 70% absorption and 30% scattering for gold/silica nanoshells) as well as potentially better tumor penetration. The ability to ablate tumor cells in vitro and efficacy for photothermal cancer therapy is demonstrated, and an in vivo model shows significantly increased long-term, tumor-free survival. Furthermore, enhanced circulation and biodistribution is observed in vivo. This class of NlR-absorbing nanoparticles has the potential to improve upon photothermal tumor ablation for cancer therapy. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Authors
Gobin, AM; Watkins, EM; Quevedo, E; Colvin, VL; West, JL
MLA Citation
Gobin, AM, Watkins, EM, Quevedo, E, Colvin, VL, and West, JL. "Near-infrared-resonant gold/gold sulfide nanoparticles as a photothermal cancer therapeutic agent." Small 6.6 (2010): 745-752.
PMID
20183810
Source
scival
Published In
Small
Volume
6
Issue
6
Publish Date
2010
Start Page
745
End Page
752
DOI
10.1002/smll.200901557

The mouse cornea as a transplantation site for live imaging of engineered tissue constructs

Authors
Poché, RA; Saik, JE; West, JL; Dickinson, ME
MLA Citation
Poché, RA, Saik, JE, West, JL, and Dickinson, ME. "The mouse cornea as a transplantation site for live imaging of engineered tissue constructs." Cold Spring Harbor Protocols 5.4 (2010).
Source
scival
Published In
Cold Spring Harbor Protocols
Volume
5
Issue
4
Publish Date
2010
DOI
10.1101/pdb.prot5416

Photothermal therapy of glioma in a mouse model with near-infrared excited nanoshells

Authors
Day, ES; Zhang, L; Lewinski, NA; Thompson, PA; Drezek, RA; Blaney, SM; West, JL
MLA Citation
Day, ES, Zhang, L, Lewinski, NA, Thompson, PA, Drezek, RA, Blaney, SM, and West, JL. "Photothermal therapy of glioma in a mouse model with near-infrared excited nanoshells." Proceedings of the ASME 1st Global Congress on NanoEngineering for Medicine and Biology 2010, NEMB2010 (2010): 219-220.
Source
scival
Published In
Proceedings of the ASME 1st Global Congress on NanoEngineering for Medicine and Biology 2010, NEMB2010
Publish Date
2010
Start Page
219
End Page
220

Multifaceted nano-and micropatterned surfaces for cell adhesion manipulation

Authors
Slater, JH; Miller, JS; Yu, SS; West, JL
MLA Citation
Slater, JH, Miller, JS, Yu, SS, and West, JL. "Multifaceted nano-and micropatterned surfaces for cell adhesion manipulation." Proceedings of the ASME 1st Global Congress on NanoEngineering for Medicine and Biology 2010, NEMB2010 (2010): 345-346.
Source
scival
Published In
Proceedings of the ASME 1st Global Congress on NanoEngineering for Medicine and Biology 2010, NEMB2010
Publish Date
2010
Start Page
345
End Page
346

Cancer imaging and thermal therapy facilitated by nanoparticles and multiphoton microscopy

Authors
Day, ES; Bickford, LR; Drezek, RA; West, JL
MLA Citation
Day, ES, Bickford, LR, Drezek, RA, and West, JL. "Cancer imaging and thermal therapy facilitated by nanoparticles and multiphoton microscopy." Proceedings of the ASME 1st Global Congress on NanoEngineering for Medicine and Biology 2010, NEMB2010 (2010): 221-222.
Source
scival
Published In
Proceedings of the ASME 1st Global Congress on NanoEngineering for Medicine and Biology 2010, NEMB2010
Publish Date
2010
Start Page
221
End Page
222

Nanoshells for photothermal cancer therapy.

Cancer is a leading cause of death in the United States and contributes to yearly rising health care costs. Current methods of treating cancer involve surgical removal of easily accessible tumors, radiation therapy, and chemotherapy. These methods do not always result in full treatment of the cancer and can in many cases damage healthy cells both surrounding the tissue area and systemically. Nanoshells are optically tunable core/shell nanoparticles that can be fabricated to strongly absorb in the near-infrared (NIR) region where light transmits deeply into tissue. When injected systemically, these particles have been shown to accumulate in the tumor due to the enhanced permeability and retention (EPR) effect and induce photothermal ablation of the tumor when irradiated with an NIR laser. Tumor specificity can be increased via functionalizing the nanoshell surface with tumor-targeting moieties. Nanoshells can also be made to strongly scatter light and therefore can be used in various imaging modalities such as dark-field microscopy and optical coherence tomography (OCT).

Authors
Morton, JG; Day, ES; Halas, NJ; West, JL
MLA Citation
Morton, JG, Day, ES, Halas, NJ, and West, JL. "Nanoshells for photothermal cancer therapy." Methods in molecular biology (Clifton, N.J.) 624 (2010): 101-117.
PMID
20217591
Source
scival
Published In
Methods in molecular biology (Clifton, N.J.)
Volume
624
Publish Date
2010
Start Page
101
End Page
117
DOI
10.1007/978-1-60761-609-2_7

Diagnostic and Therapeutic Applications of Nanotechnology.

Authors
West, JL
MLA Citation
West, JL. "Diagnostic and Therapeutic Applications of Nanotechnology." CANCER RESEARCH 69.24 (December 2009): 484S-484S. (Academic Article)
Source
manual
Published In
Cancer Research
Volume
69
Issue
24
Publish Date
2009
Start Page
484S
End Page
484S

Micropatterning of poly(ethylene glycol) diacrylate hydrogels with biomolecules to regulate and guide endothelial morphogenesis

Angiogenesis, which is morphogenesis undertaken by endothelial cells (ECs) during new blood vessel formation, has been traditionally studied on natural extracellular matrix proteins. In this work, we aimed to regulate and guide angiogenesis on synthetic, bioactive poly(ethylene glycol)-diacrylate (PEGDA) hydrogels. PEGDA hydrogel is intrinsically cell nonadhesive and highly resistant to protein adsorption, allowing a high degree of control over presentation of ligands for cell adhesion and signaling. Since these materials are photopolymerizable, a variety of photolithographic technologies may be applied to spatially control presentation of bioactive ligands. To manipulate EC adhesion, migration, and tubulogenesis, the surface of PEGDA hydrogels was micropatterned with a cell adhesive ligand, Arg-Gly-Asp-Ser (RGDS), in desired concentrations and geometries. ECs cultured on these RGDS patterns reorganized their cell bodies into cord-like structures on 50-μm-wide stripes, but not on wider stripes, suggesting that EC morphogenesis can be regulated by geometrical cues. The cords formed by ECs were reminiscent of capillaries with cells participating in the self-assembly and reorganization into multicellular structures. Further, endothelial cord formation was stimulated on intermediate concentration of RGDS at 20 μg/cm2, whereas it was inhibited at higher concentrations. This work has shown that angiogenic responses can be tightly regulated and guided by micropatterning of bioactive ligands and also demonstrated great potentials of micropatterned PEGDA hydrogels for various applications in tissue engineering, where vascularization prior to implantation is critical. © Copyright 2009, Mary Ann Liebert, Inc. 2009.

Authors
Moon, JJ; Hahn, MS; Kim, I; Nsiah, BA; West, JL
MLA Citation
Moon, JJ, Hahn, MS, Kim, I, Nsiah, BA, and West, JL. "Micropatterning of poly(ethylene glycol) diacrylate hydrogels with biomolecules to regulate and guide endothelial morphogenesis." Tissue Engineering - Part A 15.3 (2009): 579-585.
PMID
18803481
Source
scival
Published In
Tissue Engineering, Part A
Volume
15
Issue
3
Publish Date
2009
Start Page
579
End Page
585
DOI
10.1089/ten.tea.2008.0196

Covalently-immobilized vascular endothelial growth factor promotes endothelial cell tubulogenesis in poly(ethylene glycol) diacrylate hydrogels

The development and use of functional tissue-engineered products is currently limited by the challenge of incorporating microvasculature. To this end, we have investigated strategies to facilitate vascularization in scaffold materials, in this case poly(ethylene glycol) (PEG) hydrogels. These hydrogels are hydrophilic and resist protein adsorption and subsequent non-specific cell adhesion, but can be modified to contain cell-adhesive ligands and growth factors to support cell and tissue function. Additionally, the hydrogel matrix can include proteolytically degradable peptide sequences in the backbone of the structure to allow cells to control scaffold biodegradation, allowing three-dimensional migration. Vascular endothelial growth factor (VEGF), a potent angiogenic signal, and the cell-adhesive peptide RGDS were each covalently attached to PEG monoacrylate linkers. PEGylated RGDS and VEGF were then covalently immobilized in PEG-diacrylate (PEGDA) hydrogels in 2D and 3D. Immobilized VEGF increased endothelial cell tubulogenesis on the surface of non-degradable PEGDA hydrogels 4-fold compared to controls without the growth factor. Endothelial cell behavior in 3D collagenase-degradable hydrogels modified with RGDS and VEGF was observed using time-lapse confocal microscopy. Bulk immobilization of VEGF in 3D collagenase-degradable RGDS-modified hydrogels increased endothelial cell motility 14-fold and cell-cell connections 3-fold. Covalent incorporation of PEGylated VEGF in PEG hydrogels can be a useful tool to promote endothelial cell migration, cell-cell contact formation and tubulogenesis in an effort to produce vascularized tissue-engineered constructs. © 2009 Koninklijke Brill NV, Leiden.

Authors
Leslie-Barbick, JE; Moon, JJ; West, JL
MLA Citation
Leslie-Barbick, JE, Moon, JJ, and West, JL. "Covalently-immobilized vascular endothelial growth factor promotes endothelial cell tubulogenesis in poly(ethylene glycol) diacrylate hydrogels." Journal of Biomaterials Science, Polymer Edition 20.12 (2009): 1763-1779.
PMID
19723440
Source
scival
Published In
Journal of Biomaterials Science, Polymer Edition
Volume
20
Issue
12
Publish Date
2009
Start Page
1763
End Page
1779
DOI
10.1163/156856208X386381

The stabilization and targeting of surfactant-synthesized gold nanorods

The strong cetyltrimethylammonium bromide (CTAB) surfactant responsible for the synthesis and stability of gold nanorod solutions complicates their biomedical applications. The critical parameter to maintain nanorod stability is the ratio of CTAB to nanorod concentration. The ratio is approximately 740 000 as determined by chloroform extraction of the CTAB from a nanorod solution. A comparison of nanorod stabilization by thiol-terminal PEG and by anionic polymers reveals that PEGylation results in higher yields and less aggregation upon removal of CTAB. A heterobifunctional PEG yields nanorods with exposed carboxyl groups for covalent conjugation to antibodies with the zero-length carbodiimide linker EDC. This conjugation strategy leads to approximately two functional antibodies per nanorod according to fluorimetry and ELISA assays. The nanorods specifically targeted cells in vitro and were visible with both two-photon and confocal reflectance microscopies. This covalent strategy should be generally applicable to other biomedical applications of gold nanorods as well as other gold nanoparticles synthesized with CTAB. © 2009 IOP Publishing Ltd.

Authors
Rostro-Kohanloo, BC; Bickford, LR; Payne, CM; Day, ES; Anderson, LJE; Zhong, M; Lee, S; Mayer, KM; Zal, T; Adam, L; Dinney, CPN; Drezek, RA; West, JL; Hafner, JH
MLA Citation
Rostro-Kohanloo, BC, Bickford, LR, Payne, CM, Day, ES, Anderson, LJE, Zhong, M, Lee, S, Mayer, KM, Zal, T, Adam, L, Dinney, CPN, Drezek, RA, West, JL, and Hafner, JH. "The stabilization and targeting of surfactant-synthesized gold nanorods." Nanotechnology 20.43 (2009).
PMID
19801751
Source
scival
Published In
Nanotechnology
Volume
20
Issue
43
Publish Date
2009
DOI
10.1088/0957-4484/20/43/434005

The Flk1-myr::mCherry mouse as a useful reporter to characterize multiple aspects of ocular blood vessel development and disease

The highly vascularized mouse eye is an excellent model system in which to elucidate the molecular genetic basis of blood vessel development and disease. However, the analysis of ocular vessel defects has traditionally been derived from fixed tissue, which fails to account for dynamic events such as blood flow and cell migration. To overcome the limitations of static analysis, tremendous advances in imaging technology and fluorescent protein reporter mouse lines now enable the direct visualization of developing cells in vivo. Here, we demonstrate that the Flk1-myr::mCherry transgenic mouse is an extremely useful live reporter with broad applicability to retinal, hyaloid, and choroid vascular research. © 2009 Wiley-Liss, Inc.

Authors
Poché, RA; Larina, IV; Scott, ML; Saik, JE; West, JL; Dickinson, ME
MLA Citation
Poché, RA, Larina, IV, Scott, ML, Saik, JE, West, JL, and Dickinson, ME. "The Flk1-myr::mCherry mouse as a useful reporter to characterize multiple aspects of ocular blood vessel development and disease." Developmental Dynamics 238.9 (2009): 2318-2326.
PMID
19253403
Source
scival
Published In
Developmental Dynamics
Volume
238
Issue
9
Publish Date
2009
Start Page
2318
End Page
2326
DOI
10.1002/dvdy.21886

Nanoparticles for thermal cancer therapy

Advances in nanotechnology are enabling many new diagnostic and therapeutic approaches in cancer. In this review, examples where nanoparticles are employed to induce localized heating within tumors are explored. Approaches to nanoparticle-mediated thermal therapy include absorption of infrared light, radio frequency ablation, and magnetically-induced heating. These approaches have demonstrated high efficacy in animal models, and two are already in human clinical trials. Copyright © 2009 by ASME.

Authors
Day, ES; Morton, JG; West, JL
MLA Citation
Day, ES, Morton, JG, and West, JL. "Nanoparticles for thermal cancer therapy." Journal of Biomechanical Engineering 131.7 (2009).
PMID
19640133
Source
scival
Published In
Journal of Biomechanical Engineering
Volume
131
Issue
7
Publish Date
2009
DOI
10.1115/1.3156800

Near infrared absorbing nanoparticles for photothermal cancer therapy

Authors
West, JL
MLA Citation
West, JL. "Near infrared absorbing nanoparticles for photothermal cancer therapy." Proceedings of the ASME Summer Bioengineering Conference, SBC2008 PART B (2009): 749-750.
Source
scival
Published In
Proceedings of the ASME Summer Bioengineering Conference, SBC2008
Issue
PART B
Publish Date
2009
Start Page
749
End Page
750

Rapid prototyping of hydrogels to guide tissue formation

The high biocompatibility of hydrogels, their tunable biochemical and mechanical properties, and the myriad methods available for patterning their structure in both two and three dimensions make hydrogels an excellent family of materials for investigating fundamental mechanisms of cell biology and engineering the cellular microenvironment. Ultimately, the vascularization of hydrogels through three-dimensional rapid prototyping and three-dimensional biochemical patterning at subcellular resolution will enable the investigation of small tissue mimics and continue progress toward true synthetic tissues and organs for human transplantation. © Springer 2008.

Authors
Miller, JS; West, JL
MLA Citation
Miller, JS, and West, JL. "Rapid prototyping of hydrogels to guide tissue formation." (December 1, 2008): 49-65. (Chapter)
Source
scopus
Publish Date
2008
Start Page
49
End Page
65
DOI
10.1007/978-0-387-47683-4_4

Thermo-responsive systems for controlled drug delivery

Controlled drug delivery systems represent advanced systems that can be tightly modulated by stimuli in order to treat diseases in which sustained drug release is undesirable. Among the many different stimuli-sensitive delivery systems, temperature-sensitive drug delivery systems offer great potential over their counterparts due to their versatility in design, tunability of phase transition temperatures, passive targeting ability and in situ phase transitions. Thus, thermosensitive drug delivery systems can overcome many of the hurdles of conventional drug delivery systems in order to increase drug efficacies, drug targeting and decrease drug toxicities. in an effort to further control existing temperature-responsive systems, current innovative applications have combined temperature with other stimuli such as pH and light. The result has been the development of highly sophisticated systems, which demonstrate exquisite control over drug release and represent huge advances in biomedical research.

Authors
Bikram, M; West, JL
MLA Citation
Bikram, M, and West, JL. "Thermo-responsive systems for controlled drug delivery." EXPERT OPINION ON DRUG DELIVERY 5.10 (October 2008): 1077-1091. (Academic Article)
PMID
18817514
Source
manual
Published In
Expert Opinion on Drug Delivery
Volume
5
Issue
10
Publish Date
2008
Start Page
1077
End Page
1091
DOI
10.1517/17425240802379846

PMSE 404-Biomimetic strategies in vascular tissue engineering

Authors
West Jennifer, L
MLA Citation
West Jennifer, L. "PMSE 404-Biomimetic strategies in vascular tissue engineering." ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 235 (April 2008). (Academic Article)
Source
manual
Published In
ACS National Meeting Book of Abstracts
Volume
235
Publish Date
2008

Nanotechnology for tissue engineering

© 2008 by Imperial College Press. Future advances in tissue engineering are likely to require new tools and materials that provide novel capabilities for the construction of engineered tissue as well as the analysis and monitoring of such products. Nanotechnology research is yielding many new materials with unprecedented control over structure and function, often with highly unique properties. An example of nanotechnology in tissue engineering are nanoparticles, including quantum dots, where control over the size of semiconductor nanocrystals determines the emission spectra from these highly stable fluorescent probes, carbon nanotubes, which offer the potential to make very strong nanocomposites, and polymeric dendrimers, where the highly branched nature of the material offer opportunity to generate multi-functional particles. Nanotechnology also has advanced nanoscale control over material assembly. In this chapter, we will explore some of the ways that these technologies are being used to improve tissue engineering scaffolds, enhance cellular imaging capabilities, and enable monitoring of biological environments and processes.

Authors
Stephens-Altus, JS; West, JL
MLA Citation
Stephens-Altus, JS, and West, JL. "Nanotechnology for tissue engineering." Advances in Tissue Engineering. January 1, 2008. 333-347.
Source
scopus
Publish Date
2008
Start Page
333
End Page
347
DOI
10.1142/9781848161832_0016

Histogenesis in Three-Dimensional Scaffolds

Authors
Bergman, NM; West, JL
MLA Citation
Bergman, NM, and West, JL. "Histogenesis in Three-Dimensional Scaffolds." Principles of Regenerative Medicine (2008): 686-703.
Source
scival
Published In
Principles of Regenerative Medicine
Publish Date
2008
Start Page
686
End Page
703
DOI
10.1016/B978-012369410-2.50041-3

Ephrin A1-targeted nanoshells for photothermal ablation of prostate cancer cells

Gold-coated silica nanoshells are a class of nanoparticles that can be designed to possess strong absorption of light in the near infrared (NIR) wavelength region. When injected intravenously, these nanoshells have been shown to accumulate in tumors and subsequently mediate photothermal treatment, leading to tumor regression. In this work, we sought to improve their specificity by targeting them. to prostate tumor cells. We report selective targeting of PC-3 cells with nanoshells conjugated to ephrinA1, a ligand for EphA2 receptor that is overexpressed on PC-3 cells. We demonstrate selective photo-thermal destruction of these cells upon application of the NIR laser. © 2008 Gobin et al, publisher and licensee Dove Medical Press Ltd.

Authors
Gobin, AM; Moon, JJ; West, JL
MLA Citation
Gobin, AM, Moon, JJ, and West, JL. "Ephrin A1-targeted nanoshells for photothermal ablation of prostate cancer cells." International Journal of Nanomedicine 3.3 (2008): 351-358.
PMID
18990944
Source
scival
Published In
International journal of nanomedicine
Volume
3
Issue
3
Publish Date
2008
Start Page
351
End Page
358

Immunonanoshells for targeted photothermal ablation in medulloblastoma and glioma: An in vitro evaluation using human cell lines

We are developing a novel approach to specifically target malignant brain tumor cells for photothermal ablation using antibody-tagged, near infrared-absorbing gold-silica nanoshells, referred to as immunonanoshells. Once localized to tumor cells, these nanoshells are extremely efficient at absorbing near-infrared light and can generate sufficient heat to kill cancer cells upon exposure to laser light. In this study, we evaluated the efficacy of immunonanoshells in vitro against both medulloblastoma and high-grade glioma cell lines. We used an antibody against HER2 to target gold-silica nanoshells to medulloblastoma cells, since HER2 is frequently overexpressed in medulloblastoma. We show that treatment with HER2-targeted nanoshells, but not non-targeted nanoshells, followed by exposure to laser light, can induce cell death in the HER2-overexpressing medulloblastoma cell line Daoy.2, as well as the parental Daoy cell line, which expresses HER2 at a moderate level, but not in dermal fibroblasts that do not express HER2. In an analogous set of experiments, we conjugated gold-silica nanoshells to an antibody against interleukin-13 receptor-alpha 2 (IL13Rα2), an antigen that is frequently overexpressed in gliomas. We demonstrate that these immunonanoshells are capable of inducing cell death in two high-grade glioma cell lines that express IL13Rα2, U373 and U87, but not in A431 epidermoid carcinoma cells that do not express significant levels of IL13Rα2. We believe that the use of antibody-tagged gold-silica nanoshells to selectively target cancer cells presents a promising new strategy for the treatment of central nervous system tumors that will minimize the damage and resulting toxicity to the surrounding normal brain. © Springer Science+Business Media, LLC 2007.

Authors
Bernardi, RJ; Lowery, AR; Thompson, PA; Blaney, SM; West, JL
MLA Citation
Bernardi, RJ, Lowery, AR, Thompson, PA, Blaney, SM, and West, JL. "Immunonanoshells for targeted photothermal ablation in medulloblastoma and glioma: An in vitro evaluation using human cell lines." Journal of Neuro-Oncology 86.2 (2008): 165-172.
PMID
17805488
Source
scival
Published In
Journal of Neuro-Oncology
Volume
86
Issue
2
Publish Date
2008
Start Page
165
End Page
172
DOI
10.1007/s11060-007-9467-3

Nitric oxide-releasing polyurethane-PEG copolymer containing the YIGSR peptide promotes endothelialization with decreased platelet adhesion

Thrombosis and intimai hyperplasia are the principal causes of small-diameter vascular graft failure. To improve the long-term patency of polyurethane vascular grafts, we have incorporated both poly(ethylene glycol) and a diazeniumdiolate nitric oxide (NO) donor into the backbone of polyurethane to improve thromboresistance. Additionally, we have incorporated the laminin-derived cell adhesive peptide sequence YIGSR to encourage endothelial cell adhesion and migration, while NO release encourages endothelial cell proliferation. NO production by polyurethane films under physiological conditions demonstrated biphasic release, in which an initial burst of 70% of the incorporated NO was released within 2 days, followed by sustained release over 2 months. Endothelial cell proliferation in the presence of the NO-releasing material was increased as compared to control polyurethane, and platelet adhesion to polyethylene glycol-containing polyurethane was decreased significantly with the addition of the NO donor. © 2007 Wiley Periodicals, Inc.

Authors
Taite, LJ; Yang, P; Jun, H-W; West, JL
MLA Citation
Taite, LJ, Yang, P, Jun, H-W, and West, JL. "Nitric oxide-releasing polyurethane-PEG copolymer containing the YIGSR peptide promotes endothelialization with decreased platelet adhesion." Journal of Biomedical Materials Research - Part B Applied Biomaterials 84.1 (2008): 108-116.
PMID
17497680
Source
scival
Published In
Journal of Biomedical Materials Research Part B: Applied Biomaterials
Volume
84
Issue
1
Publish Date
2008
Start Page
108
End Page
116
DOI
10.1002/jbm.b.30850

Vascularization of engineered tissues: Approaches to promote angiogenesis in biomaterials

Although there have been extensive research efforts to create functional tissues and organs, most successes in tissue engineering have been limited to avascular or thin tissues. The major hurdle in development of more complex tissues lies in the formation of vascular networks capable of delivering oxygen and nutrients throughout the engineered constructs. Sufficient neovascularization in scaffold materials can be achieved through coordinated application of angiogenic factors with proper cell types in biomaterials. This review present the current research developments in the design of biomaterials and their biochemical and biochemical modifications to produce vascularized tissue constructs. © 2008 Bentham Science Publishers Ltd.

Authors
Moon, JJ; West, JL
MLA Citation
Moon, JJ, and West, JL. "Vascularization of engineered tissues: Approaches to promote angiogenesis in biomaterials." Current Topics in Medicinal Chemistry 8.4 (2008): 300-310.
PMID
18393893
Source
scival
Published In
Current Topics in Medicinal Chemistry
Volume
8
Issue
4
Publish Date
2008
Start Page
300
End Page
310
DOI
10.2174/156802608783790983

Blood vessel matrix: A new alternative for abdominal wall reconstruction

Background: Biologic matrices offer a new approach to the management of abdominal wall defects when the use of other foreign material is not ideal. A member of our team (GEA) developed a biological decellularized matrix generated from harvested blood vessels of swine blood vessel matrix (BVMx). The aim of our study was to investigate whether this novel collagen-based biological matrix is safe and effective for the repair of abdominal wall hernia defects in a rat model. Methods: Full thickness abdominal wall defects were created in rats and repaired with our BVMx. After implantation as an underlay for 30 and 90 days, animals were sacrificed and the implanted material evaluated for herniation, adhesions, breaking strength, inflammation, and revascularization. Results: No evidence of herniation was noted at 30 (n = 7) or 90 (n = 7) days after repair. Adhesions, if present, were filmy and easily separated. The mean area of visceral adhesions to the BVMx was 18.9 ± 11.0% at 30 days and 7.1 ± 3.1% at 90 days post implantation (P = 0.33). The breaking strength of the BVMx-fascial interface was 4.5 ± 0.8 N at 30 days and 4.5 ± 2.4 N at 90 days post implantation (P = 0.98). Histologic analysis demonstrated that the BVMx elicited a mild transient inflammatory response and supported fibroblast migration, deposition of newly formed collagen, and neovascularization. Conclusions: These data confirm that this BVMx supports vascular ingrowth and provides adequate strength for the repair of abdominal wall defects. Future studies in a large animal model are required to assess its validity for human application. © Springer-Verlag 2008.

Authors
Bellows, CF; Jian, W; McHale, MK; Cardenas, D; West, JL; Lerner, SP; Amiel, GE
MLA Citation
Bellows, CF, Jian, W, McHale, MK, Cardenas, D, West, JL, Lerner, SP, and Amiel, GE. "Blood vessel matrix: A new alternative for abdominal wall reconstruction." Hernia 12.4 (2008): 351-358.
PMID
18235999
Source
scival
Published In
Hernia
Volume
12
Issue
4
Publish Date
2008
Start Page
351
End Page
358
DOI
10.1007/s10029-008-0340-x

Three-dimensional micropatterning of bioactive hydrogels via two-photon laser scanning photolithography for guided 3D cell migration

Micropatterning techniques that control three-dimensional (3D) arrangement of biomolecules and cells at the microscale will allow development of clinically relevant tissues composed of multiple cell types in complex architecture. Although there have been significant developments to regulate spatial and temporal distribution of biomolecules in various materials, most micropatterning techniques are applicable only to two-dimensional patterning. We report here the use of two-photon laser scanning (TPLS) photolithographic technique to micropattern cell adhesive ligand (RGDS) in hydrogels to guide cell migration along pre-defined 3D pathways. The TPLS photolithographic technique regulates photo-reactive processes in microscale focal volumes to generate complex, free from microscale patterns with control over spatial presentation and concentration of biomolecules within hydrogel scaffolds. The TPLS photolithographic technique was used to dictate the precise location of RGDS in collagenase-sensitive poly(ethylene glycol-co-peptide) diacrylate hydrogels, and the amount of immobilized RGDS was evaluated using fluorescein-tagged RGDS. When human dermal fibroblasts cultured in fibrin clusters were encapsulated within the micropatterned collagenase-sensitive hydrogels, the cells underwent guided 3D migration only into the RGDS-patterned regions of the hydrogels. These results demonstrate the prospect of guiding tissue regeneration at the microscale in 3D scaffolds by providing appropriate bioactive cues in highly defined geometries. © 2008 Elsevier Ltd. All rights reserved.

Authors
Lee, S-H; Moon, JJ; West, JL
MLA Citation
Lee, S-H, Moon, JJ, and West, JL. "Three-dimensional micropatterning of bioactive hydrogels via two-photon laser scanning photolithography for guided 3D cell migration." Biomaterials 29.20 (2008): 2962-2968.
PMID
18433863
Source
scival
Published In
Biomaterials
Volume
29
Issue
20
Publish Date
2008
Start Page
2962
End Page
2968
DOI
10.1016/j.biomaterials.2008.04.004

Thermo-responsive systems for controlled drug delivery

Controlled drug delivery systems represent advanced systems that can be tightly modulated by stimuli in order to treat diseases in which sustained drug release is undesirable. Among the many different stimuli-sensitive delivery systems, temperature-sensitive drug delivery systems offer great potential over their counterparts due to their versatility in design, tunability of phase transition temperatures, passive targeting ability and in situ phase transitions. Thus, thermosensitive drug delivery systems can overcome many of the hurdles of conventional drug delivery systems in order to increase drug efficacies, drug targeting and decrease drug toxicities. In an effort to further control existing temperature-responsive systems, current innovative applications have combined temperature with other stimuli such as pH and light. The result has been the development of highly sophisticated systems, which demonstrate exquisite control over drug release and represent huge advances in biomedical research. © 2008 Informa UK Ltd.

Authors
Bikram, M; West, JL
MLA Citation
Bikram, M, and West, JL. "Thermo-responsive systems for controlled drug delivery." Expert Opinion on Drug Delivery 5.10 (2008): 1077-1091.
Source
scival
Published In
Expert Opinion on Drug Delivery
Volume
5
Issue
10
Publish Date
2008
Start Page
1077
End Page
1091
DOI
10.1517/17425247.5.10.1077

PEGDA hydrogels with patterned rigidity for manipulating cell behavior

PEGDA hydrogels with patterned and gradient elasticity are attractive substrates for the study of cell response to substrate rigidity. Using PEGDA hydrogels with tailored mechanical profiles, we are able to show differences in SMC behavior with substrate elasticity within a single sample. These substrates allow for the investigation of edge effects between substrates of different elasticity, effects of anisotropy on cellular behavior, screening of the effects of a wide range of substrate elasticity on cellular behavior, and investigation of cellular migration in response to a gradient of elasticity.

Authors
Nemir, S; McHale, MK; West, JL
MLA Citation
Nemir, S, McHale, MK, and West, JL. "PEGDA hydrogels with patterned rigidity for manipulating cell behavior." 8th World Biomaterials Congress 2008 2 (2008): 894--.
Source
scival
Published In
8th World Biomaterials Congress 2008
Volume
2
Publish Date
2008
Start Page
894-

Bifurcated microchannel networks in polyethylene glycol (PEG) hydrogels

Authors
Cuchiara, MP; Miller, JS; West, JL
MLA Citation
Cuchiara, MP, Miller, JS, and West, JL. "Bifurcated microchannel networks in polyethylene glycol (PEG) hydrogels." 8th World Biomaterials Congress 2008 3 (2008): 1348--.
Source
scival
Published In
8th World Biomaterials Congress 2008
Volume
3
Publish Date
2008
Start Page
1348-

Bioactive polyurethanes as stent coatings to reduce thombosis

Authors
Bergmann, N; Restrepo, J; West, JL
MLA Citation
Bergmann, N, Restrepo, J, and West, JL. "Bioactive polyurethanes as stent coatings to reduce thombosis." 8th World Biomaterials Congress 2008 4 (2008): 2109--.
Source
scival
Published In
8th World Biomaterials Congress 2008
Volume
4
Publish Date
2008
Start Page
2109-

Endothelial cell tubulogenesis responds to mechanical properties of PEGDA hydrogels with surface immobilized vascular endothelial growth factor

Authors
Leslie, JE; West, JL
MLA Citation
Leslie, JE, and West, JL. "Endothelial cell tubulogenesis responds to mechanical properties of PEGDA hydrogels with surface immobilized vascular endothelial growth factor." 8th World Biomaterials Congress 2008 3 (2008): 1658--.
Source
scival
Published In
8th World Biomaterials Congress 2008
Volume
3
Publish Date
2008
Start Page
1658-

Directed cell spreading and migration with protein gradients in micron-scale ellipses

Authors
Miller, JS; Yu, SS; West, JL
MLA Citation
Miller, JS, Yu, SS, and West, JL. "Directed cell spreading and migration with protein gradients in micron-scale ellipses." 8th World Biomaterials Congress 2008 4 (2008): 1788--.
Source
scival
Published In
8th World Biomaterials Congress 2008
Volume
4
Publish Date
2008
Start Page
1788-

Enhancement of cancer therapy through targeted delivery of nanoshells

Authors
Day, ES; Gobin, AM; Lowery, AR; West, JL
MLA Citation
Day, ES, Gobin, AM, Lowery, AR, and West, JL. "Enhancement of cancer therapy through targeted delivery of nanoshells." 8th World Biomaterials Congress 2008 3 (2008): 1387--.
Source
scival
Published In
8th World Biomaterials Congress 2008
Volume
3
Publish Date
2008
Start Page
1387-

Regulation of endothelial angiogenesis and vasculogenesis in synthetic poly(ethylene glycol) hydrogels modified with biomolecules

Authors
Moon, JJ; Lee, S-H; Hahn, MS; Nsiah, BA; West, JL
MLA Citation
Moon, JJ, Lee, S-H, Hahn, MS, Nsiah, BA, and West, JL. "Regulation of endothelial angiogenesis and vasculogenesis in synthetic poly(ethylene glycol) hydrogels modified with biomolecules." FASEB JOURNAL 21.6 (April 2007): A748-A749. (Academic Article)
Source
manual
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
21
Issue
6
Publish Date
2007
Start Page
A748
End Page
A749

Physiologic pulsatile flow bioreactor conditioning of poly(ethylene glycol)-based tissue engineered vascular grafts.

Mechanical conditioning represents a potential means to enhance the biochemical and biomechanical properties of tissue engineered vascular grafts (TEVGs). A pulsatile flow bioreactor was developed to allow shear and pulsatile stimulation of TEVGs. Physiological 120 mmHg/80 mmHg peak-to-trough pressure waveforms can be produced at both fetal and adult heart rates. Flow rates of 2 mL/sec, representative of flow through small diameter blood vessels, can be generated, resulting in a mean wall shear stress of approximately 6 dynes/cm(2) within the 3 mm ID constructs. When combined with non-thrombogenic poly(ethylene glycol) (PEG)-based hydrogels, which have tunable mechanical properties and tailorable biofunctionality, the bioreactor represents a flexible platform for exploring the impact of controlled biochemical and biomechanical stimuli on vascular graft cells. In the present study, the utility of this combined approach for improving TEVG outcome was investigated by encapsulating 10T-1/2 mouse smooth muscle progenitor cells within PEG-based hydrogels containing an adhesive ligand (RGDS) and a collagenase degradable sequence (LGPA). Constructs subjected to 7 weeks of biomechanical conditioning had significantly higher collagen levels and improved moduli relative to those grown under static conditions.

Authors
Hahn, MS; McHale, MK; Wang, E; Schmedlen, RH; West, JL
MLA Citation
Hahn, MS, McHale, MK, Wang, E, Schmedlen, RH, and West, JL. "Physiologic pulsatile flow bioreactor conditioning of poly(ethylene glycol)-based tissue engineered vascular grafts." Ann Biomed Eng 35.2 (February 2007): 190-200.
PMID
17180465
Source
pubmed
Published In
Annals of Biomedical Engineering
Volume
35
Issue
2
Publish Date
2007
Start Page
190
End Page
200
DOI
10.1007/s10439-006-9099-3

Design and characterization of poly(ethylene glycol) photopolymerizable semi-interpenetrating networks for chondrogenesis of human mesenchymal stem cells

Mesenchymal stem cells (MSCs) are used extensively in cartilage tissue engineering. We have developed a photopolymerizable poly(ethylene glycol diacrylate) (PEGDA) and poly(ethylene glycol) (PEG) semi-interpenetrating network that facilitates the in vitro chondrogenesis of human MSCs (hMSCs). Network parameters were altered and tested for their effects on subsequent matrix elaboration. The mesh size, calculated for each network based on equilibrium swelling ratios, was larger with lower PEGDA:PEG ratios and with higher PEGDA molecular weight. Changes in ξ correlated with changes in extracellular matrix content and deposition in hMSC-seeded networks cultured in vitro for 6 weeks in defined chondrogenic medium. Networks constructed with PEGDA (6 kDa) and PEG (88 kDa) at 1:2 displayed intercellular deposition of proteoglycan. Furthermore, their proteoglycan contents were significantly higher than with PEGDA (6 kDa) hydrogels constructed without the PEG component and those constructed at a PEGDA:PEG ratio of 2:1, which both exhibited pericellular proteoglycan deposition. However, networks constructed with PEGDA (12 and 20 kDa) and PEG (88 kDa) exhibited intercellular deposition of proteoglycan regardless of the ratio employed. Collagen content was lower in networks constructed with PEGDA (12 and 20 kDa) and PEG (88 kDa) at a ratio of 1:2 than in those fabricated at the same PEGDA molecular weights at a ratio of 2:1. This study demonstrated that semi-interpenetrating network parameters influence not only extracellular matrix content, but also the deposition of the matrix molecules by hMSCs undergoing chondrogenesis. It is important that these parameters be considered carefully when creating scaffolds for tissue-engineered cartilage. © 2007 Mary Ann Liebert, Inc.

Authors
Buxton, AN; Zhu, J; Marchant, R; West, JL; Yoo, JU; Johnstone, B
MLA Citation
Buxton, AN, Zhu, J, Marchant, R, West, JL, Yoo, JU, and Johnstone, B. "Design and characterization of poly(ethylene glycol) photopolymerizable semi-interpenetrating networks for chondrogenesis of human mesenchymal stem cells." Tissue Engineering 13.10 (2007): 2549-2560.
PMID
17655489
Source
scival
Published In
Tissue Engineering
Volume
13
Issue
10
Publish Date
2007
Start Page
2549
End Page
2560
DOI
10.1089/ten.2007.0075

Transendothelial migration enhances integrin-dependent human neutrophil chemokinesis

Transendothelial migration of neutrophils induces phenotypic changes that influence the interactions of neutrophils with extravascular tissue components. To assess the influence of transmigration on neutrophil chemokinetic motility, we used polyethylene glycol hydrogels covalently modified with specific peptide sequences relevant to extracellular matrix proteins. We evaluated fMLP-stimulated human neutrophil motility on peptides Arg-Gly-Asp-Ser (RGDS) and TMKIIPFNRTLIGG (P2), alone and in combination. RGDS is a bioactive sequence found in a number of proteins, and P2 is a membrane-activated complex-1 (Mac-1) ligand located in the γ-chain of the fibrinogen protein. We evaluated, via video microscopy, cell motility by measuring cell displacement from origin and total accumulated distance traveled and then calculated average velocity. Results indicate that although adhesion and shape change were supported by hydrogels containing RGD alone, motility was not. Mac-1-dependent motility was supported on hydrogels containing P2 alone. Motility was enhanced through combined presentation of RGD and P2, engaging Mac-1, αVβ 3, and β1 integrins. Naïve neutrophil motility on combined peptide substrates was dependent on Mac-1, and α 4β1 while α6β1 contributed to speed and linear movement. Transmigrated neutrophil motility was dependent on αvβ3 and α5β 1, and α4β1, α 6α1, and Mac-1 contributed to speed and linear motion. Together, the data demonstrate that efficient neutrophil migration, dependent on multi-integrin interaction, is enhanced after transendothelial migration. © Society for Leukocyte Biology.

Authors
Gonzalez, AL; El-Bjeirami, W; West, JL; McIntire, LV; Smith, CW
MLA Citation
Gonzalez, AL, El-Bjeirami, W, West, JL, McIntire, LV, and Smith, CW. "Transendothelial migration enhances integrin-dependent human neutrophil chemokinesis." Journal of Leukocyte Biology 81.3 (2007): 686-695.
PMID
17164427
Source
scival
Published In
Journal of leukocyte biology
Volume
81
Issue
3
Publish Date
2007
Start Page
686
End Page
695
DOI
10.1189/jlb.0906553

Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy

Metal nanoshells are core/shell nanoparticles that can be designed to either strongly absorb or scatter within the near-infrared (NIR) wavelength region (∼650-950 nm). Nanoshells were designed that possess both absorption and scattering properties in the NIR to provide optical contrast for improved diagnostic imaging and, at higher light intensity, rapid heating for photothermal therapy. Using these in a mouse model, we have demonstrated dramatic contrast enhancement for optical coherence tomography (OCT) and effective photothermal ablation of tumors. © 2007 American Chemical Society.

Authors
Gobin, AM; Lee, MH; Halas, NJ; James, WD; Drezek, RA; West, JL
MLA Citation
Gobin, AM, Lee, MH, Halas, NJ, James, WD, Drezek, RA, and West, JL. "Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy." Nano Letters 7.7 (2007): 1929-1934.
PMID
17550297
Source
scival
Published In
Nano Letters
Volume
7
Issue
7
Publish Date
2007
Start Page
1929
End Page
1934
DOI
10.1021/nl070610y

Temperature-sensitive hydrogels with SiO2-Au nanoshells for controlled drug delivery

Silica-gold (SiO2-Au) nanoshells are a new class of nanoparticles that consist of a silica dielectric core that is surrounded by a gold shell. These nanoshells are unique because their peak extinctions are very easily tunable over a wide range of wavelengths particularly in the near infrared (IR) region of the spectrum. Light in this region is transmitted through tissue with relatively little attenuation due to absorption. In addition, irradiation of SiO2-Au nanoshells at their peak extinction coefficient results in the conversion of light to heat energy that produces a local rise in temperature. Thus, to develop a photothermal modulated drug delivery system, we have fabricated nanoshell-composite hydrogels in which SiO2-Au nanoshells of varying concentrations have been embedded within temperature-sensitive hydrogels, for the purpose of initiating a temperature change with light. N-isopropylacrylamide-co-acrylamide (NIPAAm-co-AAm) hydrogels are temperature-sensitive hydrogels that were fabricated to exhibit a lower critical solution temperature (LCST) slightly above body temperature. The resulting composite hydrogels had the extinction spectrum of the SiO2-Au nanoshells in which the hydrogels collapsed reversibly in response to temperature (50 °C) and laser irradiation. The degree of collapse of the hydrogels was controlled by the laser fluence as well as the concentration of SiO2-Au nanoshells. Modulated drug delivery profiles for methylene blue, insulin, and lysozyme were achieved by irradiation of the drug-loaded nanoshell-composite hydrogels, which showed that drug release was dependent upon the molecular weight of the therapeutic molecule. © 2007 Elsevier B.V. All rights reserved.

Authors
Bikram, M; Gobin, AM; Whitmire, RE; West, JL
MLA Citation
Bikram, M, Gobin, AM, Whitmire, RE, and West, JL. "Temperature-sensitive hydrogels with SiO2-Au nanoshells for controlled drug delivery." Journal of Controlled Release 123.3 (2007): 219-227.
PMID
17920154
Source
scival
Published In
Journal of Controlled Release
Volume
123
Issue
3
Publish Date
2007
Start Page
219
End Page
227
DOI
10.1016/j.jconrel.2007.08.013

Synthetic biomimetic hydrogels incorporated with ephrin-A1 for therapeutic angiogenesis

Eph receptor and ephrin ligands are essential for vascular development and angiogenic remodeling. In this work, we developed biomimetic poly(ethylene glycol)-diacrylate hydrogels incorporated with ephrin-A1 and examined their angiogenic properties. Ephrin-A1 was covalently immobilized on the surface of hydrogels by chemical modification and photopolymerization. Ephrin-A1 immobilized on hydrogels was found to retain its capacity to stimulate endothelial cell adhesion in a dose-dependent manner as similar findings were observed on polystyrene culture wells pre-adsorbed with ephrin-A1. Cell adhesion stimulated by ephrin-A1 was abolished by treatment with soluble RGDS and anti-aνβ3 integrin but not anti-aνβ5 integrin antibodies, suggesting that ephrin-A1 activates cell adhesion through aνβ3 integrins. Also, surface immobilized ephrin-A1 was found to induce endothelial tubule formation with luminal diameters ranging 5-30 μ on hydrogels. The results of these studies demonstrate that pro-angiogenic properties of ephrin-A1 are preserved in hydrogels and suggest potential applications of this hydrogel system in regenerative medicine and tissue engineering. © 2007 American Chemical Society.

Authors
Moon, JJ; Lee, S-H; West, JL
MLA Citation
Moon, JJ, Lee, S-H, and West, JL. "Synthetic biomimetic hydrogels incorporated with ephrin-A1 for therapeutic angiogenesis." Biomacromolecules 8.1 (2007): 42-49.
PMID
17206786
Source
scival
Published In
Biomacromolecules
Volume
8
Issue
1
Publish Date
2007
Start Page
42
End Page
49
DOI
10.1021/bm060452p

Endochondral bone formation from hydrogel carriers loaded with BMP2-transduced cells

The success of ex vivo viral gene therapy systems for promoting bone formation could be improved through the development of systems to spatially localize gene expression. Towards this goal, we have encapsulated adenovirus-transduced human diploid fetal lung fibroblasts (MRC-5) expressing bone morphogenetic protein-type 2 (BMP-2) within non-degradable poly(ethylene glycol)-diacrylate (PEG-DA) hydrogels and implanted these intramuscularly to promote endochondral bone formation. To optimize BMP-2 secretion, the molecular weight of the polymers and cell densities were varied. Polymers with molecular weights of 6, 10, and 20 kDa were used to prepare hydrogels containing 1, 5, or 10 million transduced cells. The results showed that 10 million transduced fibroblasts that was the maximum number of cells feasible for encapsulation within PEG-DA 10 and 20 kDa hydrogels produced the highest amount of secreted BMP-2 protein. Encapsulation of MRC-5 and transduced fibroblasts resulted in 71 and 58% cell viability, respectively. The bioactivity of secreted BMP-2 protein from the hydrogels was confirmed with an alkaline phosphatase assay. Micro-CT of the lower limb muscles of NOD/SCID mice following implantation with hydrogels showed 39.5 ± 25.0 mm3 mineralized tissue and 31.8 ± 7.8 mm3 for the cell-injected mice, and the bone was localized to the hydrogel surfaces. Histology revealed bone as well as cartilage for both hydrogel implanted and cell-injected animals. © Biomedical Engineering Society 2007.

Authors
Bikram, M; Fouletier-Dilling, C; Hipp, JA; Gannon, F; Davis, AR; Olmsted-Davis, EA; West, JL
MLA Citation
Bikram, M, Fouletier-Dilling, C, Hipp, JA, Gannon, F, Davis, AR, Olmsted-Davis, EA, and West, JL. "Endochondral bone formation from hydrogel carriers loaded with BMP2-transduced cells." Annals of Biomedical Engineering 35.5 (2007): 796-807.
PMID
17340196
Source
scival
Published In
Annals of Biomedical Engineering
Volume
35
Issue
5
Publish Date
2007
Start Page
796
End Page
807
DOI
10.1007/s10439-007-9263-4

Application of INAA to the build-up and clearance of gold nanoshells in clinical studies in mice

Clinical studies have been carried out for detailed measurements of the build-up and clearance of engineered gold nanoshell in the tissues of dosed mice. These optically tunable nanoshells are under consideration for a new therapy for tumors. The proposed therapy would involve the injection of the nanoshells and their preferential accumulation in tumor sites. This will be followed by irradiation with a monochromatic near infrared laser, which will induce cellular hyperthermia, thereby eradicating the tumor. Neutron activation analysis has been used for the detection and quantitation of gold, and therefore, the nanoshells, in dosing materials, blood, bones and other tissues as well as tumors at varioius sacrifice times following dosing. Feasibility studies have shown instrumental neutron activation analysis to be uniquely suited for detection of the gold nanoshells over a wide dynamic range. This allows for the study of high concentrations of gold in tissues which scavenge the shells from the blood (liver, spleen, kidney) as well as for much lower concentrations in those which do not (muscle, brain). In particular, the tissues from animals sacrificed after the longest post dose delay (28 days) and the control animals required experimental optimization to ensure the lowest possible determination limits. The mass of gold in the tissue samples ranged from our determination limit (about 70 pg) to a few micrograms. © 2007 Akadémiai Kiadó.

Authors
James, WD; Hirsch, LR; West, JL; O'Neal, PD; Payne, JD
MLA Citation
James, WD, Hirsch, LR, West, JL, O'Neal, PD, and Payne, JD. "Application of INAA to the build-up and clearance of gold nanoshells in clinical studies in mice." Journal of Radioanalytical and Nuclear Chemistry 271.2 (2007): 455-459.
Source
scival
Published In
Journal of Radioanalytical and Nuclear Chemistry
Volume
271
Issue
2
Publish Date
2007
Start Page
455
End Page
459
DOI
10.1007/s10967-007-0230-1

Fabrication of 3D hepatic tissues by additive photopatterning of cellular hydrogels

We have fabricated a hepatic tissue construct using a multilayer photopatterning platform for embedding cells in hydrogels of complex architecture. We first explored the potential of established hepatocyte culture models to stabilize isolated hepatocytes for photoencapsulation (e.g., double gel, Matrigel, cocultivation with nonparenchymal cells). Using photopolymerizable PEG hydrogels, we then tailored both the chemistry and architecture of the hydrogels to further support hepatocyte survival and liver-specific function. Specifically, we incorporated adhesive peptides to ligate key integrins on these adhesion-dependent cells. To identify the appropriate peptides for incorporation, the integrin expression of cultured hepatocytes was monitored by flow cytometry and their functional role in cell adhesion was assessed on full-length extracellular matrix (ECM) molecules and their adhesive peptide domains. In addition, we modified the hydrogel architecture to minimize barriers to nutrient transport for these highly metabolic cells. Viability of encapsulated cells was improved in photopatterned hydrogels with structural features of 500 μm in width over unpatterned, bulk hydrogels. Based on these findings, we fabricated a multilayer photopatterned PEG hydrogel structure containing the adhesive RGD peptide sequence to ligate the α5β1 integrin of cocultured hepatocytes. Three-dimensional photopatterned constructs were visualized by digital volumetric imaging and cultured in a continuous flow bioreactor for 12 d where they performed favorably in comparison to unpatterned, unperfused constructs. These studies will have impact in the field of liver biology as well as provide enabling tools for tissue engineering of other organs. © FASEB.

Authors
Tsang, VL; Chen, AA; Cho, LM; Jadin, KD; Sah, RL; DeLong, S; West, JL; Bhatia, SN
MLA Citation
Tsang, VL, Chen, AA, Cho, LM, Jadin, KD, Sah, RL, DeLong, S, West, JL, and Bhatia, SN. "Fabrication of 3D hepatic tissues by additive photopatterning of cellular hydrogels." FASEB Journal 21.3 (2007): 790-801.
PMID
17197384
Source
scival
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
21
Issue
3
Publish Date
2007
Start Page
790
End Page
801
DOI
10.1096/fj.06-7117com

Poly(ethylene glycol) hydrogels conjugated with a collagenase-sensitive fluorogenic substrate to visualize collagenase activity during three-dimensional cell migration

We have developed collagenase-sensitive hydrogels by incorporating a collagenase-sensitive fluorogenic substrate (CS-FS) within the backbone of a polyethylene glycol (PEG) copolymer to visualize collagenase activity during three-dimensional cell migration. CS-FS was synthesized by conjugating Bodipy dyes to a peptide with collagenase-sensitive sequence, Leu-Gly-Pro-Ala (LGPA), and the products were grafted into the collagenase-sensitive PEG hydrogels. CS-FS both in solution and hydrogels had an increase in the fluorescence intensity after proteolytic degradation by collagenase, but not by non-targeted proteases nor in the absence of an enzyme. Fibroblasts inside the hydrogels conjugated with CS-FS spread and extended lamellipodia in three dimensions over several days, and their pericellular collagenase-mediated proteolysis of the hydrogel was visualized via confocal microscopy. A matrix metalloproteinase inhibitor, served as a negative control, significantly reduced the degradation rate of CS-FS by collagenase and prevented cell migration and cell-mediated collagenase activity inside these hydrogels. In summary, we have fabricated collagenase-sensitive hydrogels incorporated with CS-FS and successfully visualized the collagenase activity during three-dimensional cell migration. © 2007 Elsevier Ltd. All rights reserved.

Authors
Lee, S-H; Moon, JJ; Miller, JS; West, JL
MLA Citation
Lee, S-H, Moon, JJ, Miller, JS, and West, JL. "Poly(ethylene glycol) hydrogels conjugated with a collagenase-sensitive fluorogenic substrate to visualize collagenase activity during three-dimensional cell migration." Biomaterials 28.20 (2007): 3163-3170.
PMID
17395258
Source
scival
Published In
Biomaterials
Volume
28
Issue
20
Publish Date
2007
Start Page
3163
End Page
3170
DOI
10.1016/j.biomaterials.2007.03.004

Gold nanoshells aided optical imaging in vitro, in vivo, and ex vivo

Scatter-based optical imaging technologies such as Optical Coherence Tomography (OCT) and Reflectance Confocal Microscopy (RCM) offer a unique non-invasive approach to the detection, diagnosis, and monitoring of cancer. In this article, we describe the use of targeted NIR-tuned gold nanoshell for imaging in vitro, ex vivo and in vivo. Nanoshells are a new class of optically active nanoparticles with tunable plasmon resonances based on geometric construction. These particles can be easily tuned to absorb or scatter strongly within the wavelengths of 650-1300 nm, known as the near infrared region. This region is of significant biological importance providing a therapeutic window and imaging applications in tissue as the primary components of tissue, blood and water, do not have significant absorption coefficients in this range of wavelengths.

Authors
Lee, M; Loo, C; Gobin, AM; Park, J; West, J; Halas, N; Drezek, R
MLA Citation
Lee, M, Loo, C, Gobin, AM, Park, J, West, J, Halas, N, and Drezek, R. "Gold nanoshells aided optical imaging in vitro, in vivo, and ex vivo." 2007 NSTI Nanotechnology Conference and Trade Show - NSTI Nanotech 2007, Technical Proceedings 2 (2007): 306-309.
Source
scival
Published In
2007 NSTI Nanotechnology Conference and Trade Show - NSTI Nanotech 2007, Technical Proceedings
Volume
2
Publish Date
2007
Start Page
306
End Page
309

Gold nanoshells: A multifunctional agent for integrated diagnosis and therapy

Authors
James, WD; Gobin, AM; Lee, MH; Halas, NJ; Drezek, RA; West, JL
MLA Citation
James, WD, Gobin, AM, Lee, MH, Halas, NJ, Drezek, RA, and West, JL. "Gold nanoshells: A multifunctional agent for integrated diagnosis and therapy." Transactions of the American Nuclear Society 97 (2007): 333--.
Source
scival
Published In
Transactions- American Nuclear Society
Volume
97
Publish Date
2007
Start Page
333-

COLL 162-Diagnostic and therapeutic applications of nanotechnology

Authors
West, JL; Drezek, R; Halas, NJ
MLA Citation
West, JL, Drezek, R, and Halas, NJ. "COLL 162-Diagnostic and therapeutic applications of nanotechnology." ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 232 (September 2006). (Academic Article)
Source
manual
Published In
ACS National Meeting Book of Abstracts
Volume
232
Publish Date
2006

HIST 5-Biofunctional biomaterials

Authors
West Jennifer, L
MLA Citation
West Jennifer, L. "HIST 5-Biofunctional biomaterials." ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 232 (September 2006). (Academic Article)
Source
manual
Published In
ACS National Meeting Book of Abstracts
Volume
232
Publish Date
2006

Promotion of endothelial tubulogenesis with EphrinA1 and EphB4 conjugated to synthetic hydrogels

Authors
Moon, JJ; Lee, S; West, JL
MLA Citation
Moon, JJ, Lee, S, and West, JL. "Promotion of endothelial tubulogenesis with EphrinA1 and EphB4 conjugated to synthetic hydrogels." FASEB JOURNAL 20.4 (March 2006): A12-A12. (Academic Article)
Source
manual
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
20
Issue
4
Publish Date
2006
Start Page
A12
End Page
A12

Controlling the cellular response of nanomaterials

Authors
Sayes Christie, M; West Jennifer, L; Colvin Vicki, L
MLA Citation
Sayes Christie, M, West Jennifer, L, and Colvin Vicki, L. "Controlling the cellular response of nanomaterials." ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 231 (March 2006). (Academic Article)
Source
manual
Published In
ACS National Meeting Book of Abstracts
Volume
231
Publish Date
2006

Novel heparanase-inhibiting antibody reduces neointima formation

Basic fibroblast growth factor (bFGF), stored bound to heparan sulfate proteoglycans in the extracellular matrix (ECM) of the arterial media, may initiate smooth muscle cell (SIVIC) proliferation after coronary intervention, thus contributing to restenosis. bFGF mobilization from ECM stores after injury may be induced by platelet degranulation products such as heparanase. Therapies aimed at the inhibition of bFGF release and activation may assist in prevention of restenosis. To test this theory, we first examined the mobilization and activation of bFGF in the arterial media by platelet-derived heparanase. Heparanase, locally delivered to the rat carotid artery, was found to release bFGF and induce substantial SMC proliferation in the absence of actual vascular injury. An antibody that neutralizes heparanase was then developed and evaluated in a rat carotid balloon injury model. Local delivery of anti-heparanase IgG was found to inhibit bFGF release by approximately 60\% (p

Authors
Myler, HA; Lipke, EA; Rice, EE; West, JL
MLA Citation
Myler, HA, Lipke, EA, Rice, EE, and West, JL. "Novel heparanase-inhibiting antibody reduces neointima formation." JOURNAL OF BIOCHEMISTRY 139.3 (March 2006): 339-345. (Academic Article)
Source
manual
Published In
The Journal of Biochemistry
Volume
139
Issue
3
Publish Date
2006
Start Page
339
End Page
345
DOI
10.1093/jb.mvj061

ECM interactions with neutrophil integrins regulate cell activity: An engineering approach to studying cell motility in inflammation

Authors
Gonzalez Simon, AL; West, JL; McIntire, LV; Smith, CW
MLA Citation
Gonzalez Simon, AL, West, JL, McIntire, LV, and Smith, CW. "ECM interactions with neutrophil integrins regulate cell activity: An engineering approach to studying cell motility in inflammation." FASEB JOURNAL 20.5 (March 2006): A1080-A1080. (Academic Article)
Source
manual
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
20
Issue
5
Publish Date
2006
Start Page
A1080
End Page
A1080

Overexpression of lysyl oxidase to increase matrix crosslinking and improve tissue strength in dermal wound healing

In this study, we aimed to increase crosslinking in collagen and elastin in the extracellular matrix through overexpression of lysyl oxidase (LO) in order to improve mechanical strength in dermal wounds during healing. We had used a gene activated matrix (GAM) approach to locally deliver plasmid DNA (pDNA) complexed with polyethylenimine (PEI) in collagen gels at the wound site for localized and sustained transfection of cells involved in the healing process. We first demonstrated in vitro that PEI-pDNA complexes in collagen gels could be taken up and expressed by cultured fibroblasts for at least 20 days. In vitro studies showed that fibroblast-seeded GAMs with the LO transgene exhibited over a 3-fold increase in mechanical strength as compared with a green fluorescent protein (GFP)-transgene control. Addition of an inhibitor of LO abolished this increase. We applied this system in a rat dermal wound healing model and showed that treatment with LO-producing GAMs led to significantly enhanced mechanical strength of the wound site. © 2006 Biomedical Engineering Society.

Authors
Lau, Y-KI; Gobin, AM; West, JL
MLA Citation
Lau, Y-KI, Gobin, AM, and West, JL. "Overexpression of lysyl oxidase to increase matrix crosslinking and improve tissue strength in dermal wound healing." Annals of Biomedical Engineering 34.8 (2006): 1239-1246.
PMID
16804742
Source
scival
Published In
Annals of Biomedical Engineering
Volume
34
Issue
8
Publish Date
2006
Start Page
1239
End Page
1246
DOI
10.1007/s10439-006-9130-8

Bioactive hydrogel substrates: Probing leukocyte receptor-ligand interactions in parallel plate flow chamber studies

The binding of activated integrins on the surface of leukocytes facilitates the adhesion of leukocytes to vascular endothelium during inflammation. Interactions between selectins and their ligands mediate rolling, and are believed to play an important role in leukocyte adhesion, though the minimal recognition motif required for physiologic interactions is not known. We have developed a novel system using poly(ethylene glycol) (PEG) hydrogels modified with either integrin-binding peptide sequences or the selectin ligand sialyl Lewis X (SLeX) within a parallel plate flow chamber to examine the dynamics of leukocyte adhesion to specific ligands. The adhesive peptide sequences arginine-glycine-aspartic acid-serine (RGDS) and leucine-aspartic acid-valine (LDV) as well as sialyl Lewis X were bound to the surface of photopolymerized PEG diacrylate hydrogels. Leukocytes perfused over these gels in a parallel plate flow chamber at physiological shear rates demonstrate both rolling and firm adhesion, depending on the identity and concentration of ligand bound to the hydrogel substrate. This new system provides a unique polymer-based model for the study of interactions between leukocytes and endothelium as well as a platform to develop improved scaffolds for cardiovascular tissue engineering. © Biomedical Engineering Society 2006.

Authors
Taite, LJ; Rowland, ML; Ruffino, KA; Smith, BRE; Lawrence, MB; West, JL
MLA Citation
Taite, LJ, Rowland, ML, Ruffino, KA, Smith, BRE, Lawrence, MB, and West, JL. "Bioactive hydrogel substrates: Probing leukocyte receptor-ligand interactions in parallel plate flow chamber studies." Annals of Biomedical Engineering 34.11 (2006): 1705-1711.
PMID
17031598
Source
scival
Published In
Annals of Biomedical Engineering
Volume
34
Issue
11
Publish Date
2006
Start Page
1705
End Page
1711
DOI
10.1007/s10439-006-9173-x

Angiogenesis-like activity of endothelial cells co-cultured with VEGF-producing smooth muscle cells

A number of strategies have been investigated to improve therapeutic vascularization of ischemic and bioengineered tissues. In these studies, we genetically modified vascular smooth muscle cells (VSMC) to promote endothelial cell proliferation, migration, and formation of microvascular networks. VSMCs were virally transduced to produce vascular endothelial growth factor (VEGF), which acts as a chemoattractant and mitogen of endothelial cells (EC). VSMCs transduced with VEGF165 cDNA produced significant levels of the protein (2-4 ng/105 cell/day). The proliferation of ECs increased after exposure to VEGF-transfected SMCs or their conditioned media. The chemotactic response of ECs to the VEGF-producing cells was explored in two in vitro systems, the modified Boyden chamber assay and a 2-D fence-style migration assay, and both demonstrated increased migration of ECs in response to VEGF-transfected cells. Furthermore, endothelial cells seeded on top of the VEGF-transfected SMCs formed capillary-like structures. These results suggest that VSMCs genetically modified to produce VEGF could be a potential delivery mechanism to enhance endothelial cell migration and subsequent capillary formation, which in turn could improve vascularization of ischemic or regenerating tissue. Furthermore, this system could potentially be used as an in vitro test bed for evaluation of novel angiogenic and anti-angiogenic compounds. © Mary Ann Liebert, Inc.

Authors
Elbjeirami, WM; West, JL
MLA Citation
Elbjeirami, WM, and West, JL. "Angiogenesis-like activity of endothelial cells co-cultured with VEGF-producing smooth muscle cells." Tissue Engineering 12.2 (2006): 381-390.
PMID
16548696
Source
scival
Published In
Tissue Engineering
Volume
12
Issue
2
Publish Date
2006
Start Page
381
End Page
390
DOI
10.1089/ten.2006.12.381

Metal nanoshells

Metal nanoshells are a new class of nanoparticles with highly tunable optical properties. Metal nanoshells consist of a dielectric core nanoparticle such as silica surrounded by an ultrathin metal shell, often composed of gold for biomedical applications. Depending on the size and composition of each layer of the nanoshell, particles can be designed to either absorb or scatter light over much of the visible and infrared regions of the electromagnetic spectrum, including the near infrared region where penetration of light through tissue is maximal. These particles are also effective substrates for surface-enhanced Raman scattering (SERS) and are easily conjugated to antibodies and other biomolecules. One can envision a myriad of potential applications of such tunable particles. Several potential biomedical applications are under development, including immunoassays, modulated drug delivery, photothermal cancer therapy, and imaging contrast agents. © 2006 Biomedical Engineering Society.

Authors
Hirsch, LR; Gobin, AM; Lowery, AR; Tam, F; Drezek, RA; Halas, NJ; West, JL
MLA Citation
Hirsch, LR, Gobin, AM, Lowery, AR, Tam, F, Drezek, RA, Halas, NJ, and West, JL. "Metal nanoshells." Annals of Biomedical Engineering 34.1 (2006): 15-22.
PMID
16528617
Source
scival
Published In
Annals of Biomedical Engineering
Volume
34
Issue
1
Publish Date
2006
Start Page
15
End Page
22
DOI
10.1007/s10439-005-9001-8

Photolithographic patterning of polyethylene glycol hydrogels

A simple, inexpensive photolithographic method for surface patterning deformable, solvated substrates is demonstrated using photoactive poly(ethylene glycol) (PEG)-diacrylate hydrogels as model substrates. Photolithographic masks were prepared by printing the desired patterns onto transparencies using a laser jet printer. Precursor solutions containing monoacryloyl-PEG-peptide and photoinitiator were layered onto hydrogel surfaces. The acrylated moieties in the precursor solution were then conjugated in monolayers to specific hydrogel regions by exposure to UV light through the transparency mask. The effects of UV irradiation time and precursor solution concentration on the levels of immobilized peptide were characterized, demonstrating that bound peptide concentration can be controlled by tuning these parameters. Multiple peptides can be immobilized to a single hydrogel surface in distinct patterns by sequential application of this technique, opening up its potential use in co-cultures. In addition, 3D structures can be generated by incorporating PEG-diacrylate into the precursor solution. To evaluate the feasibility of using these patterned surfaces for guiding cell behavior, human dermal fibroblast adhesion on hydrogel surfaces patterned with acryloyl-PEG-RGDS was investigated. This patterning method may find use in tissue engineering, the elucidation of fundamental structure-function relationships, and the formation of immobilized cell and protein arrays for biotechnology. © 2005 Elsevier Ltd. All rights reserved.

Authors
Hahn, MS; Taite, LJ; Moon, JJ; Rowland, MC; Ruffino, KA; West, JL
MLA Citation
Hahn, MS, Taite, LJ, Moon, JJ, Rowland, MC, Ruffino, KA, and West, JL. "Photolithographic patterning of polyethylene glycol hydrogels." Biomaterials 27.12 (2006): 2519-2524.
PMID
16375965
Source
scival
Published In
Biomaterials
Volume
27
Issue
12
Publish Date
2006
Start Page
2519
End Page
2524
DOI
10.1016/j.biomaterials.2005.11.045

Poly(ethylene glycol)-lysine dendrimers for targeted delivery of nitric oxide

We have synthesized dendrimers of the amino-acid lysine bound to a central poly(ethylene glycol) (PEG) core, and then formed multiple diazeniumdiolate nitric oxide (NO) donors on the lysine residues. NO release from these materials occurred for up to 60 days under physiological conditions. These materials display the ability to regulate vascular cell proliferation and inhibit platelet adhesion to thrombogenic surfaces. When modified with a targeting ligand specific for inflamed endothelium (Sialyl Lewis X), we were able to demonstrate binding of fluorescently-labeled dendrimers to endothelial cells activated by interleukin 1β (IL-1β). © VSP 2006.

Authors
Taite, LJ; West, JL
MLA Citation
Taite, LJ, and West, JL. "Poly(ethylene glycol)-lysine dendrimers for targeted delivery of nitric oxide." Journal of Biomaterials Science, Polymer Edition 17.10 (2006): 1159-1172.
Source
scival
Published In
Journal of Biomaterials Science, Polymer Edition
Volume
17
Issue
10
Publish Date
2006
Start Page
1159
End Page
1172
DOI
10.1163/156856206778530696

Laser-scanning lithography (LSL) for the soft lithographic patterning of cell-adhesive self-assembled monolayers

We report the development of laser-scanning lithography (LSL), which employs a laser-scanning confocal microscope to pattern photoresists that can be utilized, for example, in the fabrication of masters for use in soft lithography. This convenient technique provides even exposure across the entire view field and facilitates accurate alignment of successive photoresist exposures. Features on the scale of 3 μm have been achieved to date with a 10x objective (NA 0.45). Virtual masks, instructions for laser irradiation, were drawn using the Region of Interest (ROI) function of a Zeiss LSM 510 microscope. These regions were then exposed to a 458 nm argon laser for 32 μs (0.9 mW/μm2). Differential interference contrast (DIC) imaging was utilized with a non-destructive 514 nm argon laser as an immediate quality check of each exposure, to align successive exposures, and to reduce chromatic aberration between imaging and exposure. Developed masters were replica-molded with poly(dimethylsiloxane) (PDMS); these masters were then utilized for microcontact printing of cell-adhesive self-assembled monolayers (SAMs) to demonstrate the utility of this process. Initial studies confirmed that human dermal fibroblast adhesion and spreading were limited to cell-adhesive SAM areas. LSL is a rapid, flexible, and readily available technique that will accelerate master design and preparation; moreover, it can be applied to additional forms of photolithography and photopolymerization for studies in cell biology, biomaterials design and evaluation, materials science, and surface chemistry. © 2006 Wiley Periodicals, Inc.

Authors
Miller, JS; Béthencourt, MI; Hahn, M; Lee, TR; West, JL
MLA Citation
Miller, JS, Béthencourt, MI, Hahn, M, Lee, TR, and West, JL. "Laser-scanning lithography (LSL) for the soft lithographic patterning of cell-adhesive self-assembled monolayers." Biotechnology and Bioengineering 93.6 (2006): 1060-1068.
PMID
16444742
Source
scival
Published In
Biotechnology & Bioengineering
Volume
93
Issue
6
Publish Date
2006
Start Page
1060
End Page
1068
DOI
10.1002/bit.20809

Correlating nanoscale titania structure with toxicity: A cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells

Nanocrystalline titanium dioxide (nano-TiO2) is an important material used in commerce today. When designed appropriately it can generate reactive species (RS) quite efficiently, particularly under ultraviolet (UV) illumination; this feature is exploited in applications ranging from self-cleaning glass to low-cost solar cells. In this study, we characterize the toxicity of this important class of nanomaterials under ambient (e.g., no significant light illumination) conditions in cell culture. Only at relatively high concentrations (100 μg/ml) of nanoscale titania did we observe cytotoxicity and inflammation; these cellular responses exhibited classic dose-response behavior, and the effects increased with time of exposure. The extent to which nanoscale titania affected cellular behavior was not dependent on sample surface area in this study; smaller nanoparticlulate materials had effects comparable to larger nanoparticle materials. What did correlate strongly to cytotoxicity, however, was the phase composition of the nanoscale titania. Anatase TiO2, for example, was 100 times more toxic than an equivalent sample of rutile TiO2. The most cytotoxic nanoparticle samples were also the most effective at generating reactive oxygen species; ex vivo RS species generation under UV illumination correlated well with the observed biological response. These data suggest that nano-TiO2 samples optimized for RS production in photocatalysis are also more likely to generate damaging RS species in cell culture. The result highlights the important role that ex vivo measures of RS production can play in developing screens for cytotoxicity. © 2006 Oxford University Press.

Authors
Sayes, CM; Wahi, R; Kurian, PA; Liu, Y; West, JL; Ausman, KD; Warheit, DB; Colvin, VL
MLA Citation
Sayes, CM, Wahi, R, Kurian, PA, Liu, Y, West, JL, Ausman, KD, Warheit, DB, and Colvin, VL. "Correlating nanoscale titania structure with toxicity: A cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells." Toxicological Sciences 92.1 (2006): 174-185.
PMID
16613837
Source
scival
Published In
Toxicological Sciences (Elsevier)
Volume
92
Issue
1
Publish Date
2006
Start Page
174
End Page
185
DOI
10.1093/toxsci/kfj197

Immunonanoshell laser-assisted therapy targets and ablates tumor cells.

Authors
Lowery, AR; Gobin, AM; Day, ES; Halas, NJ; West, JL
MLA Citation
Lowery, AR, Gobin, AM, Day, ES, Halas, NJ, and West, JL. "Immunonanoshell laser-assisted therapy targets and ablates tumor cells." BREAST CANCER RESEARCH AND TREATMENT 100 (2006): S289-S289. (Academic Article)
Source
manual
Published In
Breast Cancer Research and Treatment
Volume
100
Publish Date
2006
Start Page
S289
End Page
S289

Immunonanoshells for targeted photothermal ablation of tumor cells

Consisting of a silica core surrounded by a thin gold shell, nanoshells possess an optical tunability that spans the visible to the near infrared (NIR) region, a region where light penetrates tissues deeply. Conjugated with tumor-specific antibodies, NIR-absorbing immunonanoshells can preferentially bind to tumor cells. NIR light then heats the bound nanoshells, thus destroying the targeted cells. Antibodies can be consistently bound to the nanoshells via a bifunctional polyethylene glycol (PEG) linker at a density of ~150 antibodies per nanoshell. In vitro studies have confirmed the ability to selectively induce cell death with the photothermal interaction of immunonanoshells and NIR light. Prior to incubation with anti-human epidermal growth factor receptor (HER2) immunonanoshells, HER2-expressing SK-BR-3 breast carcinoma cells were seeded alone or adjacent to human dermal fibroblasts (HDFs). Anti-HER2 immunonanoshells bound to HER2-expressing cells resulted in the death of SK-BR-3 cells after NIR exposure only within the irradiated area, while HDFs remained viable after similar treatment since the immunonanoshells did not bind to these cells at high levels. Control nanoshells, conjugated with nonspecific anti-IgG or PEG, did not bind to either cell type, and cells continued to be viable after treatment with these control nanoshells and NIR irradiation. © 2006 Dove Medical Press Limited. All rights reserved.

Authors
Lowery, AR; Gobin, AM; Day, ES; Halas, NJ; West, JL
MLA Citation
Lowery, AR, Gobin, AM, Day, ES, Halas, NJ, and West, JL. "Immunonanoshells for targeted photothermal ablation of tumor cells." International Journal of Nanomedicine 1.2 (2006): 149-154.
PMID
17722530
Source
scival
Published In
International journal of nanomedicine
Volume
1
Issue
2
Publish Date
2006
Start Page
149
End Page
154
DOI
10.2147/nano.2006.1.2.149

Three-dimensional biochemical and biomechanical patterning of hydrogels for guiding cell behavior

A new model for the fabrication of internally complex materials through controlled 3D biochemical and biomechanical patterning of hydrogels and guiding cell behavior within existing photoactive scaffolds is presented. It has been approved using single-photon absorption (SPA) and two-photon absorption (TPA) photolithography to internally immobilize mono- and diacrylate-derivatized moieties into performed poly(ethylene glycol) (PEG)-diacrylate (PEGDA) hydrogels. The pattering can potentially be extended to the creation of complex 3D structures on surfaces rather than within existing networks. The generated internally complex materials through the model can be used to guide cell migration can be used to guide cell migration and represents a significant approach for the exploration of biotechnology.

Authors
Hahn, MS; Miller, JS; West, JL
MLA Citation
Hahn, MS, Miller, JS, and West, JL. "Three-dimensional biochemical and biomechanical patterning of hydrogels for guiding cell behavior." Advanced Materials 18.20 (2006): 2679-2684.
Source
scival
Published In
Advanced Materials
Volume
18
Issue
20
Publish Date
2006
Start Page
2679
End Page
2684
DOI
10.1002/adma.200600647

Functionalization density dependence of single-walled carbon nanotubes cytotoxicity in vitro

The cytotoxic response of cells in culture is dependant on the degree of functionalization of the single-walled carbon nanotube (SWNT). After characterizing a set of water-dispersible SWNTs, we performed in vitro cytotoxicity screens on cultured human dermal fibroblasts (HDF). The SWNT samples used in this exposure include SWNT-phenyl-SO3H and SWNT-phenyl-SO3Na (six samples with carbon/-phenyl-SO3X ratios of 18, 41, and 80), SWNT-phenyl-(COOH)2 (one sample with carbon/-phenyl-(COOH)2 ratio of 23), and underivatized SWNT stabilized in 1% Pluronic F108. We have found that as the degree of sidewall functionalization increases, the SWNT sample becomes less cytotoxic. Further, sidewall functionalized SWNT samples are substantially less cytotoxic than surfactant stabilized SWNTs. Even though cell death did not exceed 50% for cells dosed with sidewall functionalized SWNTs, optical and atomic force microscopies show direct contact between cellular membranes and water-dispersible SWNTs; i.e. the SWNTs in aqueous suspension precipitate out and selectively deposit on the membrane. © 2005 Elsevier Ireland Ltd. All rights reserved.

Authors
Sayes, CM; Liang, F; Hudson, JL; Mendez, J; Guo, W; Beach, JM; Moore, VC; Doyle, CD; West, JL; Billups, WE; Ausman, KD; Colvin, VL
MLA Citation
Sayes, CM, Liang, F, Hudson, JL, Mendez, J, Guo, W, Beach, JM, Moore, VC, Doyle, CD, West, JL, Billups, WE, Ausman, KD, and Colvin, VL. "Functionalization density dependence of single-walled carbon nanotubes cytotoxicity in vitro." Toxicology Letters 161.2 (2006): 135-142.
PMID
16229976
Source
scival
Published In
Toxicology Letters
Volume
161
Issue
2
Publish Date
2006
Start Page
135
End Page
142
DOI
10.1016/j.toxlet.2005.08.011

Novel heparanase-inhibiting antibody reduces neointima formation

Basic fibroblast growth factor (bFGF), stored bound to heparan sulfate proteoglycans in the extracellular matrix (ECM) of the arterial media, may initiate smooth muscle cell (SMC) proliferation after coronary intervention, thus contributing to restenosis. bFGF mobilization from ECM stores after injury may be induced by platelet degranulation products such as heparanase. Therapies aimed at the inhibition of bFGF release and activation may assist in prevention of restenosis. To test this theory, we first examined the mobilization and activation of bFGF in the arterial media by platelet-derived heparanase. Heparanase, locally delivered to the rat carotid artery, was found to release bFGF and induce substantial SMC proliferation in the absence of actual vascular injury. An antibody that neutralizes heparanase was then developed and evaluated in a rat carotid balloon injury model. Local delivery of anti-heparanase IgG was found to inhibit bFGF release by approximately 60% (p < 0-001) at 4 d; this correlated with the significant reduction in neointima formation observed at 14 d (intimal area/medial area: control 1.3 ± 0.3, anti-heparanase 0.35 ± 0.12, p < 0.0001). Platelet-derived heparanase is therefore likely to be important in initiating events leading to restenosis via bFGF mobilization. Furthermore, heparanase neutralization may assist in the prevention of restenosis following vascular injury. © 2006 The Japanese Biochemical Society.

Authors
Myler, HA; Lipke, EA; Rice, EE; West, JL
MLA Citation
Myler, HA, Lipke, EA, Rice, EE, and West, JL. "Novel heparanase-inhibiting antibody reduces neointima formation." Journal of Biochemistry 139.3 (2006): 339-345.
PMID
16567398
Source
scival
Published In
The Journal of Biochemistry
Volume
139
Issue
3
Publish Date
2006
Start Page
339
End Page
345
DOI
10.1093/jb/mvj061

Nanoshells as contrast agents for scatter-based optical imaging

Optical properties of gold nanoshell-based contrast agents for optical coherence tomography (OCT) were determined using calculations based on concentric sphere Mie scattering theory. Nanoshells capable of optimal optical scattering in the near infrared (NIR) were subsequently fabricated. We show that scattering nanoshell possess higher backscattering efficiencies at longer wavelengths. Results show enhanced OCT signal intensities after addition of gold nanoshells to scattering tissue phantoms. In addition, in vivo mouse tumor model studies show clear evidence of enhancement of tumor scatter after nanoshell injection as compared to control (Phosphate Buffered Saline, PBS) injections, further demonstrating the potential of gold nanoshells as NIR contrast agents to improve scattering-based optical imaging technologies. In addition to the data shown in this preliminary paper, the talk will present more recent data using immunotargeted nanoshells for molecular contrast OCT. © 2006 IEEE.

Authors
Lee, M-H; Nammalvar, V; Gobin, A; Barton, J; West, J; Drezek, R
MLA Citation
Lee, M-H, Nammalvar, V, Gobin, A, Barton, J, West, J, and Drezek, R. "Nanoshells as contrast agents for scatter-based optical imaging." 2006 3rd IEEE International Symposium on Biomedical Imaging: From Nano to Macro - Proceedings 2006 (2006): 371-374.
Source
scival
Published In
2006 3rd IEEE International Symposium on Biomedical Imaging: From Nano to Macro - Proceedings
Volume
2006
Publish Date
2006
Start Page
371
End Page
374

Biomimetic microcontrolled materials for guiding cell migration

Authors
Hahn, M; West, JL
MLA Citation
Hahn, M, and West, JL. "Biomimetic microcontrolled materials for guiding cell migration." AIChE Annual Meeting, Conference Proceedings (2006).
Source
scival
Published In
AIChE Annual Meeting, Conference Proceedings
Publish Date
2006

Protease-activated quantum dot probes

We demonstrate a novel quantum dot based probe with inherent signal amplification upon interaction with a targeted proteolytic enzyme. This probe may be useful for imaging in cancer detection and diagnosis. In this system, quantum dots (QDs) are bound to gold nanoparticles (AuNPs) via a proteolytically-degradable peptide sequence to non-radiatively suppress luminescence. A 71% reduction in luminescence was achieved with conjugation of AuNPs to QDs. Peptide cleavage results in release of AuNPs and restores radiative QD photoluminescence. Initial studies observed a 52% rise in luminescence over 47 hours of exposure to 0.2 mg/mL collagenase. These probes can be customized for targeted degradation simply by changing the sequence of the peptide linker.

Authors
Chang, E; Sun, J; Miller, JS; Yu, WW; Calvin, VL; West, JL; Drezek, R
MLA Citation
Chang, E, Sun, J, Miller, JS, Yu, WW, Calvin, VL, West, JL, and Drezek, R. "Protease-activated quantum dot probes." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 6191 (2006).
Source
scival
Published In
Proceedings of SPIE
Volume
6191
Publish Date
2006
DOI
10.1117/12.660485

Nanoshell exogenous absorbers enable tissue welds

Authors
West, JL
MLA Citation
West, JL. "Nanoshell exogenous absorbers enable tissue welds." Advanced Materials and Processes 164.1 (2006): 79--.
Source
scival
Published In
Advanced Materials and Processes
Volume
164
Issue
1
Publish Date
2006
Start Page
79-

Immunonanoshells for selective photothermal therapy.

Authors
Lowery, AR; Gobin, AM; Day, ES; Shah, KY; Halas, NJ; West, JL
MLA Citation
Lowery, AR, Gobin, AM, Day, ES, Shah, KY, Halas, NJ, and West, JL. "Immunonanoshells for selective photothermal therapy." CLINICAL CANCER RESEARCH 11.24 (December 2005): 9097S-9097S. (Academic Article)
Source
manual
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
11
Issue
24
Publish Date
2005
Start Page
9097S
End Page
9097S

Nanoshells for combined cancer therapy and imaging in vivo.

Authors
Gobin, AM; Lee, MH; Drezek, RA; Halas, NJ; West, JL
MLA Citation
Gobin, AM, Lee, MH, Drezek, RA, Halas, NJ, and West, JL. "Nanoshells for combined cancer therapy and imaging in vivo." CLINICAL CANCER RESEARCH 11.24 (December 2005): 9095S-9095S. (Academic Article)
Source
manual
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
11
Issue
24
Publish Date
2005
Start Page
9095S
End Page
9095S

Diagnostic and Therapeutic Applications of Metal Nanoshells

Authors
Loo, C; Lin, A; Hirsch, L; Lee, MH; Barton, J; Halas, N; West, J; Drezek, R
MLA Citation
Loo, C, Lin, A, Hirsch, L, Lee, MH, Barton, J, Halas, N, West, J, and Drezek, R. "Diagnostic and Therapeutic Applications of Metal Nanoshells." (April 12, 2005): 327-342. (Chapter)
Source
scopus
Publish Date
2005
Start Page
327
End Page
342
DOI
10.1002/3527603476.ch12

Bio-nano interface: Examining the interactions between water-soluble fullerenes and biological membranes.

Authors
Sayes, CM; Ausman, KD; West, JL; Colvin, VL
MLA Citation
Sayes, CM, Ausman, KD, West, JL, and Colvin, VL. "Bio-nano interface: Examining the interactions between water-soluble fullerenes and biological membranes." ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 229 (March 2005): U911-U911. (Academic Article)
Source
manual
Published In
ACS National Meeting Book of Abstracts
Volume
229
Publish Date
2005
Start Page
U911
End Page
U911

Neutrophil integrin dependent activity

Authors
Gonzalez, AL; West, JL; McIntire, LV; Smith, CW
MLA Citation
Gonzalez, AL, West, JL, McIntire, LV, and Smith, CW. "Neutrophil integrin dependent activity." FASEB JOURNAL 19.4 (March 2005): A341-A341. (Academic Article)
Source
manual
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
19
Issue
4
Publish Date
2005
Start Page
A341
End Page
A341

Independent optical control of microfluidic valves formed from optomechanically responsive nanocomposite hydrogels

Independent optical control of two valves at a junction within a microfluidic device formed from a optomechanically responsive nanocomposite hydrogels was analyzed. Nanocomposite-hydrogel valves were formed by photopolymerizing the monomer mixture, with the inclusion of the appropriate nanoparticles, within a microfluidic device at a T-junction. It was shown that the lower critical solution temperature (LCST) of the temperature-responsive material could be tailored by altering the copolymer composition. By raising the LCST, one could also use absorbing materials with slightly overlapping absorption curves, since slight heating in non-targeted valve materials would not result in a phase change, allowing the valve to remain close.

Authors
Sershen, SR; Mensing, GA; Ng, M; Halas, NJ; Beebe, DJ; West, JL
MLA Citation
Sershen, SR, Mensing, GA, Ng, M, Halas, NJ, Beebe, DJ, and West, JL. "Independent optical control of microfluidic valves formed from optomechanically responsive nanocomposite hydrogels." Advanced Materials 17.11 (2005): 1366-1368.
Source
scival
Published In
Advanced Materials
Volume
17
Issue
11
Publish Date
2005
Start Page
1366
End Page
1368
DOI
10.1002/adma.200401239

Covalent immobilization of RGDS on hydrogel surfaces to direct cell alignment and migration

This study extends the capability for directing cell behavior using PEG-based hydrogels in tissue-engineering applications to include control over the spatial distribution of the adhesive peptide, RGDS. A continuous linear gradient was formed by simultaneously using a gradient maker to combine precursor solutions and using photopolymerization to lock the RGDS gradient in place. Hydrogels containing entrapped gradients of bovine serum albumin (BSA) were characterized using Coomassie brilliant blue stain, which indicated that BSA concentration increases along the hydrogel's length and that the steepness of the gradient's slope can be varied by changing the relative BSA concentrations in the precursor solutions. Human dermal fibroblasts responded to covalently immobilized RGDS gradients by changing their morphology to align in the direction of increasing RGDS concentration. After 24 h, ∼46% of fibroblasts were aligned with the RGDS-gradient axis. This proportion of cells further increased to ∼53% (p < 0.05) and ∼58% after 48 and 96 h, respectively. Also, fibroblasts migrated differentially depending on the concentration of RGDS. Fibroblasts migrated ∼48% further going up the concentration gradient (0 to 6 μmol/ml PEG-RGDS) than going down the concentration gradient. Migration up the concentration gradient was also ∼33% greater than migration on control surfaces with a constant concentration of RGDS (2 μmol/ml), while migration down the gradient was reduced ∼12% relative to the control surface. In addition, directed migration was further enhanced by increasing the RGDS gradient's slope. This hydrogel system is expected to be useful for directing cell migration to enhance the formation of engineered tissues. © 2005 Elsevier B.V. All rights reserved.

Authors
DeLong, SA; Gobin, AS; West, JL
MLA Citation
DeLong, SA, Gobin, AS, and West, JL. "Covalent immobilization of RGDS on hydrogel surfaces to direct cell alignment and migration." Journal of Controlled Release 109.1-3 (2005): 139-148.
PMID
16290119
Source
scival
Published In
Journal of Controlled Release
Volume
109
Issue
1-3
Publish Date
2005
Start Page
139
End Page
148
DOI
10.1016/j.jconrel.2005.09.020

Protease-activated quantum dot probes

We have developed a novel nanoparticulate luminescent probe with inherent signal amplification upon interaction with a targeted proteolytic enzyme. This construct may be useful for imaging in cancer detection and diagnosis. In this system, quantum dots (QDs) are bound to gold nanoparticles (AuNPs) via a proteolytically degradable peptide sequence to non-radiatively suppress luminescence. A 71% reduction in luminescence was achieved with conjugation of AuNPs to QDs. Release of AuNPs by peptide cleavage restores radiative QD photoluminescence. Initial studies observed a 52% rise in luminescence over 47 h of exposure to 0.2 mg/mL collagenase. These probes can be customized for targeted degradation simply by changing the sequence of the peptide linker. © 2005 Elsevier Inc. All rights reserved.

Authors
Chang, E; Miller, JS; Sun, J; Yu, WW; Colvin, VL; Drezek, R; West, JL
MLA Citation
Chang, E, Miller, JS, Sun, J, Yu, WW, Colvin, VL, Drezek, R, and West, JL. "Protease-activated quantum dot probes." Biochemical and Biophysical Research Communications 334.4 (2005): 1317-1321.
PMID
16039606
Source
scival
Published In
Biochemical and Biophysical Research Communications
Volume
334
Issue
4
Publish Date
2005
Start Page
1317
End Page
1321
DOI
10.1016/j.bbrc.2005.07.028

Nitric oxide-producing polyurethanes

Thrombus formation and eventual intimal hyperplasia are the leading causes of small-diameter synthetic vascular graft failure. To combat these issues, we have incorporated a diazeniumdiolate-modified nitric oxide (NO)-producing peptide into a polyurethane to improve the thromboresistance of this biocompatible polymer. NO production by polyurethane films occurred for approximately 2 months under physiological conditions, and mechanical properties of the material were suitable for vascular graft applications. Platelet adhesion to NO-releasing polyurethane was dramatically decreased compared to control polyurethane. Furthermore, endothelial cell growth was stimulated in the presence of the NO-releasing polyurethane, while smooth muscle cell growth was greatly inhibited. The ability of this bioactive material to inhibit platelet adhesion and smooth muscle cell proliferation while encouraging endothelialization suggests that this NO-generating polyurethane may be suitable as a candidate material for small-diameter vascular grafts. © 2005 American Chemical Society.

Authors
Jun, H-W; Taite, LJ; West, JL
MLA Citation
Jun, H-W, Taite, LJ, and West, JL. "Nitric oxide-producing polyurethanes." Biomacromolecules 6.2 (2005): 838-844.
PMID
15762649
Source
scival
Published In
Biomacromolecules
Volume
6
Issue
2
Publish Date
2005
Start Page
838
End Page
844
DOI
10.1021/bm049419y

Optically tunable nanoparticle contrast agents for early cancer detection: Model-based analysis of gold nanoshells

Many optical diagnostic approaches rely on changes in scattering and absorption properties to generate optical contrast between normal and diseased tissue. Recently, there has been increasing interest in using exogenous agents to enhance this intrinsic contrast with particular emphasis on the development for targeting specific molecular features of disease. Gold nanoshells are a class of core-shell nanoparticles with an extremely tunable peak optical resonance ranging from the near-UV to the mid-IR wavelengths. Using current chemistries, nanoshells of a wide variety of core and shell sizes can easily be fabricated to scatter and/or absorb light with optical cross sections often several times larger than the geometric cross section. Using gold nanoshells of different size and optical parameters, we employ Monte Carlo models to predict the effect of varying concentrations of nanoshells on tissue reflectance. The models demonstrate the importance of absorption from the nanoshells on remitted signals even when the optical extinction is dominated by scattering. Furthermore, because of the strong optical response of nanoshells, a considerable change in reflectance is observed with only a very small concentration of nanoshells. Characterizing the optical behavior of gold nanoshells in tissue will aid in developing nanoshells as contrast agents for optical diagnostics. © 2005 Society of Photo-Optical Instrumentation Engineers.

Authors
Lin, AWH; Lewinski, NA; West, JL; Halas, NJ; Drezek, RA
MLA Citation
Lin, AWH, Lewinski, NA, West, JL, Halas, NJ, and Drezek, RA. "Optically tunable nanoparticle contrast agents for early cancer detection: Model-based analysis of gold nanoshells." Journal of Biomedical Optics 10.6 (2005).
PMID
16409100
Source
scival
Published In
Journal of Biomedical Optics
Volume
10
Issue
6
Publish Date
2005
DOI
10.1117/1.2141825

Modification of polyurethaneurea with PEG and YIGSR peptide to enhance endothelialization without platelet adhesion

Improved endothelialization without platelet adhesion is essential to enhance the long-term patency of synthetic vascular grafts and other blood-contacting devices. We have developed a dually modified polyurethaneurea by incorporating endothelial cell adhesive YIGSR peptide sequences as chain extenders and nonthrombogenic PEG as a soft segment (PUUYIGSR-PEG) in the polymer backbone. PUUYIGSR-PEG was successfully synthesized and characterized by proton NMR, FTIR, GPC, DSC, ESCA, and contact angle measurement. Despite having similar molecular weight, the peptide/PEG-modified polyurethaneurea (PUUYIGSR-PEG) showed superior mechanical properties compared to the control PEG-modified polyurethaneurea (PUUPPD-PEG). Virtually no platelet adhesion was observed on PUUYIGSR-PEG, while endothelial cell adhesion, spreading, and migration were significantly greater on PUUYIGSR-PEG compared to PUUPPD-PEG. Thus, this bioactive polymer may be an appropriate biomaterial for small diameter vascular grafts. © 2004 Wiley Periodicals, Inc.

Authors
Jun, H-W; West, JL
MLA Citation
Jun, H-W, and West, JL. "Modification of polyurethaneurea with PEG and YIGSR peptide to enhance endothelialization without platelet adhesion." Journal of Biomedical Materials Research - Part B Applied Biomaterials 72.1 (2005): 131-139.
PMID
15389489
Source
scival
Published In
Journal of Biomedical Materials Research
Volume
72
Issue
1
Publish Date
2005
Start Page
131
End Page
139
DOI
10.1002/jbm.b.30135

Localized delivery of nitric oxide from hydrogels inhibits neointima formation in a rat carotid balloon injury model

Using novel nitric oxide (NO)-generating polymeric hydrogels that can be rapidly photopolymerized in situ, we can deliver NO locally at the site of vascular injury. Depending on material design, these poly(ethylene glycol) (PEG)-based hydrogels can generate NO for up to 50 d. This study demonstrates the ability of nitric oxide-generating hydrogels (PEG-Cys-NO) to influence key components of the restenosis cascade both in vitro and in vivo. PEG-Cys-NO hydrogels inhibited smooth muscle cell proliferation, increased endothelial cell proliferation, and inhibited platelet adhesion in vitro. Moreover, in vivo, PEG-Cys-NO hydrogels inhibited intimal thickening in a rat carotid balloon injury model. The perivascular application of NO-generating polymers post-injury reduced neointima formation at 14 d by approximately 80% compared to controls (intimal area/medial area (I/M): PEG-Cys-NO = 0.20 ± 0.17, control = 0.84 ± 0.19, p < 0.00002; intimal thickness: PEG-Cys-NO = 12 ±10 μm, control = 60 ± 18 μm, p < 0.00002). Treatment with the PEG-Cys-NO hydrogels caused a significant decrease in the per cent of proliferating cell nuclear antigen positive medial cells (29 ± 5%) at 4 d as compared to treatment with the control hydrogels (51 ± 1%, p < 0.02). Additionally, vessel re-endothelialization at 14 d was slightly enhanced in the presence of the NO-generating hydrogels. These data indicate that localized delivery of NO from these hydrogels can significantly inhibit neointima formation in a rat carotid balloon injury model and suggest that these materials may be useful in preventing restenosis. © 2005 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Authors
Lipke, EA; West, JL
MLA Citation
Lipke, EA, and West, JL. "Localized delivery of nitric oxide from hydrogels inhibits neointima formation in a rat carotid balloon injury model." Acta Biomaterialia 1.6 (2005): 597-606.
PMID
16701840
Source
scival
Published In
Acta Biomaterialia
Volume
1
Issue
6
Publish Date
2005
Start Page
597
End Page
606
DOI
10.1016/j.actbio.2005.07.010

Nitric oxide-generating hydrogels inhibit neointima formation

This study evaluated the effects of localized delivery of nitric oxide (NO) from hydrogels covalently modified with S-nitrosocysteine (Cys-NO) on neoinitma formation, a key component of restenosis, in a rat balloon-injury model. Soluble Cys-NO was used in preliminary studies to identify dosage ranges that were able to simultaneously inhibit smooth muscle cell proliferation, enhance endothelial cell proliferation, and reduce platelet adhesion. Photo-cross-linked PEG-based hydrogels were formed with covalently immobilized Cys-NO. These materials release NO for approximately 24 h and can be applied to tissues and photo-cross-linked in situ to form local drug-delivery systems. Localized delivery of NO from hydrogels containing Cys-NO inhibited neointima formation in a rat balloon-injury model by approximately 75% at 14 days. © VSP 2005.

Authors
Masters, KSB; Lipke, EA; Rice, EE; Liel, MS; Myler, HA; Zygourakis, C; Tulis, DA; West, JL
MLA Citation
Masters, KSB, Lipke, EA, Rice, EE, Liel, MS, Myler, HA, Zygourakis, C, Tulis, DA, and West, JL. "Nitric oxide-generating hydrogels inhibit neointima formation." Journal of Biomaterials Science, Polymer Edition 16.5 (2005): 659-672.
PMID
16001723
Source
scival
Published In
Journal of Biomaterials Science, Polymer Edition
Volume
16
Issue
5
Publish Date
2005
Start Page
659
End Page
672
DOI
10.1163/1568562053783722

Poly(ethylene glycol) hydrogel system supports preadipocyte viability, adhesion, and proliferation

The ultimate goal of this research is to develop an injectable cell-scaffold system capable of permitting adipogenesis to abrogate soft tissue deficiencies resulting from trauma, tumor resection, and congenital abnormalities. The present work compares the efficacy of photopolymerizable poly(ethylene glycol) and specific derivatives as a scaffold for preadipocyte (adipocyte precursor cell) viability, adhesion, and proliferation. Four variations of a poly(ethylene glycol) scaffold are prepared and examined. The first scaffold consists of poly(ethylene glycol) diacrylate, which is not susceptible to hydrolysis or enzymatic degradation. Preadipocyte death is observed over 1 week in this hydrogel configuration. Adhesion sites, specifically the laminin-binding peptide sequence YIGSR, were incorporated into the second scaffold to promote cellular adhesion as a prerequisite for preadipocyte proliferation. Preadipocytes remain viable in this scaffold system, but do not proliferate in this nondegradable hydrogel. The third scaffold system studied consists of poly(ethylene glycol) modified with the peptide sequence LGPA to permit polymer degradation by cell-secreted collagenase. No adhesion peptide is incorporated into this scaffold system. Cellular proliferation is initially observed, followed by cell death. The previous three scaffold configurations do not permit preadipocyte adhesion and proliferation. In contrast, the fourth system studied, poly(ethylene glycol) modified to incorporate both LGPA and YIGSR, permits preadipocyte adherence and proliferation subsequent to polymer degradation. Our results indicate that a scaffold system containing specific degradation sites and cell adhesion ligands permits cells to adhere and proliferate, thus providing a potential cell-scaffold system for adipogenesis. © Mary Ann Liebert, Inc.

Authors
Patel, PN; Gobin, AS; West, JL; Jr, CWP
MLA Citation
Patel, PN, Gobin, AS, West, JL, and Jr, CWP. "Poly(ethylene glycol) hydrogel system supports preadipocyte viability, adhesion, and proliferation." Tissue Engineering 11.9-10 (2005): 1498-1505.
PMID
16259604
Source
scival
Published In
Tissue Engineering
Volume
11
Issue
9-10
Publish Date
2005
Start Page
1498
End Page
1505
DOI
10.1089/ten.2005.11.1498

Laser scanning lithography for surface micropatterning on hydrogels

A versatile confocal-based laser scanning lithographic method for controlled, high-fidelity two-dimensional (2D) and three-dimensional (3D) surface patterning of poly(ethylene glycol)-diacrylate (PEGDA) hydrogels was presented. The surface properties of deformable PEGDA hydrogels were modified using laser scanning lithography (LSL), with pattern feature sizes down to at least 5 μm. Complex 2D concentration gradients of patterned peptides were generated through user alteration of irradiation exposure levels across regions of interest (ROI). 3D surface structures with heights under ∼5 were also created with high fidelity by incorporating PEGDA macromers into the precursor solution.

Authors
Hahn, MS; Miller, JS; West, JL
MLA Citation
Hahn, MS, Miller, JS, and West, JL. "Laser scanning lithography for surface micropatterning on hydrogels." Advanced Materials 17.24 (2005): 2939-2942.
Source
scival
Published In
Advanced Materials
Volume
17
Issue
24
Publish Date
2005
Start Page
2939
End Page
2942
DOI
10.1002/adma.200500184

Covalently immobilized gradients of bFGF on hydrogel scaffolds for directed cell migration

Basic fibroblast growth factor (bFGF) was immobilized to hydrogel scaffolds with retention of mitogenic and chemotactic activity. The bFGF was functionalized in order to incorporate it covalently within polyethylene glycol (PEG) hydrogel scaffolds by reaction with acryloyl-PEG-NHS. Hydrogels were formed by exposing aqueous solutions of PEG diacrylate, acryloyl-PEG-RGDS, and acryloyl-PEG-bFGF to long-wavelength ultraviolet light in the presence of a photoinitiator. These bFGF-modified hydrogels with RGD adhesion sites were evaluated for their effect on vascular smooth muscle cell (SMC) behavior, increasing SMC proliferation by ∼41% and migration by ∼15%. A covalently immobilized bFGF gradient was formed using a gradient maker to pour the hydrogel precursor solutions and then photopolymerizing to lock in the concentration gradient. Silver staining was used to detect the bFGF gradient, which increased linearly along the hydrogel's length. Cells were observed to align on hydrogels modified with a bFGF gradient in the direction of increasing tethered bFGF concentration as early as 24 h after seeding. SMCs also migrated differentially, up the concentration gradient, on bFGF-gradient hydrogels compared to control hydrogels with and without a constant bFGF concentration. These hydrogel scaffolds may be useful for studying protein gradient effects on cell behavior and for directing cell migration in tissue-engineering applications. © 2004 Elsevier Ltd. All rights reserved.

Authors
DeLong, SA; Moon, JJ; West, JL
MLA Citation
DeLong, SA, Moon, JJ, and West, JL. "Covalently immobilized gradients of bFGF on hydrogel scaffolds for directed cell migration." Biomaterials 26.16 (2005): 3227-3234.
PMID
15603817
Source
scival
Published In
Biomaterials
Volume
26
Issue
16
Publish Date
2005
Start Page
3227
End Page
3234
DOI
10.1016/j.biomaterials.2004.09.021

Proteolytically degradable hydrogels with a fluorogenic substrate for studies of cellular proteolytic activity and migration

We have developed proteolytically degradable hydrogels with covalently immobilized fluorogenic protease substrates to visualize extracellular proteolytic activity and cell migration in three dimensions. Dye quenched-bovine serum albumin (DQ-BSA), a quenched, proteolytically activated fluorogenic substrate, was conjugated to poly-(ethylene glycol) (PEG)-monoacrylate, and the product (DQ-BSA-PEG) was then covalently incorporated into proteolytically degradable and cell adhesive PEG hydrogels via photopolymerization. The DQ-BSA-PEG substrate in solution and incorporated into hydrogels exhibited significantly enhanced fluorescence after exposure to enzymes. Fibroblasts seeded within this hydrogel spread in three dimensions and extended lamellipodia. Cell migration and proteolytic activity were visualized using confocal microscopy. Proteolytic activity was concentrated near cell surfaces and remained present in the tracks where cell migration had occurred. © 2005 American Chemical Society and American Institute of Chemical Engineers.

Authors
Lee, S-H; Miller, JS; Moon, JJ; West, JL
MLA Citation
Lee, S-H, Miller, JS, Moon, JJ, and West, JL. "Proteolytically degradable hydrogels with a fluorogenic substrate for studies of cellular proteolytic activity and migration." Biotechnology Progress 21.6 (2005): 1736-1741.
PMID
16321059
Source
scival
Published In
Biotechnology Progress
Volume
21
Issue
6
Publish Date
2005
Start Page
1736
End Page
1741
DOI
10.1021/bp0502429

Near infrared laser-tissue welding using nanoshells as an exogenous absorber

Background and Objective: Gold nanoshells are a new class of nanoparticles that can be designed to strongly absorb light in the near infrared (NIR). These particles provide much larger absorption cross-sections and efficiency than can be achieved with currently used chemical chromophores without photobleaching. In these studies, we have investigated the use of gold nanoshells as exogenous NIR absorbers to facilitate NIR laser-tissue welding. Study Design/Materials and Methods: Gold nanoshells with peak extinction matching the NIR wavelength of the laser being used were manufactured and suspended in an albumin solder. Optimization work was performed on ex vivo muscle samples and then translated into testing in an in vivo rat skin wound-healing model. Mechanical testing of the muscle samples was immediately performed and compared to intact tissue mechanical properties. In the in vivo study, full thickness incisions in the dorsal skin of rats were welded, and samples of skin were excised at 0, 5, 10, 21, and 32 days for analysis of strength and wound healing response. Results: Mechanical testing of nanoshell-solder welds in muscle revealed successful fusion of tissues with tensile strengths of the weld site equal to the uncut tissue. No welding was accomplished with this light source when using solder formulations without nanoshells. Mechanical testing of the skin wounds showed sufficient strength for closure and strength increased over time. Histological examination showed good wound-healing response in the soldered skin. Conclusions: The use of nanoshells as an exogenous absorber allows the usage of light sources that are minimally absorbed by tissue components, thereby, minimizing damage to surrounding tissue and allowing welding of thicker tissues. © 2005 Wiley-Liss, Inc.

Authors
Gobin, AM; O'Neal, DP; Watkins, DM; Halas, NJ; Drezek, RA; West, JL
MLA Citation
Gobin, AM, O'Neal, DP, Watkins, DM, Halas, NJ, Drezek, RA, and West, JL. "Near infrared laser-tissue welding using nanoshells as an exogenous absorber." Lasers in Surgery and Medicine 37.2 (2005): 123-129.
PMID
16047329
Source
scival
Published In
Lasers in Surgery and Medicine
Volume
37
Issue
2
Publish Date
2005
Start Page
123
End Page
129
DOI
10.1002/lsm.20206

Endothelialization of microporous YIGSR/PEG-modified polyurethaneurea

Bioactive polyurethaneurea modified with polyethylene glycol (PEG) and the endothelial cell-adhesive peptide YIGSR was synthesized and fabricated into microporous scaffolds. This material has shown appropriate mechanical properties for vascular graft applications, resists platelet adhesion, and promotes endothelialization. In the current study, microporous scaffolds were formed by a gas-foaming and salt-leaching method. The scaffolds showed highly interconnected open pores throughout the matrices, with porosity of approximately 78% and pore sizes of 20-200 μm. The peptide modified scaffolds showed superior mechanical properties over peptide-free scaffolds (tensile strength, 1.4 ± 0.03 versus 0.19 ± 0.01 MPa; p < 0.01). Bovine aortic endothelial cells were seeded on the scaffolds, and cell attachment, proliferation, extracellular matrix production, and migration were investigated. Histological and scanning electron microscopy analysis showed that few cells adhered on peptide-free scaffolds, whereas confluent endothelial cell monolayers formed along the pores in peptide-modified scaffolds. DNA content, hydroxyproline production, and cell migration were also significantly greater in peptide-modified scaffolds. © Mary Ann Liebert, Inc.

Authors
Jun, H-W; West, JL
MLA Citation
Jun, H-W, and West, JL. "Endothelialization of microporous YIGSR/PEG-modified polyurethaneurea." Tissue Engineering 11.7-8 (2005): 1133-1140.
PMID
16144449
Source
scival
Published In
Tissue Engineering
Volume
11
Issue
7-8
Publish Date
2005
Start Page
1133
End Page
1140
DOI
10.1089/ten.2005.11.1133

Nano-C60 cytotoxicity is due to lipid peroxidation

This study examines the biological effects of water-soluble fullerene aggregates in an effort to evaluate the fundamental mechanisms that contribute to the cytotoxicity of a classic engineered nanomaterial. For this work we used a water-soluble fullerene species, nano-C60, a fullerene aggregate that readily forms when pristine C60 is added to water. Nano-C 60 was cytotoxic to human dermal fibroblasts, human liver carcinoma cells (HepG2), and neuronal human astrocytes at doses ≥50 ppb (LC 50=2-50 ppb, depending on cell type) after 48 h exposure. This water-soluble nano-C60 colloidal suspension disrupts normal cellular function through lipid peroxidation; reactive oxygen species are responsible for the membrane damage. Cellular viability was determined through live/dead staining and LDH release. DNA concentration and mitochondrial activity were not affected by the nano-C60 inoculations to cells in culture. The integrity of cellular membrane was examined by monitoring the peroxy-radicals on the lipid bilayer. Subsequently, glutathione production was measured to assess the cell's reaction to membrane oxidation. The damage to cell membranes was observed both with chemical assays, and confirmed physically by visualizing membrane permeability with high molecular weight dyes. With the addition of an antioxidant, l-ascorbic acid, the oxidative damage and resultant toxicity of nano-C60 was completely prevented. © 2005 Elsevier Ltd. All rights reserved.

Authors
Sayes, CM; Gobin, AM; Ausman, KD; Mendez, J; West, JL; Colvin, VL
MLA Citation
Sayes, CM, Gobin, AM, Ausman, KD, Mendez, J, West, JL, and Colvin, VL. "Nano-C60 cytotoxicity is due to lipid peroxidation." Biomaterials 26.36 (2005): 7587-7595.
PMID
16005959
Source
scival
Published In
Biomaterials
Volume
26
Issue
36
Publish Date
2005
Start Page
7587
End Page
7595
DOI
10.1016/j.biomaterials.2005.05.027

Gold nanoshell bioconjugates for molecular imaging in living cells

Advances in scattering-based optical imaging technologies offer a new approach to noninvasive point-of-care detection, diagnosis, and monitoring of cancer. Emerging photonics technologies provide a cost-effective means to image tissue in vivo with high resolution in real time. Advancing the clinical potential of these imaging strategies requires the development of optical contrast agents targeted to specific molecular signatures of disease. We describe the use of a novel class of contrast agents based on nanoshell bioconjugates for molecular imaging in living cells. Nanoshells offer significant advantages over conventional imaging probes including continuous and broad wavelength tunability, far greater scattering and absorption coefficients, increased chemical stability, and improved biocompatibility. We show that nanoshell bioconjugates can be used to effectively target and image human epidermal growth factor receptor 2 (HER2), a clinically relevant biomarker, in live human breast carcinoma cells. © 2005 Optical Society of America.

Authors
Loo, C; Hirsch, L; Lee, M-H; Chang, E; West, J; Halas, N; Drezek, R
MLA Citation
Loo, C, Hirsch, L, Lee, M-H, Chang, E, West, J, Halas, N, and Drezek, R. "Gold nanoshell bioconjugates for molecular imaging in living cells." Optics Letters 30.9 (2005): 1012-1014.
PMID
15906987
Source
scival
Published In
Optics Letters
Volume
30
Issue
9
Publish Date
2005
Start Page
1012
End Page
1014
DOI
10.1364/OL.30.001012

Immunotargeted nanoshells for integrated cancer imaging and therapy

Nanoshells are a novel class of optically tunable nanoparticles that consist of a dielectric core surrounded by a thin gold shell. Based on the relative dimensions of the shell thickness and core radius, nanoshells may be designed to scatter and/or absorb light over a broad spectral range including the near-infrared (NIR), a wavelength region that provides maximal penetration of light through tissue. The ability to control both wavelength-dependent scattering and absorption of nanoshells offers the opportunity to design nanoshells which provide, in a single nanoparticle, both diagnostic and therapeutic capabilities. Here, we demonstrate a novel nanoshell-based all-optical platform technology for integrating cancer imaging and therapy applications. Immunotargeted nanoshells are engineered to both scatter light in the NIR enabling optical molecular cancer imaging and to absorb light, allowing selective destruction of targeted carcinoma cells through photothermal therapy. In a proof of principle experiment, dual imaging/therapy immunotargeted nanoshells are used to detect and destroy breast carcinoma cells that overexpress HER2, a clinically relevant cancer biomarker. © 2005 American Chemical Society.

Authors
Loo, C; Lowery, A; Halas, N; West, J; Drezek, R
MLA Citation
Loo, C, Lowery, A, Halas, N, West, J, and Drezek, R. "Immunotargeted nanoshells for integrated cancer imaging and therapy." Nano Letters 5.4 (2005): 709-711.
PMID
15826113
Source
scival
Published In
Nano Letters
Volume
5
Issue
4
Publish Date
2005
Start Page
709
End Page
711
DOI
10.1021/nl050127s

Laser scanning lithography for surface micropatterning on hydrogels

Authors
Hahn, MS; Miller, JS; West, JL
MLA Citation
Hahn, MS, Miller, JS, and West, JL. "Laser scanning lithography for surface micropatterning on hydrogels." AIChE Annual Meeting, Conference Proceedings (2005): 14117-14121.
Source
scival
Published In
AIChE Annual Meeting, Conference Proceedings
Publish Date
2005
Start Page
14117
End Page
14121

Laser tissue soldering with near-infrared absorbing nanoparticles

Gold nanoshells are a new class of nanoparticles with tunable optical absorption that can be placed in the near infrared. Gold nanoshells consist of a spherical silica core surrounded by a thin gold shell. The ratio of the sizes of the core diameter to the shell thickness as well as the total size of the nanoshell determines the optical absorption properties. Previous experiments have shown that these nanoparticles are stable at >325°C for durations typical of laser tissue welding. We have investigated the use of gold nanoshells as exogenous NIR absorbers to facilitate ex vivo laser tissue soldering. For ex vivo testing, gold nanoshells with peak absorption at approximately 820 nm were suspended in an albumin solder formulation and applied to muscle strips, followed by irradiation of the tissue at 821 nm. Mechanical testing of nanoshellsolder welds in muscle revealed successful fusion of tissues with tensile strengths of the weld site equal to the native tissue. The use of thermally stable nanoshells as an exogenous absorber allows the usage of light sources that are minimally absorbed by tissue components, thereby minimizing damage to surrounding tissue and producing welds sufficient for wound closure.

Authors
Gobin, AM; O'Neal, DP; Halas, NJ; Drezek, RA; West, JL
MLA Citation
Gobin, AM, O'Neal, DP, Halas, NJ, Drezek, RA, and West, JL. "Laser tissue soldering with near-infrared absorbing nanoparticles." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 5686 (2005): 261-266.
Source
scival
Published In
Proceedings of SPIE
Volume
5686
Publish Date
2005
Start Page
261
End Page
266
DOI
10.1117/12.590614

Whole-blood immunoassay facilitated by gold nanoshell-conjugate antibodies.

In this chapter, we outline a simple procedure using gold nanoshells as a substrate for an immunoassay that is capable of detecting subnanogram levels of analyte within whole blood on the order of minutes. Unique to metallic nanoshells is their optical tunability over a large range of wavelengths. We describe the design of nanoshells that attenuate light strongly in a region of light where blood does not (i.e., the near infrared [IR]), permitting optical detection of nanoshells in whole blood. We also describe a procedure to monitor the analyte-induced aggregation of antibody-conjugated nanoshells in whole blood using near-IR light. The immunoassay is fast and specific, requires no separation/purification steps, is simple to perform (mix and sit), and uses common laboratory equipment for detection (spectrophotometer). Preparation of the antibody-nanoshell conjugates is described, along with the design and optimization of the whole-blood nanoshell-based immunoassay system.

Authors
Hirsch, LR; Halas, NJ; West, JL
MLA Citation
Hirsch, LR, Halas, NJ, and West, JL. "Whole-blood immunoassay facilitated by gold nanoshell-conjugate antibodies." Methods in molecular biology (Clifton, N.J.) 303 (2005): 101-111.
PMID
15923678
Source
scival
Published In
Methods in molecular biology (Clifton, N.J.)
Volume
303
Publish Date
2005
Start Page
101
End Page
111

Photo-thermal cancer therapy using intravenously injected near infrared-absorbing nanoparticles

This report focuses on the treatment parameters leading to successful nanoshell-assisted photo-thermal therapy (NAPT). NAPT takes advantage of the strong near infrared (NIR) absorption of gold-silica nanoshells, a new class of nanoparticles with tunable optical absorptivities that are capable of passive extravasation from the abnormal tumor vasculature due to their nanoscale size. Under controlled conditions nanoshells accumulate in tumors with superior efficiency compared to surrounding tissues. For this treatment: (1) tumors were inoculated in immune-competent mice by subcutaneous injection, (2) polyethylene glycol coated nanoshells (≈150 nm diameter) with peak optical absorption in the NIR were intravenously injected and allowed to circulate for 6-48 hours, and (3) tumors were then extracorporeally illuminated with a collimated diode laser (808 nm, 2-6 W/cm2, 2-4 min). Nanoshell accumulations were quantitatively assessed in tumors and surrounding tissues using neutron activation analysis for gold. In order to assess temperature elevation, laser therapies were monitored in real-time using a mid-infrared thermal sensor. NAPT resulted in complete tumor regression in >90% of the subjects. This simple, noninvasive procedure shows great promise as a technique for selective photo-thermal tumor treatment.

Authors
O'Neal, DP; Hirsch, LR; Halas, NJ; Payne, JD; West, JL
MLA Citation
O'Neal, DP, Hirsch, LR, Halas, NJ, Payne, JD, and West, JL. "Photo-thermal cancer therapy using intravenously injected near infrared-absorbing nanoparticles." Progress in Biomedical Optics and Imaging - Proceedings of SPIE 5689 (2005): 149-157.
Source
scival
Published In
Proceedings of SPIE
Volume
5689
Publish Date
2005
Start Page
149
End Page
157
DOI
10.1117/12.590819

Distinct integrin mediated cell activity

Authors
Gonzalez, AL; Gobin, A; West, JL; McIntire, LV; Smith, CW
MLA Citation
Gonzalez, AL, Gobin, A, West, JL, McIntire, LV, and Smith, CW. "Distinct integrin mediated cell activity." FASEB JOURNAL 18.4 (March 2004): A69-A69. (Academic Article)
Source
manual
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
18
Issue
4
Publish Date
2004
Start Page
A69
End Page
A69

Integrin interactions with immobilized peptides in polyethylene glycol diacrylate hydrogels

This study employs tissue-engineering technologies to evaluate neutrophil interactions with extracellular matrix (ECM)-mimetic peptides. We have used a polyethylene glycol (PEG) diacrylate derivative to form a hydrogel as a biologically inert surface. Covalent attachment of bioactive moieties to the hydrogel makes it bioactive. The goal is to define the mechanisms by which these moieties influence the interactions of neutrophils with this bioactive hydrogel, and thus understand the likely effects of similar ligands in the ECM. The current experiments analyze the interactions of isolated human neutrophils with PEG hydrogels modified with Arg-Gly-Asp-Ser (RGDS), a known ligand for some β1 and β3 integrins, and Thr-Met-Lys-Ile-Ile- Pro-Phe-Asn-Arg-Leu-Thr-Ile-Gly-Gly (TMKIIPFNRLTIGG), a ligand for Mac-1, a β2 integrin. Our results demonstrate that neutrophils, independent of chemotactic stimulation, show little ability to adhere to unmodified PEG hydrogels. However, cell adhesion and spreading are robust on peptide-modified hydrogels. Incorporating distinct bioactive peptides, either alone or in combination, has enabled recognition of differential functions of αvβ3, and β2 integrins on neutrophil adhesion and spreading. Combined interactions result in activity that differs markedly from that seen with either integrin independently engaged. This model allows investigation of specific ligand-induced leukocyte functions and the development of engineered matrices with defined bioactive properties.

Authors
Gonzalez, AL; Gobin, AS; West, JL; McIntire, LV; Smith, CW
MLA Citation
Gonzalez, AL, Gobin, AS, West, JL, McIntire, LV, and Smith, CW. "Integrin interactions with immobilized peptides in polyethylene glycol diacrylate hydrogels." Tissue Engineering 10.11-12 (2004): 1775-1786.
PMID
15684686
Source
scival
Published In
Tissue Engineering
Volume
10
Issue
11-12
Publish Date
2004
Start Page
1775
End Page
1786

The differential cytotoxicity of water-soluble fullerenes

We show that the cytotoxicity of water-soluble fullerene species is a sensitive function of surface derivatization; in two different human cell lines, the lethal dose of fullerene changed over 7 orders of magnitude with relatively minor alterations in fullerene structure. In particular, an aggregated form of C60, the least derivatized of the four materials, was substantially more toxic than highly soluble derivatives such as C3, Na⊥ 2-3[C60O79(OH)12-15] (2-3)-, and C60(OH)24. Oxidative damage to the cell membranes was observed in all cases where fullerene exposure led to cell death. We show that under ambient conditions in water fullerenes can generate superoxide anions and postulate that these oxygen radicals are responsible for membrane damage and subsequent cell death. This work demonstrates both a strategy for enhancing the toxicity of fullerenes for certain applications such as cancer therapeutics or bactericides, as well as a remediation for the possible unwarranted biological effects of pristine fullerenes.

Authors
Sayes, CM; Fortner, JD; Guo, W; Lyon, D; Boyd, AM; Ausman, KD; Tao, YJ; Sitharaman, B; Wilson, LJ; Hughes, JB; West, JL; Colvin, VL
MLA Citation
Sayes, CM, Fortner, JD, Guo, W, Lyon, D, Boyd, AM, Ausman, KD, Tao, YJ, Sitharaman, B, Wilson, LJ, Hughes, JB, West, JL, and Colvin, VL. "The differential cytotoxicity of water-soluble fullerenes." Nano Letters 4.10 (2004): 1881-1887.
Source
scival
Published In
Nano Letters
Volume
4
Issue
10
Publish Date
2004
Start Page
1881
End Page
1887
DOI
10.1021/nl0489586

Nanoshell-Enabled Photonics-Based Imaging and Therapy of Cancer

Metal nanoshells are a novel type of composite spherical nanoparticle consisting of a dielectric core covered by a thin metallic shell which is typically gold. Nanoshells possess highly favorable optical and chemical properties for biomedical imaging and therapeutic applications. By varying the relative the dimensions of the core and the shell, the optical resonance of these nanoparticles can be precisely and systematically varied over a broad region ranging from the near-UV to the mid-infrared. This range includes the near-infrared (NIR) wavelength region where tissue transmissivity peaks. In addition to spectral tunability, nanoshells offer other advantages over conventional organic dyes including improved optical properties and reduced susceptibility to chemical/thermal denaturation. Furthermore, the same conjugation protocols used to bind biomolecules to gold colloid are easily modified for nanoshells. In this article, we first review the synthesis of gold nanoshells and illustrate how the core/shell ratio and overall size of a nanoshell influences its scattering and absorption properties. We then describe several examples of nanoshell-based diagnostic and therapeutic approaches including the development of nanoshell bioconjugates for molecular imaging, the use of scattering nanoshells as contrast agents for optical coherence tomography (OCT), and the use of absorbing nanoshells in NIR thermal therapy of tumors.

Authors
Loo, C; Lin, A; Hirsch, L; Lee, M-H; Barton, J; Halas, N; West, J; Drezek, R
MLA Citation
Loo, C, Lin, A, Hirsch, L, Lee, M-H, Barton, J, Halas, N, West, J, and Drezek, R. "Nanoshell-Enabled Photonics-Based Imaging and Therapy of Cancer." Technology in Cancer Research and Treatment 3.1 (2004): 33-40.
PMID
14750891
Source
scival
Published In
Technology in Cancer Research and Treatment
Volume
3
Issue
1
Publish Date
2004
Start Page
33
End Page
40

Nitric oxide-generating poly(ethylene glycol) copolymers for prevention of restenosis

Nitric oxide (NO)-generating poly(ethylene glycol) copolymers were synthesized and characterized for prevention of restenosis. Vessel re-endothelialization found to be slightly enhanced in the presence of the NO-generating hydrogels. The results indicate that localized delivery of NO from these hydrogels can significantly inhibit neointimal formation in a rat carotid balloon injury model. It was found that the combined effects of these hydrogels make them well suited for use as a stent coating or in endoluminal paving to prevent restenosis.

Authors
Lipke, EA; Masters, KS; West, JL
MLA Citation
Lipke, EA, Masters, KS, and West, JL. "Nitric oxide-generating poly(ethylene glycol) copolymers for prevention of restenosis." AIChE Annual Meeting, Conference Proceedings (2004): 6343-6344.
Source
scival
Published In
AIChE Annual Meeting, Conference Proceedings
Publish Date
2004
Start Page
6343
End Page
6344

Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles

The following study examines the feasibility of nanoshell-assisted photo-thermal therapy (NAPT). This technique takes advantage of the strong near infrared (NIR) absorption of nanoshells, a new class of gold nanoparticles with tunable optical absorptivities that can undergo passive extravasation from the abnormal tumor vasculature due to their nanoscale size. Tumors were grown in immune-competent mice by subcutaneous injection of murine colon carcinoma cells (CT26.WT). Polyethylene glycol (PEG) coated nanoshells (≈130 nm diameter) with peak optical absorption in the NIR were intravenously injected and allowed to circulate for 6 h. Tumors were then illuminated with a diode laser (808 nm, 4W/cm2, 3 min). All such treated tumors abated and treated mice appeared healthy and tumor free >90 days later. Control animals and additional sham-treatment animals (laser treatment without nanoshell injection) were euthanized when tumors grew to a predetermined size, which occurred 6-19 days post-treatment. This simple, non-invasive procedure shows great promise as a technique for selective photo-thermal tumor ablation. © 2004 Elsevier Ltd. All rights reserved.

Authors
O'Neal, DP; Hirsch, LR; Halas, NJ; Payne, JD; West, JL
MLA Citation
O'Neal, DP, Hirsch, LR, Halas, NJ, Payne, JD, and West, JL. "Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles." Cancer Letters 209.2 (2004): 171-176.
PMID
15159019
Source
scival
Published In
Cancer Letters
Volume
209
Issue
2
Publish Date
2004
Start Page
171
End Page
176
DOI
10.1016/j.canlet.2004.02.004

Nitric oxide-generating poly(ethylene glycol) copolymers for prevention of restenosis

The ability of nitric oxide (NO)-generating hydrogels to inhibit intimal thickening, a major component of restenosis, in a rat carotid injury model, was analyzed. NO-releasing materials were incubated at 37°C in HEPES buffer and assayed for NO release using the Griess assay. To examine cell proliferation, histological sections were immunostained for proliferating cell nuclear antigen (PCNA). Vessel re-endothelialization appeared to be slightly enhanced in the presence of the NO-generating hydrodgels. The results show that the combined effects of NO-generating hydrogels make them well suited for use as a stent coating or in endoluminal paving to prevent restenosis.

Authors
Lipke, EA; Masters, KS; West, JL
MLA Citation
Lipke, EA, Masters, KS, and West, JL. "Nitric oxide-generating poly(ethylene glycol) copolymers for prevention of restenosis." AIChE Annual Meeting, Conference Proceedings (2004): 8381-8382.
Source
scival
Published In
AIChE Annual Meeting, Conference Proceedings
Publish Date
2004
Start Page
8381
End Page
8382

Nitric oxide-generating poly(ethylene glycol) copolymers for prevention of restenosis

The use of nitric oxide-generating poly(ethylene glycol) (PEG) copolymers for prevention of restenosis was analyzed. PEG-NO-nucleophile was formed by reacting PEG N-hydroxysuccinimide monoacrylate (ACRL-PEG-NHS; MW 3.4 kDa) with cysteine (Cys). The resultant copolymer was dissolved in water and reacted with an equimolar amount of sodium nitrate at pH 2 to form the hydrogel precursor, PEG-Cys-NO. The results show that the PEG-Cys-NO hydrogels produced nitric oxide over a period of approximately 2 hr at pH 7.4, with most of the release occurring within the first 30 min.

Authors
Lipke, EA; Masters, KS; West, JL
MLA Citation
Lipke, EA, Masters, KS, and West, JL. "Nitric oxide-generating poly(ethylene glycol) copolymers for prevention of restenosis." AIChE Annual Meeting, Conference Proceedings (2004): 1261-1262.
Source
scival
Published In
AIChE Annual Meeting, Conference Proceedings
Publish Date
2004
Start Page
1261
End Page
1262

Inhibition of intimal thickening in a rat model of balloon angioplasty using NO-generating hydrogels

The ability of nitrogen oxide (NO)-generating hydrogels to inhibit thickening in a rat carotid injury model was discussed. It was observed that the perivascular application of NO-generating hydrogels reduced neointima formation in the balloon injury model as compared to control hydrogels. polyethylene glycol (PEG)-NO-nucleophile was formed by reacting polyethylene glycol N-hydroxysuccinimide monoacrylate with cysteine (Cys). It was found that the combined effects of NO-generating hydrogels made them suitable for use as a stent coating or in endoluminal paving to prevent restenosis.

Authors
Lipke, EA; West, JL
MLA Citation
Lipke, EA, and West, JL. "Inhibition of intimal thickening in a rat model of balloon angioplasty using NO-generating hydrogels." Transactions - 7th World Biomaterials Congress (2004): 397--.
Source
scival
Published In
Transactions - 7th World Biomaterials Congress
Publish Date
2004
Start Page
397-

Nanoshells for integrated diagnosis and therapy of cancer

Metal nanoshells are a novel type of composite nanoparticle consisting of a dielectric core covered by a thin metallic shell which is typically gold. Nanoshells possess highly favorable optical and chemical properties for biomedical imaging and therapeutic applications. By varying the relative the dimensions of the core and the shell, the optical resonance of these nanoparticles can be precisely and systematically varied over a broad wavelength region ranging from the near-UV to the mid-infrared. This range includes the near-infrared (NIR) region where tissue transmissivity peaks. In addition, nanoshells offer other advantages over conventional organic dye imaging agents, including improved optical properties and reduced susceptibility to chemical/thermal denaturation. Furthermore, the same conjugation protocols used to bind biomolecules to gold colloid are easily modified for nanoshells. We first review the synthesis of gold nanoshells and illustrate how the core/shell ratio and overall size of a nanoshell influences its scattering and absorption properties. We then describe several examples of nanoshell-based diagnostic and therapeutic approaches including the development of nanoshell bioconjugates for molecular imaging, the use of scattering nanoshells as contrast agents for optical coherence tomography (OCT), and the use of absorbing nanoshells in NIR thermal therapy of tumors.

Authors
Lin, AWH; Loo, CH; Hirsch, LR; Barton, JK; Lee, M-H; Halas, NJ; West, JL; Drezek, RA
MLA Citation
Lin, AWH, Loo, CH, Hirsch, LR, Barton, JK, Lee, M-H, Halas, NJ, West, JL, and Drezek, RA. "Nanoshells for integrated diagnosis and therapy of cancer." Proceedings of SPIE - The International Society for Optical Engineering 5593 (2004): 308-316.
Source
scival
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
5593
Publish Date
2004
Start Page
308
End Page
316
DOI
10.1117/12.570267

Enhancing mechanical properties of tissue engineered constructs through increased crosslinking of extracellular matrix proteins

The effect of increased expression of lysyl oxidase (LO), an enzyme involved in crosslinking extracellular matrix (ECM) proteins, on the mechanical integrity of ECM by virtually transfecting vascular smooth muscle cells (VSMCs) with LO gene, was investigated. It was observed that the elastic modulus of gels seeded with LO-transfected cells increased by almost 2-folds as compared with mock-seeded gels. It was also observed that ultimate tensile strength increases by almost 2-folds. The results show that increased mechanical strength can be achieved by increased expression of lysyl oxidase by VSMCs.

Authors
Lau, I; Starcher, B; West, JL
MLA Citation
Lau, I, Starcher, B, and West, JL. "Enhancing mechanical properties of tissue engineered constructs through increased crosslinking of extracellular matrix proteins." Transactions - 7th World Biomaterials Congress (2004): 258--.
Source
scival
Published In
Transactions - 7th World Biomaterials Congress
Publish Date
2004
Start Page
258-

Photothermal tumor therapy using metal nanoshells

A minimally, invasive photothermal cancer therapy using metal nanoshells was discussed. Nanoshells, consisting of a silica core surrounded by a thin gold shell, were new class of nanoparticle with an optical tunability that cover the visible to the near infrared (NIR) region. Complete weakening of tumors was observed in animals receiving systematic injections of nanoshells before NIR laser treatment. The results show that the systematic delivery of nanoshells in vivo provide sufficient tumor accumulation for selective heating and complete ablation of tumors, producing 100% cure rates.

Authors
Lowery, A; O'Neal, P; Hirsch, L; Halas, N; West, J
MLA Citation
Lowery, A, O'Neal, P, Hirsch, L, Halas, N, and West, J. "Photothermal tumor therapy using metal nanoshells." Transactions - 7th World Biomaterials Congress (2004): 694--.
Source
scival
Published In
Transactions - 7th World Biomaterials Congress
Publish Date
2004
Start Page
694-

Poly(ethylene glycol)-based copolymers for local delivery of nitric oxide

Poly(ethylene glycol)-based copolymers were synthesized for local delivery of nitric oxide (NO). Dendrimers were formed using liquid phase peptide synthesis. NO release from each generation of dendrimer species was determined by incubating dendrimers under physiological conditions and monitoring NO release by the Griess assay. The coupling of lysine to the dendrimer cores was monitored by Ninhydrin assay and exceeded 80%. The results confirm the ability of these materials in delivering therapeutic doses of NO to physiological systems.

Authors
Taite, LJ; Lipke, EA; West, JL
MLA Citation
Taite, LJ, Lipke, EA, and West, JL. "Poly(ethylene glycol)-based copolymers for local delivery of nitric oxide." Transactions - 7th World Biomaterials Congress (2004): 250--.
Source
scival
Published In
Transactions - 7th World Biomaterials Congress
Publish Date
2004
Start Page
250-

Nanoshells as near infrared absorbers to enhance laser tissue welding

The use of nanoshells as a exogenous near infrared (NIR) absorber in a tissue solder formulation for laser tissue welding was discussed. Mechanical testing analysis of nanoshell solder welds in muscles revealed successful fusion of tissues with tensile strength of the weld site equal to the native tissue. It was found that for a particular angle and power density there was an increase in weld strength with increase BSA concentration. It was also observed that as the angle was changed from 90° to 60° there were a significant increase in the weld strength.

Authors
Gobin, A; O'Neal, DP; Halas, NJ; West, J
MLA Citation
Gobin, A, O'Neal, DP, Halas, NJ, and West, J. "Nanoshells as near infrared absorbers to enhance laser tissue welding." Transactions - 7th World Biomaterials Congress (2004): 131--.
Source
scival
Published In
Transactions - 7th World Biomaterials Congress
Publish Date
2004
Start Page
131-

Hydrogel scaffolds with immobilized bFGF: Effects on SMCs

To optimize tissue formation, we propose the use of polyethylene glycol (PEG) conjugated growth factors that can be covalently immobilized to scaffolds. In this study, hydrogel scaffolds were modified with basic fibroblast growth factor (bFGF), which is a potent mitogen for many cell types. We have demonstrated that bFGF retains its activity following attachment to PEG and following covalent incorporation into photopolymerized hydrogel scaffolds. Further, an immobilized gradient of bFGF was formed in hydrogels, causing cells to align in the direction of increasing bFGF content.

Authors
DeLong, SD; West, JL
MLA Citation
DeLong, SD, and West, JL. "Hydrogel scaffolds with immobilized bFGF: Effects on SMCs." Transactions - 7th World Biomaterials Congress (2004): 155--.
Source
scival
Published In
Transactions - 7th World Biomaterials Congress
Publish Date
2004
Start Page
155-

Neutrophil interaction with distinct moeties in biomimetic hydrogels

The focus of this study is to use tissue-engineering methods to evaluate the mechanics of the neutrophil interactions with the extracellular matrix. Specifically, we use a (poly)ethylene glycol (PEG) polymer to form a polymerized hydrogel that serves as a biologically inert surface. By grafting bioactive moieties onto the PEG chain, the hydrogel is made bioactive. The moeties incorporated into the hydrogel are adhesive peptides that are known to interact with receptors on the surface of the neutrophil. The goal of this work is to define the mechanisms by which these engineered elements influence the interactions of neutrophils with this biomaterial. The overall goal of this work is to define the mechanisms by which these engineered elements influence the interactions of neutrophils with this clinically useful biomaterial. The current experiments analyze the interactions of isolated human neutrophils with PEG hydrogels with incorporated arginine-glycine-aspartic acid-serine, RGDS, a known peptide ligand for some β1 and β3 integrins, and threonin-methionine- lysine-isoleucine-isoleucine-proline-phynalanine-asparaginearginine-leucine- threonine-isoleucine-glycine-glycine, TMKIIPFNRLTIGG, a peptide ligand for one member of the β2 integrin family (CD11b/CD18, Mac-1). Our results demonstrate that neutrophils, with or without chemotactic stimulation, show little ability to adhere to PEG hydrogels without incorporated peptides. Incorporating distinct bioactive peptides either alone or in combination has enabled recognition of differential functions of αvβ3, β1 and β2 integrins on cell adhesion, spreading and locomotion. Combined interactions result in activity that differs markedly from that seen with either integrin independently engaged. This experimental model not only allows investigation of leukocyte functions induced through interactions with isolated, defined ligands but allows the development of engineered matrices with defined bioactive properties regarding aspects of innate immunity.

Authors
Gonzalez, AG; Gobin, A; West, J; McIntire, LV; Smith, CW
MLA Citation
Gonzalez, AG, Gobin, A, West, J, McIntire, LV, and Smith, CW. "Neutrophil interaction with distinct moeties in biomimetic hydrogels." Transactions - 7th World Biomaterials Congress (2004): 1195--.
Source
scival
Published In
Transactions - 7th World Biomaterials Congress
Publish Date
2004
Start Page
1195-

VEGF-transfected vascular smooth muscle cells promote endothelialization and capillary formation

The genetic modification of vascular smooth muscle cells (VSMC) to produce vascular endothelial growth factor (VEGF) was analyzed. VSMCs were isolated from the thoracic aorate of adult sprague-dawley rats and transfected with a retrovirus that encodes VEGF or green fluorescent protein (GFP). VSMCs were seeded into 6-well at 25×10 3 cells/cm 2 and allowed to adhere overnight. The results show that seeding of VEGF-transfected SMCs onto the luminal surface of small-diameter TEVGs may promote spontaneous endothelializarion thereby improving the patency rate of the graft.

Authors
Elbjeirami, W; West, JL
MLA Citation
Elbjeirami, W, and West, JL. "VEGF-transfected vascular smooth muscle cells promote endothelialization and capillary formation." Transactions - 7th World Biomaterials Congress (2004): 1723--.
Source
scival
Published In
Transactions - 7th World Biomaterials Congress
Publish Date
2004
Start Page
1723-

A collagen-based gene delivery system with polyethylenimine-DNA complexes

A gene delivery system was developed by embedding polyethyleimine-DNA (PEI-DNA) complexes into cell-seeded collagen gels. The main objective of the development was to enhance endothelialization of tissue engineered vascular grafts (TEVG). PEI solution was added dropwise to DNA at a molar ratio of 7.5:1. A prolonged delivery period of one month was achieved by our gene delivery system. The amount of vascular endothelial growth factor (VEGF) obtained was effective on stimulating profliferation of endothelial cells (EC).

Authors
Lau, I; West, JL
MLA Citation
Lau, I, and West, JL. "A collagen-based gene delivery system with polyethylenimine-DNA complexes." Transactions - 7th World Biomaterials Congress (2004): 660--.
Source
scival
Published In
Transactions - 7th World Biomaterials Congress
Publish Date
2004
Start Page
660-

Development of new bioengineering curricula at Rice university

Rice University has developed a new bioengineering curricula at the graduate and undergraduate levels. The new curricula aims to provide students with a rigorous engineering background while making them fully conversant in modern cellular and molecular biology. The undergarduate course includes introduction to bioengineering, MatLAb, and projects on careers in bioengineering and design principles as well as requires laboratory training. The graduate curriculum combines core coursework for all bioengineering students with track coursework for further specialization.

Authors
West, JL; Saterbak, A; San, KY
MLA Citation
West, JL, Saterbak, A, and San, KY. "Development of new bioengineering curricula at Rice university." Transactions - 7th World Biomaterials Congress (2004): 581--.
Source
scival
Published In
Transactions - 7th World Biomaterials Congress
Publish Date
2004
Start Page
581-

Molecular imaging of cancer using gold nanoshells

The use of gold nanoshells for the molecular imaging of breast cancer was discussed. The detection of the Her-2/neu receptors expressed on the cell membrane was also discussed. The formation of gold nanoshells was analyzed with a UV-Vis spectrophotometer and scanning electron microscopy. The sample nanoshells has a silica core diameter of 240 nm with a 35 nm gold shell. Scattering-based optical imaging modalities, coupled with targeted optical contrast agents, offer a new approach to clinical cancer imaging.

Authors
Loo, CH; Hirsch, LR; Halas, NJ; West, JL; Drezek, RA
MLA Citation
Loo, CH, Hirsch, LR, Halas, NJ, West, JL, and Drezek, RA. "Molecular imaging of cancer using gold nanoshells." Transactions - 7th World Biomaterials Congress (2004): 406--.
Source
scival
Published In
Transactions - 7th World Biomaterials Congress
Publish Date
2004
Start Page
406-

Nanoshell bioconjugates for integrated imaging and therapy of cancer

Currently, separate diagnostic and therapeutic modalities are required for the diagnosis and treatment of cancer. In many cases, the present standard of care requires invasive surgical procedures and/or other treatments associated with significant side effect profiles, high cost, and poor clinical outcome. A single technology with dual diagnostic/therapeutic capabilities would potentially yield significant savings in the time and cost associated with diagnosing and treating many cancers. In this paper, we discuss gold nanoshell bioconjugates and their role in the development of an integrated cancer imaging and therapy application. Nanoshells are a novel class of nanomaterials that have unique properties including continuous and broad wavelength tunability, far greater scattering and absorption coefficients, increased chemical stability, and improved biocompatibility. Here, we describe the development of an integrated cancer imaging and therapy application using near-infrared (NIR) gold nanoshell bioconjugates.

Authors
Loo, CH; Lee, M-H; Hirsch, LR; West, JL; Halas, NJ; Drezek, RA
MLA Citation
Loo, CH, Lee, M-H, Hirsch, LR, West, JL, Halas, NJ, and Drezek, RA. "Nanoshell bioconjugates for integrated imaging and therapy of cancer." Proceedings of SPIE - The International Society for Optical Engineering 5327 (2004): 1-4.
Source
scival
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
5327
Publish Date
2004
Start Page
1
End Page
4
DOI
10.1117/12.553184

Bioactive microporous PEG/YIGSR polyurethaneureas for use as small diameter vascular grafts

The development of a YIGSR peptide- and PEG-modified polyurethaneurea by incorporating YIGSR peptide sequences as a chain extender and PEG as a soft segment was studied. Bovine aortic endothelial cells (BAEC) were seeded on polymer films to evaluate biological performance. Collagen I and polyurethaneurea films were incubated with mepacrine-labeled whole blood at 25°C to evaluate platelet adhesion. Using gas foaming and salt leaching via incorporation of sodium bicarbonate, scaffolds were fabricated. It was observed that the number of cells that migrated through the PUUYIGSR-PEG matrices was significantly greater than for PEG-containing polyurethane urea (PUUPPD-PEG).

Authors
Jun, H-W; West, JL
MLA Citation
Jun, H-W, and West, JL. "Bioactive microporous PEG/YIGSR polyurethaneureas for use as small diameter vascular grafts." Transactions - 7th World Biomaterials Congress (2004): 709--.
Source
scival
Published In
Transactions - 7th World Biomaterials Congress
Publish Date
2004
Start Page
709-

Nanoshells as an optical coherence tomography contrast agent

Nanoshells are a layered dielectric core/metal shell composite nanostructure with an optical resonance geometrically tunable through the visible and near infrared. Due to their small size, ability to generate a strong backscattering signal, and potential for surface modification, they may be an ideal in vivo optical coherence tomography contrast agent. We performed a pilot study to assess their capabilities. Images of a cuvette filled with dilute nanoshells, 2 μm polystyrene microspheres, or a combination were obtained. When compared to microspheres, images of the nanoshells where much brighter and attenuation of the bottom cuvette interface less. Injection of micropheres into the tail vein of mice and hamsters caused a noticeable brightening of OCT images of the dorsal skin. These pilot studies indicate that nanoshells may be an excellent OCT contrast agent; work is continuing to determine optimum nanoshell parameters and applications.

Authors
Barton, JK; Halas, NJ; West, JL; Drezek, RA
MLA Citation
Barton, JK, Halas, NJ, West, JL, and Drezek, RA. "Nanoshells as an optical coherence tomography contrast agent." Proceedings of SPIE - The International Society for Optical Engineering 5316 (2004): 99-106.
Source
scival
Published In
Proceedings of SPIE - The International Society for Optical Engineering
Volume
5316
Publish Date
2004
Start Page
99
End Page
106
DOI
10.1117/12.529235

Development of a YIGSR-peptide-modified polyurethaneurea to enhance endothelialization

Polyurethanes have been investigated for use as vascular grafts due to their excellent mechanical properties and relatively good biocompatibility. However, poor retention of endothelial cells and thrombogenicity in vivo remain problematic for vascular graft applications. The peptide YIGSR has been shown to increase endothelial cell adhesion but not attachment of platelets, suggesting its possible utility for vascular graft applications. In this study, a bioactive polyurethaneurea has been synthesized by incorporating GGGYIGSRGGGK peptide sequences into the polymer backbone. Successful incorporation of the peptides was confirmed by NMR, contact angle measurement and ESCA. Uniform distribution of peptides on the surface was observed using a fluorescent probe capable of reacting with tyrosine residues on the peptides. Hard segment domains were visualized using tapping mode AFM. Endothelial cell adhesion, spreading, proliferation, migration and extra-cellular matrix production were improved on bioactive polyurethaneurea compared to control polyurethaneurea. Competitive inhibition of endothelial cell attachment and spreading by soluble YIGSR peptides indicated that cell adhesion and spreading were specifically mediated by YIGSR-sensitive cell adhesion receptor, not just by changed surface properties. There was no significant difference in the number of adherent platelets. Therefore, this bioactive polyurethanurea may improve vascular graft endothelialization without increasing thrombogenicity.

Authors
Jun, H-W; West, J
MLA Citation
Jun, H-W, and West, J. "Development of a YIGSR-peptide-modified polyurethaneurea to enhance endothelialization." Journal of Biomaterials Science, Polymer Edition 15.1 (2004): 73-94.
PMID
15027844
Source
scival
Published In
Journal of Biomaterials Science, Polymer Edition
Volume
15
Issue
1
Publish Date
2004
Start Page
73
End Page
94
DOI
10.1163/156856204322752246

Modification of materials with bioactive peptides.

Authors
West, JL
MLA Citation
West, JL. "Modification of materials with bioactive peptides." Methods in molecular biology (Clifton, N.J.) 238 (2004): 113-122.
PMID
14970442
Source
scival
Published In
Methods in molecular biology (Clifton, N.J.)
Volume
238
Publish Date
2004
Start Page
113
End Page
122

Drug delivery - Pulsed polymers

Authors
West, JL
MLA Citation
West, JL. "Drug delivery - Pulsed polymers." NATURE MATERIALS 2.11 (November 2003): 709-710. (Academic Article)
Source
manual
Published In
Nature Materials
Volume
2
Issue
11
Publish Date
2003
Start Page
709
End Page
710
DOI
10.1038/nmat1005

Nitric oxide-generating hydrogels inhibit neointimal formation

Authors
Lipke, EA; Masters, KS; Myler, HA; West, JL
MLA Citation
Lipke, EA, Masters, KS, Myler, HA, and West, JL. "Nitric oxide-generating hydrogels inhibit neointimal formation." CIRCULATION 108.17 (October 2003): 353-353. (Academic Article)
Source
manual
Published In
Circulation
Volume
108
Issue
17
Publish Date
2003
Start Page
353
End Page
353

Val-ala-pro-gly, an elastin-derived non-integrin ligand: Smooth muscle cell adhesion and specificity

The elastin-derived peptide val-ala-pro-gly (VAPG) may be useful as a biospecific cell adhesion ligand for smooth muscle cells. By grafting the peptide sequence into a hydrogel material, we were able to assess its effects on smooth muscle cell adhesion and spreading. These materials are photopolymerizable hydrogels based on acrylate-terminated derivatives of polyethylene glycol (PEG). Because of their high PEG content, these materials are highly resistant to protein adsorption and cell adhesion. However, PEG diacrylate derivatives can be mixed with adhesive peptide-modified PEG monoacrylate derivatives to facilitate cell adhesion. Following photopolymerization, PEG monoacrylate derivatives are grafted into the hydrogel network formed by the PEG diacrylate. This results in covalent immobilization of adhesive peptides to the hydrogel via a flexible linker chain. The resistance of PEG to protein adsorption makes it an ideal material for this model system since cell-material interactions are limited to biomolecules that are covalently incorporated into the material. In this case we were able to demonstrate that VAPG is specific for adhesion of smooth muscle cells. It also was shown that fibroblasts, endothelial cells, and platelets cannot adhere to VAPG. In addition, not only was smooth muscle cell adhesion dependent on ligand concentration, but also cell spreading increased with increasing ligand concentration. (C) 2003 Wiley Periodicals, Inc.

Authors
Gobin, AS; West, JL
MLA Citation
Gobin, AS, and West, JL. "Val-ala-pro-gly, an elastin-derived non-integrin ligand: Smooth muscle cell adhesion and specificity." JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 67A.1 (October 2003): 255-259. (Academic Article)
Source
manual
Published In
Journal of Biomedical Materials Research
Volume
67A
Issue
1
Publish Date
2003
Start Page
255
End Page
259
DOI
10.1002/jbm.a.10110

Enhancing mechanical properties of tissue-engineered constructs via lysyl oxidase crosslinking activity

A number of strategies have been investigated to enhance the mechanical stability of engineered tissues. In this study, we utilized lysyl oxidase (LO) to enzymatically crosslink extracellular matrix (ECM) proteins, particularly collagen and elastin, to enhance the mechanical integrity of the ECM and thereby impart mechanical strength to the engineered tissue. Vascular smooth muscle cells (VSMCs) were liposomally transfected with the LO gene. Both Northern and Wester analyses confirmed increased LO expression. Increased LO activity was demonstrated using a fluorescent enzyme substrate assay and by observation of the presence of increased levels of desmosine, a product of LO crosslinking, in the ECM. The mechanical effects of altered crosslink densities within tissue-engineered constructs were demonstrated in a VSMC-populated collagen gel model. When smooth muscle cells transfected with lysyl oxidase were seeded in collagen gels, the tensile strength and elastic modulus in these constructs increased by approximately two-fold compared to constructs seeded with mock-transfected VSMCs. Also, desmosine levels in the LO-populated collagen gels were higher than they were in mock-seeded gels, as demonstrated via immunohistochernical staining. Compositional analysis of the ECM deposited by the transformed cells showed similar collagen and elastin levels, and cell proliferation rates were similar as well, thus attributing increased mechanical properties to ECM crosslinking.

Authors
Elbjeirami, WM; Yonter, EO; Starcher, BC; West, JL
MLA Citation
Elbjeirami, WM, Yonter, EO, Starcher, BC, and West, JL. "Enhancing mechanical properties of tissue-engineered constructs via lysyl oxidase crosslinking activity." JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A 66A.3 (September 2003): 513-521. (Academic Article)
Source
manual
Published In
Journal of Biomedical Materials Research
Volume
66A
Issue
3
Publish Date
2003
Start Page
513
End Page
521
DOI
10.1002/jbm.a.10021

Optically-responsive nanoshell composites.

Authors
West, JL; Halas, N; Sershen, SR
MLA Citation
West, JL, Halas, N, and Sershen, SR. "Optically-responsive nanoshell composites." ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 225 (March 2003): U522-U522. (Academic Article)
Source
manual
Published In
ACS National Meeting Book of Abstracts
Volume
225
Publish Date
2003
Start Page
U522
End Page
U522

Engineered nanomaterials for biophotonics applications: Improving sensing, imaging, and therapeutics

Advances in chemistry and physics are providing an expanding array of nanostructured materials with unique and powerful optical properties. These nanomaterials provide a new set of tools that are available to biomedical engineers, biologists, and medical scientists who seek new tools as biosensors and probes of biological fluids, cells, and tissue chemistry and function. Nanomaterials are also being used to develop optically controlled devices for applications such as modulated drug delivery as well as optical therapeutics. This review discusses applications that have been successfully demonstrated using nanomaterials including semiconductor nanocrystals, gold nanoparticles, gold nanoshells, and silver plasmon resonant particles.

Authors
West, JL; Halas, NJ
MLA Citation
West, JL, and Halas, NJ. "Engineered nanomaterials for biophotonics applications: Improving sensing, imaging, and therapeutics." Annual Review of Biomedical Engineering 5 (2003): 285-292.
PMID
14527314
Source
scival
Published In
Annual Review of Biomedical Engineering
Volume
5
Publish Date
2003
Start Page
285
End Page
292
DOI
10.1146/annurev.bioeng.5.011303.120723

Effects of Epidermal Growth Factor on Fibroblast Migration through Biomimetic Hydrogels

We have previously reported on the development and use of synthetic hydrogel extracellular matrix (ECM) analogues that can be used to study the mechanisms of migration. These biomimetic hydrogels consist of bioinert poly(ethylene glycol) diacrylate derivatives with proteolytically degradable peptide sequences included in the backbone of the polymer and adhesion peptide sequences grafted into the network. Cells adhere to the hydrogel via interaction between the grafted adhesion ligands and receptors on the cell surface. The cells migrate through the three-dimensional system by secreting the appropriate proteolytic enzymes, which are involved in cell migration and are targeted to the peptide sequences incorporated in the backbone of the polymer. It was observed that cell migration has a biphasic dependence on adhesion ligand concentration, with optimal migration at intermediate ligand levels. In this study, we demonstrate that we can covalently attach epidermal growth factor (EGF) to PEG and graft them into the hydrogels. It was observed that EGF when tethered maintained mitogenic activity. It was also observed that fibroblast migration significantly increased in the presence of the grafted EGF through the collagenase-sensitive hydrogels. In addition, the increase in migration was found to be independent from the proliferative response of the cells. These synthetic ECM analogues allow one to systematically control identities and concentrations of biomolecules and are useful tools to study mechanisms of cell migration.

Authors
Gobin, AS; West, JL
MLA Citation
Gobin, AS, and West, JL. "Effects of Epidermal Growth Factor on Fibroblast Migration through Biomimetic Hydrogels." Biotechnology Progress 19.6 (2003): 1781-1785.
PMID
14656156
Source
scival
Published In
Biotechnology Progress
Volume
19
Issue
6
Publish Date
2003
Start Page
1781
End Page
1785
DOI
10.1021/bp0341390

Tissue engineered small-diameter vascular grafts

Arterial occlusive disease remains the leading cause of death in western countries and often requires vascular reconstructive surgery. The limited supply of suitable small-diameter vascular grafts has led to the development of tissue engineered blood vessel substitutes. Many different approaches have been examined, including natural scaffolds containing one or more ECM proteins and degradable polymeric scaffolds. For optimal graft development, many efforts have modified the culture environment to enhance ECM synthesis and organization using bioreactors under physiologic conditions and biochemical supplements. In the past couple of decades, a great deal of progress on TEVGs has been made. Many challenges remain and are being addressed, particularly with regard to the prevention of thrombosis and the improvement of graft mechanical properties. To develop a patent TEVG that grossly resembles native tissue, required culture times in most studies exceed 8 weeks. Even with further advances in the field, TEVGs will likely not be used in emergency situations because of the time necessary to allow for cell expansion, ECM production and organization, and attainment of desired mechanical strength. Furthermore, TEVGs will probably require the use of autologous tissue to prevent an immunogenic response, unless advances in immune acceptance render allogenic and xenogenic tissue use feasible. TEVGs have not yet been subjected to clinical trials, which will determine the efficacy of such grafts in the long term. Finally, off-the-shelf availability and cost will become the biggest hurdles in the development of a feasible TEVG product. Although many obstacles exist in the effort to develop a small-diameter TEVG, the potential benefits of such an achievement are exciting. In the near future, a nonthrombogenic TEVG with sufficient mechanical strength may be developed for clinical trials. Such a graft will have the minimum characteristics of biological tissue necessary to remain patent over a period comparable to current vein graft therapies. As science and technology advance, TEVGs may evolve into complex blood vessel substitutes. TEVGs may become living grafts, capable of growing, remodeling, and responding to mechanical and biochemical stimuli in the surrounding environment. These blood vessel substitutes will closely resemble native vessels in almost every way, including structure, composition, mechanical properties, and function. They will possess vasoactive properties and be able to dilate and constrict in response to stimuli. Close mimicry of native blood vessels may aid in the engineering of other tissues dependent upon vasculature to sustain function. With further understanding of the factors involved in cardiovascular development and function combined with the foundation of knowledge already in place, the development of TEVGs should one day lead to improved quality of life for those with vascular disease and other life-threatening conditions.

Authors
Schmedlen, RH; Elbjeirami, WM; Gobin, AS; West, JL
MLA Citation
Schmedlen, RH, Elbjeirami, WM, Gobin, AS, and West, JL. "Tissue engineered small-diameter vascular grafts." Clinics in Plastic Surgery 30.4 (2003): 507-517.
PMID
14621299
Source
scival
Published In
Clinics in Plastic Surgery
Volume
30
Issue
4
Publish Date
2003
Start Page
507
End Page
517
DOI
10.1016/S0094-1298(03)00069-5

Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance

Metal nanoshells are a class of nanoparticles with tunable optical resonances. In this article, an application of this technology to thermal ablative therapy for cancer is described. By tuning the nanoshells to strongly absorb light in the near infrared, where optical transmission through tissue is optimal, a distribution of nanoshells at depth in tissue can be used to deliver a therapeutic dose of heat by using moderately low exposures of extracorporeally applied near-infrared (NIR) light. Human breast carcinoma cells incubated with nanoshells in vitro were found to have undergone photothermally induced morbidity on exposure to NIR light (820 nm, 35 W/cm 2), as determined by using a fluorescent viability stain. Cells without nanoshells displayed no loss in viability after the same periods and conditions of NIR illumination. Likewise, in vivo studies under magnetic resonance guidance revealed that exposure to low doses of NIR light (820 nm, 4 W/cm2) in solid tumors treated with metal nanoshells reached average maximum temperatures capable of inducing irreversible tissue damage (ΔT = 37.4 ± 6.6°C) within 4-6 min. Controls treated without nanoshells demonstrated significantly lower average temperatures on exposure to NIR light (ΔT < 10°C). These findings demonstrated good correlation with histological findings. Tissues heated above the thermal damage threshold displayed coagulation, cell shrinkage, and loss of nuclear staining, which are indicators of irreversible thermal damage. Control tissues appeared undamaged.

Authors
Hirsch, LR; Stafford, RJ; Bankson, JA; Sershen, SR; Rivera, B; Price, RE; Hazle, JD; Halas, NJ; West, JL
MLA Citation
Hirsch, LR, Stafford, RJ, Bankson, JA, Sershen, SR, Rivera, B, Price, RE, Hazle, JD, Halas, NJ, and West, JL. "Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance." Proceedings of the National Academy of Sciences of the United States of America 100.23 (2003): 13549-13554.
PMID
14597719
Source
scival
Published In
Proceedings of the National Academy of Sciences of the United States of America
Volume
100
Issue
23
Publish Date
2003
Start Page
13549
End Page
13554
DOI
10.1073/pnas.2232479100

Controlling the surface enhanced Raman effect via the nanoshell geometry

The variation of the core diameter and shell layer thicknesses of a metal nanoshell, tuning the local surface electromagnetic field of the nanoparticle in a controlled manner, was studied. The electromagnetic field at the surface of the nanoparticle was monitored as a function of the nanoparticle's core and shell dimensions. The results showed that the core shell topology provided a useful topology for manipulation of electromagnetic fields at nanoscale dimensions in a controlled manner.

Authors
Jackson, JB; Westcott, SL; Hirsch, LR; West, JL; Halas, NJ
MLA Citation
Jackson, JB, Westcott, SL, Hirsch, LR, West, JL, and Halas, NJ. "Controlling the surface enhanced Raman effect via the nanoshell geometry." Applied Physics Letters 82.2 (2003): 257-259.
Source
scival
Published In
Applied Physics Letters
Volume
82
Issue
2
Publish Date
2003
Start Page
257
End Page
259
DOI
10.1063/1.1534916

Val-ala-pro-gly, an elastin-derived non-integrin ligand: Smooth muscle cell adhesion and specificity

The elastin-derived peptide val-ala-pro-gly (VAPG) may be useful as a biospecific cell adhesion ligand for smooth muscle cells. By grafting the peptide sequence into a hydrogel material, we were able to assess its effects on smooth muscle cell adhesion and spreading. These materials are photopolymerizable hydrogels based on acrylate-terminated derivatives of polyethylene glycol (PEG). Because of their high PEG content, these materials are highly resistant to protein adsorption and cell adhesion. However, PEG diacrylate derivatives can be mixed with adhesive peptide-modified PEG monoacrylate derivatives to facilitate cell adhesion. Following photopolymerization, PEG monoacrylate derivatives are grafted into the hydrogel network formed by the PEG diacrylate. This results in covalent immobilization of adhesive peptides to the hydrogel via a flexible linker chain. The resistance of PEG to protein adsorption makes it an ideal material for this model system since cell-material interactions are limited to biomolecules that are covalently incorporated into the material. In this case we were able to demonstrate that VAPG is specific for adhesion of smooth muscle cells. It also was shown that fibroblasts, endothelial cells, and platelets cannot adhere to VAPG. In addition, not only was smooth muscle cell adhesion dependent on ligand concentration, but also cell spreading increased with increasing ligand concentration. © 2003 Wiley Periodicals, Inc.

Authors
Gobin, AS; West, JL
MLA Citation
Gobin, AS, and West, JL. "Val-ala-pro-gly, an elastin-derived non-integrin ligand: Smooth muscle cell adhesion and specificity." Journal of Biomedical Materials Research - Part A 67.1 (2003): 255-259.
PMID
14517884
Source
scival
Published In
Journal of Biomedical Materials Research - Part A
Volume
67
Issue
1
Publish Date
2003
Start Page
255
End Page
259

Enhancing mechanical properties of tissue-engineered constructs via lysyl oxidase crosslinking activity

A number of strategies have been investigated to enhance the mechanical stability of engineered tissues. In this study, we utilized lysyl oxidase (LO) to enzymatically crosslink extracellular matrix (ECM) proteins, particularly collagen and elastin, to enhance the mechanical integrity of the ECM and thereby impart mechanical strength to the engineered tissue. Vascular smooth muscle cells (VSMCs) were liposomally transfected with the LO gene. Both Northern and Western analyses confirmed increased LO expression. Increased LO activity was demonstrated using a fluorescent enzyme substrate assay and by observation of the presence of increased levels of desmosine, a product of LO crosslinking, in the ECM. The mechanical effects of altered crosslink densities within tissue-engineered constructs were demonstrated in a VSMC-populated collagen gel model. When smooth muscle cells transfected with lysyl oxidase were seeded in collagen gels, the tensile strength and elastic modulus in these constructs increased by approximately two-fold compared to constructs seeded with mock-transfected VSMCs. Also, desmosine levels in the LO-populated collagen gels were higher than they were in mock-seeded gels, as demonstrated via immunohistochemical staining. Compositional analysis of the ECM deposited by the transformed cells showed similar collagen and elastin levels, and cell proliferation rates were similar as well, thus attributing increased mechanical properties to ECM crosslinking. © 2003 Wiley Periodicals, Inc.

Authors
Elbjeirami, WM; Yonter, EO; Starcher, BC; West, JL
MLA Citation
Elbjeirami, WM, Yonter, EO, Starcher, BC, and West, JL. "Enhancing mechanical properties of tissue-engineered constructs via lysyl oxidase crosslinking activity." Journal of Biomedical Materials Research - Part A 66.3 (2003): 513-521.
PMID
12918034
Source
scival
Published In
Journal of Biomedical Materials Research - Part A
Volume
66
Issue
3
Publish Date
2003
Start Page
513
End Page
521

A whole blood immunoassay using gold nanoshells

A rapid immunoassay capable of detecting analyte within complex biological media without any sample preparation is described. This was accomplished using gold nanoshells, layered dielectric-metal nanoparticles whose optical resonance is a function of the relative size of its constituent layers. Aggregation of antibody/nanoshell conjugates with extinction spectra in the near-infrared was monitored spectroscopically in the presence of analyte. Successful detection of immunoglobulins was achieved in saline, serum, and whole blood. This system constitutes a simple immunoassay capable of detecting sub-nanogram-permilliliter quantities of various analytes in different media within 10-30 min.

Authors
Hirsch, LR; Jackson, JB; Lee, A; Halas, NJ; West, JL
MLA Citation
Hirsch, LR, Jackson, JB, Lee, A, Halas, NJ, and West, JL. "A whole blood immunoassay using gold nanoshells." Analytical Chemistry 75.10 (2003): 2377-2381.
PMID
12918980
Source
scival
Published In
Analytical Chemistry
Volume
75
Issue
10
Publish Date
2003
Start Page
2377
End Page
2381
DOI
10.1021/ac0262210

Erratum: Implantable, polymeric systems for modulated drug delivery (Advanced Drug Delivery Reviews (2002) 54 (1225-1235) PII: S0169409X0200090X)

Authors
Sershen, S; West, J
MLA Citation
Sershen, S, and West, J. "Erratum: Implantable, polymeric systems for modulated drug delivery (Advanced Drug Delivery Reviews (2002) 54 (1225-1235) PII: S0169409X0200090X)." Advanced Drug Delivery Reviews 55.3 (2003): 439--.
Source
scival
Published In
Advanced Drug Delivery Reviews
Volume
55
Issue
3
Publish Date
2003
Start Page
439-
DOI
10.1016/S0169-409X(02)00265-X

A Rapid, Whole Blood Immunoassay using Metal Nanoshells

Using metal nanoshells as an immunoassay substrate, we describe an immunoassay capable of detecting blood borne analyte on the order of minutes. Near infrared resonant gold nanoshells were labeled with antibodies specific to rabbit IgG analyte. The antibody-nanoshell conjugates were detectable via near infrared photometry in solution with saline, serum, and whole blood. Addition of analyte induced aggregation of antibody-nanoshell conjugates, causing a decrease in the original nanoshell near infrared resonance. Aggregation proceeded in a concentration dependent fasion in all three mediums (saline, serum, whole blood), permitting quantitative detection of analyte within 10 - 30 minutes and sensitivities < 1 ng/mL.

Authors
Hirsch, LR; West, JL; Jackson, JB; Lee, A; Halas, NJ
MLA Citation
Hirsch, LR, West, JL, Jackson, JB, Lee, A, and Halas, NJ. "A Rapid, Whole Blood Immunoassay using Metal Nanoshells." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 4 (2003): 3442-3443.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
4
Publish Date
2003
Start Page
3442
End Page
3443

Nanoshell-Mediated Near Infrared Photothermal Tumor Therapy

A novel photothermal therapy of neoplastic tissue is described. The use of near infrared (NIR) absorbing nanoshells permits targeted photothermal ablation of tumor tissue via NIR heating of nanoshell-laden tumors using an extracorporeal near infrared source. Human breast carcinoma cells incubated with nanoshells in vitro were found to undergo photothermally induced morbitity upon exposure to NIR light (820 nm, 44 W/cm2) as determined using a fluorescent viability stain. Cells without nanoshells displayed no loss in viability after the same periods and conditions of near infrared illumination. Likewise, in vivo studies under MR guidance revealed that exposure to low doses of near infrared light (820 nm, 4 W/cm2) in solid tumors treated with metal nanoshells reached average temperatures capable of inducing irreversible tissue damage (δT = 37.4 ± 6.6°C) within 4-6 minutes. Controls treated without nanoshells demonstrated significantly less average temperatures upon exposure to near infrared light (δT< 10°C). These findings demonstrated good correlation with histological findings. Tissues heated above the thermal damage threshold displayed coagulation, cell shrinkage, and loss of nuclear staining - indicators of irreversible thermal damage. Control tissues did not display these indicators and appeared undamaged.

Authors
Hirsch, LR; West, JL; Stafford, RJ; Bankson, JA; Sershen, SR; Price, RE; Hazle, JD; Halas, NJ
MLA Citation
Hirsch, LR, West, JL, Stafford, RJ, Bankson, JA, Sershen, SR, Price, RE, Hazle, JD, and Halas, NJ. "Nanoshell-Mediated Near Infrared Photothermal Tumor Therapy." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 2 (2003): 1230-1231.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
2
Publish Date
2003
Start Page
1230
End Page
1231

Heparanase and platelet factor-4 induce smooth muscle cell proliferation and migration via bFGF release from the ECM: Possible implications in the restenosis process

Authors
Myler, HA; West, JL
MLA Citation
Myler, HA, and West, JL. "Heparanase and platelet factor-4 induce smooth muscle cell proliferation and migration via bFGF release from the ECM: Possible implications in the restenosis process." FASEB JOURNAL 16.4 (March 2002): A91-A91. (Academic Article)
Source
manual
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
16
Issue
4
Publish Date
2002
Start Page
A91
End Page
A91

Scaffolds modified with tethered growth factors to influence smooth muscle cell behavior

Authors
DeLong, SA; Mann, BK; West, JL
MLA Citation
DeLong, SA, Mann, BK, and West, JL. "Scaffolds modified with tethered growth factors to influence smooth muscle cell behavior." FASEB JOURNAL 16.4 (March 2002): A36-A36. (Academic Article)
Source
manual
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
16
Issue
4
Publish Date
2002
Start Page
A36
End Page
A36

YC-1 attenuates neointimal formation through acute suppression of vascular SMC proliferation and platelet function

Authors
Tulis, DA; Masters, KSB; Lipke, EA; Schiesser, RL; Evans, AJ; Durante, W; West, JL; Schafer, AI
MLA Citation
Tulis, DA, Masters, KSB, Lipke, EA, Schiesser, RL, Evans, AJ, Durante, W, West, JL, and Schafer, AI. "YC-1 attenuates neointimal formation through acute suppression of vascular SMC proliferation and platelet function." FASEB JOURNAL 16.4 (March 2002): A437-A437. (Academic Article)
Source
manual
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
16
Issue
4
Publish Date
2002
Start Page
A437
End Page
A437

Tissue engineered vascular grafts: Effects of bioactive scaffolds and mechanical stimulation

Authors
West, JL
MLA Citation
West, JL. "Tissue engineered vascular grafts: Effects of bioactive scaffolds and mechanical stimulation." FASEB JOURNAL 16.5 (March 2002): A1251-A1251. (Academic Article)
Source
manual
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
16
Issue
5
Publish Date
2002
Start Page
A1251
End Page
A1251

Cell migration through defined, synthetic extracellular matrix analogues

We have developed synthetic hydrogel extracellular matrix (ECM) analogues that can be used to study mechanisms involved in cell migration, such as receptor-ligand interactions and proteolysis. The biomimetic hydrogels consist of bioinert polyethylene glycol diacrylate derivatives with proteolytically degradable peptide sequences included in the backbone of the polymer and adhesive peptide sequences grafted to the network. Hydrogels have been developed that degrade as cells secrete proteolytic enzymes. Adhesive peptide sequences grafted to the hydrogel provide ligands that can interact with receptors on the cell surface to mediate adhesion and spreading. In this study, we have characterized the effects of adhesive ligand density on fibroblast migration through collagenase-degradable and plasmin-degradable hydrogels and on smooth muscle cell migration through elastase-degradable hydrogels. In all three cases, we found that cell migration has a biphasic dependence on adhesion ligand concentration, with optimal migration at intermediate ligand levels. Furthermore, both adhesive and proteolytically degradable sequences were required for cell migration to occur. These synthetic ECM analogues may be useful for 3-D mechanistic studies of many aspects of cell migration.

Authors
Gobin, AS; West, JL
MLA Citation
Gobin, AS, and West, JL. "Cell migration through defined, synthetic extracellular matrix analogues." FASEB JOURNAL 16.3 (March 2002): 751-+. (Academic Article)
Source
manual
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
16
Issue
3
Publish Date
2002
Start Page
751
End Page
+
DOI
10.1096/fj.01-0759fje

Genetic modification of smooth muscle cells (SMCs) to enhance the performance of tissue engineered vascular grafts (TEVG)

Authors
Elbjeirami, WM; Yonter, E; Scott Burden, T; West, JL
MLA Citation
Elbjeirami, WM, Yonter, E, Scott Burden, T, and West, JL. "Genetic modification of smooth muscle cells (SMCs) to enhance the performance of tissue engineered vascular grafts (TEVG)." FASEB JOURNAL 16.4 (March 2002): A471-A472. (Academic Article)
Source
manual
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
16
Issue
4
Publish Date
2002
Start Page
A471
End Page
A472

Effects of nitric oxide releasing poly(vinyl alcohol) hydrogel dressings on dermal wound healing in diabetic mice

Healing of chronic wounds such as diabetic foot ulcers is a significant clinical problem. Methods of accelerating healing in these difficult lower extremity sites include use of growth factor-loaded gels, hyperbaric oxygen, grafts, and artificial skin replacements. Nitric oxide (NO) has been proposed as a possible active agent for enhancing wound healing. This study examines the in vitro and in vivo responses to a novel hydrogel that produces therapeutic levels of NO. A hydrogel wound dressing was fabricated using ultraviolet light-initiated polymerization from poly(vinyl alcohol) with a NO donor covalently coupled to the polymer backbone. NO release from the NO-modified hydrogel was shown to occur over a time period of up to 48 hours, and there was no associated decrease in fibroblast growth or viability in vitro associated with NO hydrogels. Fibroblasts in culture with NO hydrogels had an increased production of extracellular matrix compared with cells cultured without the NO hydrogels. Preliminary animal studies in a diabetic mouse, impaired wound healing model were conducted comparing low (0.5 mM) and high (5 mM) doses of NO. Time to complete closure was similar in control wounds and NO-treated wounds; however, at 8 days control wounds were significantly smaller than NO-treated wounds. By days 10 to 13 this delay was no longer apparent. Granulation tissue thickness within the wounds at days 8 and 15 and scar tissue thickness after wound closure were increased in animals exposed to higher dose NO hydrogels. The results of this study suggest that exogenous NO released from a hydrogel wound dressing has potential to modulate wound healing.

Authors
Masters, KSB; Leibovich, SJ; Belem, P; West, JL; Poole-Warren, LA
MLA Citation
Masters, KSB, Leibovich, SJ, Belem, P, West, JL, and Poole-Warren, LA. "Effects of nitric oxide releasing poly(vinyl alcohol) hydrogel dressings on dermal wound healing in diabetic mice." Wound Repair and Regeneration 10.5 (2002): 286-294.
PMID
12406164
Source
scival
Published In
Wound Repair and Regeneration
Volume
10
Issue
5
Publish Date
2002
Start Page
286
End Page
294
DOI
10.1046/j.1524-475X.2002.10503.x

Independent optically addressable nanoparticle-polymer optomechanical composites

We report the fabrication and characterization of optomechanically active composite materials consisting of a thermally responsive poly(NIPAAm-co-AAm) hydrogel matrix incorporating a dilute concentration of Au or silica-Au core-shell nanoparticles. Under optical illumination at the resonance absorption wavelength of the nanoparticle dopant, a dramatic volume collapse of the composite occurs due to local photothermal heating of the NIPAAm matrix. Nanoparticle dopants were chosen so that each composite was specifically optically addressable, exhibiting optomechanical behavior at independent wavelengths. Such materials can be useful as independently addressable remotely triggerable switches and gates in a wide variety of micromechanical applications. © 2002 American Institute of Physics.

Authors
Sershen, SR; Westcott, SL; Halas, NJ; West, JL
MLA Citation
Sershen, SR, Westcott, SL, Halas, NJ, and West, JL. "Independent optically addressable nanoparticle-polymer optomechanical composites." Applied Physics Letters 80.24 (2002): 4609-4611.
Source
scival
Published In
Applied Physics Letters
Volume
80
Issue
24
Publish Date
2002
Start Page
4609
End Page
4611
DOI
10.1063/1.1481536

YC-1-mediated vascular protection through inhibition of smooth muscle cell proliferation and platelet function

YC-1, a synthetic benzyl indazole derivative, is capable of stimulating endogenous vessel wall cyclic guanosine monophosphate (cGMP) production and attenuating the remodeling response to experimental arterial angioplasty. In an effort to investigate the mechanisms of this YC-1-mediated vasoprotection, we examined the influence of soluble YC-1 or YC-1 incorporated in a polyethylene glycol (PEG) hydrogel on cultured rat vascular smooth muscle cell (SMC) cGMP synthesis, SMC proliferation, and platelet function. Results demonstrate that soluble YC-1 stimulated SMC cGMP production in a dose-dependent fashion, while both soluble and hydrogel-released YC-1 inhibited vascular SMC proliferation in a dose-dependent fashion without effects on cell viability. Platelet aggregation and adherence to collagen were both significantly inhibited in a dose-dependent fashion by soluble and hydrogel-released YC-1. Arterial neointima formation following experimental balloon injury was significantly attenuated by perivascular hydrogel-released YC-1. These results suggest that YC-1 is a potent, physiologically active agent with major anti-proliferative and anti-platelet properties that may provide protection against vascular injury through cGMP-dependent mechanisms. © 2002 Elsevier Science (USA).

Authors
Tulis, DA; Masters, KSB; Lipke, EA; Schiesser, RL; Evans, AJ; Peyton, KJ; Durante, W; West, JL; Schafer, AI
MLA Citation
Tulis, DA, Masters, KSB, Lipke, EA, Schiesser, RL, Evans, AJ, Peyton, KJ, Durante, W, West, JL, and Schafer, AI. "YC-1-mediated vascular protection through inhibition of smooth muscle cell proliferation and platelet function." Biochemical and Biophysical Research Communications 291.4 (2002): 1014-1021.
PMID
11866467
Source
scival
Published In
Biochemical and Biophysical Research Communications
Volume
291
Issue
4
Publish Date
2002
Start Page
1014
End Page
1021
DOI
10.1006/bbrc.2002.6552

Photocrosslinkable polyvinyl alcohol hydrogels that can be modified with cell adhesion peptides for use in tissue engineering

Photoactive polyvinyl alcohol hydrogels (PVA) have been investigated for use as tissue engineering scaffolds. These materials allow in situ polymerization for minimally invasive implantation methods. The mechanical properties of these materials can be tailored for a variety of soft tissue applications. The Young's modulus and ultimate tensile strength of PVA hydrogels are increased with increasing polymer concentration, and highly elastic hydrogels can be formed by altering the number of crosslinkable groups per chain. Fibroblasts homogeneously seeded within 3mm thick PVA hydrogels remained viable throughout 2 weeks in culture, with no differences in viability across the thickness of the hydrogel. Cells seeded within the PVA hydrogels also produce extracellular matrix proteins, as indicated by the production of hydroxyproline during culture. Intrinsically cell non-adhesive, these PVA hydrogels were functionalized with the cell-adhesive peptide RGDS and found to support the attachment and spreading of fibroblasts in a dose-dependent manner. These results suggest that photopolymerizable PVA hydrogels are promising for tissue engineering applications. © 2002 Elsevier Science Ltd. All rights reserved.

Authors
Schmedlen, RH; Masters, KS; West, JL
MLA Citation
Schmedlen, RH, Masters, KS, and West, JL. "Photocrosslinkable polyvinyl alcohol hydrogels that can be modified with cell adhesion peptides for use in tissue engineering." Biomaterials 23.22 (2002): 4325-4332.
PMID
12219822
Source
scival
Published In
Biomaterials
Volume
23
Issue
22
Publish Date
2002
Start Page
4325
End Page
4332
DOI
10.1016/S0142-9612(02)00177-1

Cell adhesion peptides alter smooth muscle cell adhesion, proliferation, migration, and matrix protein synthesis on modified surfaces and in polymer scaffolds

The effects of cell adhesion peptides (RGDS, KQAGDV, VAPG) on vascular smooth muscle cells grown on modified surfaces and in tissue-engineering scaffolds were examined. Cells were more strongly adhered to surfaces modified with adhesive ligands than to control surfaces (no ligand or a nonadhesive ligand). Cell migration was higher on surfaces with 0.2 nmol/cm2 of adhesive ligand than on control surfaces, but it was lower on surfaces with 2.0 nmol/cm2 of adhesive ligand than it was on control surfaces. Further, cell proliferation was lower on adhesive surfaces than it was on control surfaces, and it decreased as the ligand density increased. Similarly, in the peptidegrafted hydrogel scaffolds, cell proliferation was lower in scaffolds containing the adhesive peptides than it was in control scaffolds. After 7 days of culture, more collagen per cell was produced in control scaffolds than in scaffolds containing adhesive peptides. In addition, collagen production decreased in the scaffolds as the ligand concentration increased. While modification of a surface or scaffold material with adhesive ligands initially increases cell attachment, it may be necessary to optimize cell adhesion simultaneously with proliferation, migration, and matrix production. © 2002 John Wiley & Sons, Inc.

Authors
Mann, BK; West, JL
MLA Citation
Mann, BK, and West, JL. "Cell adhesion peptides alter smooth muscle cell adhesion, proliferation, migration, and matrix protein synthesis on modified surfaces and in polymer scaffolds." Journal of Biomedical Materials Research 60.1 (2002): 86-93.
PMID
11835163
Source
scival
Published In
Journal of Biomedical Materials Research
Volume
60
Issue
1
Publish Date
2002
Start Page
86
End Page
93
DOI
10.1002/jbm.10042

Photopolymerizable hydrogels for tissue engineering applications

Photopolymerized hydrogels are being investigated for a number of tissue engineering applications because of the ability to form these materials in situ in a minimally invasive manner such as by injection. In addition, hydrogels, three-dimensional networks of hydrophilic polymers that are able to swell large amounts of water, can be made to resemble the physical characteristics of soft tissues. Hydrogel materials also generally exhibit high permeability and good biocompatibility making, these materials attractive for use in cell encapsulation and tissue engineering applications. A number of hydrogel materials can be formed via photopolymerization processes mild enough to be carried out in the presence of living cells. This allows one to homogeneously seed cells throughout the scaffold material and to form hydrogels in situ. This review presents advantages of photopolymerization of hydrogels and describes the photoinitiators and materials in current use. Applications of photopolymerized hydrogels in tissue engineering that have been investigated are summarized. © 2002 Elsevier Science Ltd. All rights reserved.

Authors
Nguyen, KT; West, JL
MLA Citation
Nguyen, KT, and West, JL. "Photopolymerizable hydrogels for tissue engineering applications." Biomaterials 23.22 (2002): 4307-4314.
PMID
12219820
Source
scival
Published In
Biomaterials
Volume
23
Issue
22
Publish Date
2002
Start Page
4307
End Page
4314
DOI
10.1016/S0142-9612(02)00175-8

Heparanase and platelet factor-4 induce smooth muscle cell proliferation and migration via bFGF release from the ECM

Basic fibroblast growth factor (bFGF) has been shown to play an instrumental role in the cascade of events leading to restenosis; however, the mechanisms of bFGF activation following vascular injury have remained elusive. We have demonstrated that heparanase and platelet factor-4 (PF4), released from activated platelets at the site of injury, liberate bFGF from the extracellular matrix (ECM) of vascular smooth muscle cells (SMC), resulting in the induction of SMC proliferation and migration. Increases in proliferation and migration were inhibited by treatment with a bFGF-neutralizing antibody, suggesting that proliferation and migration in response to heparanase or PF4 are mediated by bFGF activation. When platelets were seeded on top of SMCs, degranulation products were found to release bFGF from the ECM, increasing cell proliferation and cell migration. Again, these increases in SMC proliferation and migration were inhibited by treatment with an anti-bFGF antibody. Furthermore, these increases in proliferation were completely inhibited by treatment with an anti-heparanase antibody. Platelet degranulation products, such as heparanase and PF4, may liberate bFGF from extracellular sequestration, activating the growth factor and inducing the SMC proliferation and migration that contribute to the wound healing response following vascular injury.

Authors
Myler, HA; West, JL
MLA Citation
Myler, HA, and West, JL. "Heparanase and platelet factor-4 induce smooth muscle cell proliferation and migration via bFGF release from the ECM." Journal of Biochemistry 131.6 (2002): 913-922.
PMID
12038989
Source
scival
Published In
The Journal of Biochemistry
Volume
131
Issue
6
Publish Date
2002
Start Page
913
End Page
922

Implantable, polymeric systems for modulated drug delivery

The ability to deliver therapeutic agents to a patient in a pulsatile or staggered release profile has been a major goal in drug delivery research over the last two decades. This review will cover methods that have been developed to control drug delivery profiles with implantable polymeric systems. Externally and internally controlled systems will be discussed, spanning a range of technologies that include pre-programmed systems, as well as systems that are sensitive to modulated enzymatic or hydrolytic degradation, pH, magnetic fields, ultrasound, electric fields, temperature, light and mechanical stimulation. Implantable systems have the potential to improve the quality of life for patients undergoing therapy with a variable dosing regime by eliminating the need for multiple intravenous injections. Ideally, these systems would also result in increased patient compliance with a given therapy due to the relative ease of self-dosing. © 2002 Elsevier Science B.V. All rights reserved.

Authors
Sershen, S; West, J
MLA Citation
Sershen, S, and West, J. "Implantable, polymeric systems for modulated drug delivery." Advanced Drug Delivery Reviews 54.9 (2002): 1225-1235.
PMID
12393303
Source
scival
Published In
Advanced Drug Delivery Reviews
Volume
54
Issue
9
Publish Date
2002
Start Page
1225
End Page
1235
DOI
10.1016/S0169-409X(02)00090-X

Cell migration through defined, synthetic ECM analogs.

We have developed synthetic hydrogel extracellular matrix (ECM) analogues that can be used to study mechanisms involved in cell migration, such as receptor-ligand interactions and proteolysis. The biomimetic hydrogels consist of bioinert polyethylene glycol diacrylate derivatives with proteolytically degradable peptide sequences included in the backbone of the polymer and adhesive peptide sequences grafted to the network. Hydrogels have been developed that degrade as cells secrete proteolytic enzymes. Adhesive peptide sequences grafted to the hydrogel provide ligands that can interact with receptors on the cell surface to mediate adhesion and spreading. In this study, we have characterized the effects of adhesive ligand density on fibroblast migration through collagenase-degradable and plasmin-degradable hydrogels and on smooth muscle cell migration through elastase-degradable hydrogels. In all three cases, we found that cell migration has a biphasic dependence on adhesion ligand concentration, with optimal migration at intermediate ligand levels. Furthermore, both adhesive and proteolytically degradable sequences were required for cell migration to occur. These synthetic ECM analogues may be useful for 3-D mechanistic studies of many aspects of cell migration

Authors
Gobin, AS; West, JL
MLA Citation
Gobin, AS, and West, JL. "Cell migration through defined, synthetic ECM analogs." The FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16.7 (2002): 751-753.
PMID
11923220
Source
scival
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
16
Issue
7
Publish Date
2002
Start Page
751
End Page
753

Pulsatile release of insulin via photothermally modulated drug delivery

Composites of thermally-sensitive hydrogels and optically-active nanoparticles have been developed for transdermal photothermally modulated drug delivery. Copolymers of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm) exhibit a lower critical solution temperature (LCST) that is slightly above body temperature. Gold-gold sulfide nanoshells have been incorporated into poly(NIPAAm-co-AAm) hydrogels to initiate a temperature change with light. The nanoshells heat upon irradiation at their peak absorption wavelength, causing the collapse of the polymer and the subsequent release of any drug contained within the polymer matrix. For this to occur, the light must pass through the skin and retain enough power to cause significant heating in the nanoshells. Light between 800 and 1200 nm has been shown to have relatively low levels of attenuation in tissue. Composite polymers of the nanoshells and NIPAAm-co-AAm can deliver controlled pulsatile doses of insulin in response to near-IR irradiation. The activity of the released insulin was determined by measuring glucose uptake by adipocytes that had been exposed to photothermally released insulin. The released insulin did not show a loss in activity as compared to the positive control (insulin in saline), thus demonstrating transdermal photothermally modulated drug deliver in vitro.

Authors
Sershen, SR; Halas, NJ; West, JL
MLA Citation
Sershen, SR, Halas, NJ, and West, JL. "Pulsatile release of insulin via photothermally modulated drug delivery." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 1 (2002): 490-491.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
1
Publish Date
2002
Start Page
490
End Page
491

Targeted photothermal tumor therapy using metal nanoshells

Complications associated with invasive malignant tumor excision have led to alternative treatment methods including chemotherapy, photodynamic therapy, and thermal coagulation. Metal nanoshells, which are a new class of optically active nanoparticles, may provide a novel means of targeted photothermal therapy in tumor tissue, minimizing damage to surrounding healthy tissue. Metal nanoshells possess a strong tunable absorption, which can be placed in the near IR where maximal penetration of light through tissue is achieved. When conjugated with a tumor-specific protein, these nanoshells could be systematically injected, but preferentially bound to the tumor site. Near IR light administered at the site would heat the localized nanoshells, killing the tumor. We have successfully conjugated antibodies against oncoproteins to nanoshells and demonstrated specific binding to tumor cells. Furthermore, we have demonstrated photothermally-induced death of nanoshell-bound carcinoma cells in vitro, as well as in vivo. These studies utilized an 821 nm diode laser, and nanoshells fabricated with their plasmon resonance at 821 nm. Cell death was limited to the laser spot, and under control conditions (no nanoshells or no light), no cell death or tissue damage was observed.

Authors
Hirsch, LR; Stafford, RJ; Bankson, JA; Sershen, SR; Price, RE; Hazle, JD; Halas, NJ; West, JL
MLA Citation
Hirsch, LR, Stafford, RJ, Bankson, JA, Sershen, SR, Price, RE, Hazle, JD, Halas, NJ, and West, JL. "Targeted photothermal tumor therapy using metal nanoshells." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 1 (2002): 530-531.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
1
Publish Date
2002
Start Page
530
End Page
531

The effects of adhesivity on cell migration through biomimetic matrices

We have developed synthetic hydrogel extracellular matrix (ECM) analogs that can be used to study mechanisms involved in cell migration, such as receptor-ligand interactions and proteolysis. The biomimetic hydrogels consist of bioinert polyethylene glycol diacrylate derivatives with proteolytically degradable peptide sequences included in the backbone of the polymer and adhesive peptide sequences grafted to the network. Hydrogels have been developed that degrade as cells secrete proteolytic enzymes. Adhesive peptide sequences grafted to the hydrogel provide ligands that can interact with receptors on the cell surface to mediate adhesion and spreading. In this study, we have characterized the effects of adhesive ligand density on fibroblast migration through collagenase-degradable plasmin-degradable hydrogels and on smooth muscle cell migration through elastase-degradable hydrogels. In all three cases, we found that cell migration has a biphasic-dependence on adhesion ligand concentration, with optimal migration at intermediate ligand levels. Furthermore, both adhesive and proteolytically degradable sequences were required for cell migration to occur. These synthetic ECM analogs may be useful for three-dimensional mechanistic studies of many aspects of cell migration.

Authors
Gobin, A; West, J
MLA Citation
Gobin, A, and West, J. "The effects of adhesivity on cell migration through biomimetic matrices." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 1 (2002): 578-579.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
1
Publish Date
2002
Start Page
578
End Page
579

Val-Ala-Pro-Gly, an elastin derived non-integrin ligand: Cell adhesion and specificity

The non-integrin derived peptide VAPG maybe useful as a biospecific cell adhesion ligand for smooth muscle cells. By grafting the peptide sequence into a hydrogel material, we were able to assess its effects on cell adhesion and spreading. These materials are photopolymerizable hydrogels based on acrylate-terminated derivatives of polyethylene glycol (PEG). PEG diacrylate derivatives can be mixed with adhesive peptide-modified PEG monoacrylate derivatives. Following photopolymerization, the PEG monoacrylate derivatives are grafted into the hydrogel network formed by the PEG diacrylate. This results in covalent immobilization of the adhesive peptides to the hydrogel via a flexible linker chain. The resistance of PEG to protein adsorption makes it an ideal material for this model system, since cell-material interactions are essentially limited to the biomolecules that are covalently incorporated into the material. In this case we were able to demonstrate that VAPG is specific for adhesion of smooth muscle cells, and this can aid in the design of tissue engineered vascular grafts.

Authors
Gobin, A; West, J
MLA Citation
Gobin, A, and West, J. "Val-Ala-Pro-Gly, an elastin derived non-integrin ligand: Cell adhesion and specificity." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 1 (2002): 866-867.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
1
Publish Date
2002
Start Page
866
End Page
867

Development of a YIGSR peptide-modified polyurethaneurea to enhance endothelialization

We have developed a peptide-modified bioactive polyurethaneurea to enhance vascular graft endothelialization. YIGSR peptides were incorporated into the polymer backbone, and successful incorporation of the peptides was confirmed by NMR, contact angle measurement, and ESCA. Uniform distribution of peptides on the surface was observed using a fluorescent probe capable of reacting with tyrosine residues on the peptides. Hard segment domains were observed to be arranged parallel to the plane of the surface using AFM. Endothelial cell adhesion, spreading, proliferation, migration, and extracellular matrix production were improved on bioactive polyurethaneurea (PUUYIGSR) compared to control (PUUPPD). Additionally, competitive inhibition of endothelial cell attachment and spreading was found when cells were incubated in the presence of soluble YIGSR peptides.

Authors
Jun, H-W; West, J
MLA Citation
Jun, H-W, and West, J. "Development of a YIGSR peptide-modified polyurethaneurea to enhance endothelialization." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 1 (2002): 821-822.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
1
Publish Date
2002
Start Page
821
End Page
822

Genetic modification of smooth muscle cells to enhance mechanical properties of tissue engineered constructs

A number of strategies have been investigated to enhance the mechanical stability of engineered tissues. In this report, we utilized lysyl oxidase (LO) to enzymatically crosslink extracellular matrix (ECM) proteins, particularly collagen and elastin, to enhance the mechanical integrity of the ECM and thereby impart mechanical strength to the engineered tissue. Vascular smooth muscle cells (VSMCs) were liposomally transfected with the LO gene. Western analysis confirmed increased LO expression. Increased LO activity was demonstrated as increased levels of desmosine, a product of LO crosslinking, in the ECM. The mechanical effects of altered crosslink densities within tissue engineered constructs were demonstrated in a VSMC-populated collagen gel model. Smooth muscle cells transfected with lysyl oxidase were seeded in collagen gels; the tensile strength and elastic modulus in these constructs increased by approximately two-fold compared to constructs seeded with mock transfected VSMCs. Compositional analysis of the ECM deposited by the transformed cells showed similar collagen and elastin levels, and cell proliferation was similar as well. Thus, increased mechanical properties were attributed to ECM crosslinking.

Authors
Elbjeirami, W; Yonter, E; West, J
MLA Citation
Elbjeirami, W, Yonter, E, and West, J. "Genetic modification of smooth muscle cells to enhance mechanical properties of tissue engineered constructs." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 1 (2002): 773-774.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
1
Publish Date
2002
Start Page
773
End Page
774

Localized delivery of anti-heparanase for inhibition of restenosis

We have used hydrogel systems to locally deliver a possible inhibitor of restenosis. This inhibitor is an antibody against the active site of platelet-derived heparanase. This enzyme is involved in the activation of basic fibroplast growth factor stored in the extracellular matrix following vascular injury. The antibody was found to inhibit bFGF release from the arterial wall and to decrease intimal thickening by 60% (n=7; p<0.00003).

Authors
Myler, HA; Rice, E; West, JL
MLA Citation
Myler, HA, Rice, E, and West, JL. "Localized delivery of anti-heparanase for inhibition of restenosis." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 1 (2002): 528-529.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
1
Publish Date
2002
Start Page
528
End Page
529

Optically controllable materials: Potential valves and actuators in microfluidics and MEMS

Composite materials consisting of optically active nanoparticles embedded within a thermally sensitive polymer selectively collapse when irradiated by light that matches the peak absorption wavelength of the nanoparticles. A copolymer of N-isopropylacrylamide and acrylamide exhibits a lower critical solution temperature (LCST) that is dependent on the relative amounts of each monomer in the polymer. Raising the temperature of the copolymer above the LCST initiates a rapid, reversible collapse. Optically active nanoparticles have been incorporated into NIPAAm/AAm hydrogels for the purpose of initiating a temperature increase via targeted absorption of near IR and green light. Gold nanoshells consist of a thin layer of gold surrounding a silica core, and altering the core/shell ratio allows the absorption of the nanoshells to be tuned over the visible and near IR spectrum. Gold colloid absorbs green light strongly at 532 nm. Two sets of composite hydrogels were fabricated, each containing one of the two nanoparticles. The nanoshell-composite hydrogels collapse in response to near-infrared irradiation but do not react to green light. The opposite behavior occurs for the colloid-composite hydrogels. This independent optical addressability should prove useful in a wide range of applications such as microfluidics and MEMS.

Authors
Sershen, SR; Ng, M; Halas, NJ; West, JL
MLA Citation
Sershen, SR, Ng, M, Halas, NJ, and West, JL. "Optically controllable materials: Potential valves and actuators in microfluidics and MEMS." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 3 (2002): 1822-1823.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
3
Publish Date
2002
Start Page
1822
End Page
1823

Tethered basic fibroblast growth factor increases vascular cell proliferation

Scaffolds should direct and promote tissue formation of tissue-engineered constructs. To optimize tissue formation, we propose the use of polyethylene glycol (PEG) conjugated bioactive factors that can be covalently immobilized to PEG diacrylate hydrogel scaffolds. We have demonstrated that the growth factor, basic fibroblast growth factor (bFGF), retains its activity following attachment to PEG and incorporation into photopolymerized hydrogel scaffolds. Tethered bFGF significantly increased SMC proliferation on RGDS-modified PEG diacrylate hydrogels. Covalently grafting bFGF to the hydrogel stimulated increased cell number exceeding that seen when the unmodified, soluble form of bFGF was used. Thus, incorporating tethered bFGF within scaffolds is a promising method for optimizing cell proliferation, an important aspect of tissue formation.

Authors
DeLong, SA; West, JL
MLA Citation
DeLong, SA, and West, JL. "Tethered basic fibroblast growth factor increases vascular cell proliferation." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 1 (2002): 815-816.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
1
Publish Date
2002
Start Page
815
End Page
816

Tissue engineered vascular grafts: Elastic polyethylene glycol hydrogel scaffolds for culture under pulsatile flow conditions

Increased demand for small diameter vascular grafts has spurred the development of scaffold materials for tissue engineered vascular grafts. We have investigated one such material, photopolymerizable polyethylene glycol (PEG) hydrogels. The mechanical properties of these PEG hydrogels may be tailored for a given application to provide desired elasticity and tensile strength. The Young's modulus and ultimate tensile strength may be increased by increasing the polymer concentration, lowering the polymer molecular weight, or by combining a small fraction of low molecular weight polymer with a higher molecular weight polymer. Cells seeded within these PEG hydrogels retain viability throughout 4 weeks in culture, with no differences in viability across the thickness of the hydrogel. Tubular PEG hydrogel constructs were seeded with vascular smooth muscle cells and cultured under pulsatile flow conditions. After 4 days, the Young's modulus and ultimate tensile strength of the constructs were significantly higher compared to static controls. Cells in the hydrogels also produced more extracellular matrix in pulsatile culture, as evidenced by hydroxyproline content, compared to static controls. These results suggest that PEG hydrogels may be suitable materials for vascular tissue engineering.

Authors
Schmedlen, RH; Nyugen, KT; West, JL
MLA Citation
Schmedlen, RH, Nyugen, KT, and West, JL. "Tissue engineered vascular grafts: Elastic polyethylene glycol hydrogel scaffolds for culture under pulsatile flow conditions." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 1 (2002): 813-814.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
1
Publish Date
2002
Start Page
813
End Page
814

Nitric-oxide generating hydrogels inhibit intimal thickening and promote endothelial cell proliferation

Nitric oxide-generating hydrogels have been shown to inhibit smooth muscle cell proliferation and platelet adhesion, as well as promote endothelial cell proliferation; for this reason these hydrogels should be useful in preventing restenosis, or vessel re-occlusion, following balloon angioplasty. Over 600,000 percutaneous transluminal coronary angioplasty (PTCA) procedures are performed annually in the U.S. [1]; unfortunately, 30-40% of patients treated with PTCA experience failure due to restenosis [2]. We have developed nitric oxide (NO)- generating hydrogels that release NO over a period of days to weeks, depending on material design. They are able to significantly reduce platelet adhesion to collagen and inhibit smooth muscle cell proliferation in vitro. In addition, we have covalently grafted a cell adhesion peptide into the NO-generating hydrogels and assessed the ability of endothelial cells (EC) to proliferate on the surface. ECs showed significantly higher rates of proliferation on the NO-generating hydrogels as compared to controls. The perivascular application of NO-generating hydrogels significantly reduced neointimal formation in an experimental balloon angioplasty model as compared to controls. The combined effects of these NO-generating hydrogels make them well suited for incorporation into blooding-contacting devices and for use as a stent coating or stent replacement to prevent restenosis following balloon angioplasty.

Authors
Lipke, E; Masters, K; Myler, H; Shen, C; West, J
MLA Citation
Lipke, E, Masters, K, Myler, H, Shen, C, and West, J. "Nitric-oxide generating hydrogels inhibit intimal thickening and promote endothelial cell proliferation." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 1 (2002): 475-476.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
1
Publish Date
2002
Start Page
475
End Page
476

A rapid, near infrared, whole blood immunoassay using metal nanoshells

The development of a rapid, whole blood immunoassay with the capacity to detect various analytes would greatly benefit point-of-care or public health applications, where there is a strong demand for the rapid, high throughput screening of blood-born species. Immunoassays, with their high affinity/specificity, show the most promise for implementing such a system. Nevertheless, conventional methods, such as the Enzyme Linked Immunosorbent Assays (ELISAs), have failed to develop a robust, rapid, whole blood assay, as they require time-consuming sample purification, incubation, and rinsing steps prior to analysis. We have used a new class of optically-active nanoparticles called metal nanoshells to develop a new rapid, near-infrared (NIR) immunoassay capable of detecting very low concentration of analytes in whole blood within minutes without any sample preparation.

Authors
Hirsch, LR; Halas, NJ; West, JL
MLA Citation
Hirsch, LR, Halas, NJ, and West, JL. "A rapid, near infrared, whole blood immunoassay using metal nanoshells." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 2 (2002): 1646-1647.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
2
Publish Date
2002
Start Page
1646
End Page
1647

Probing the optical near field of a nanolens

Dielectric core-metal shell nanoparticles, known as metal nanoshells, were shown to possess broadly tunable plasmon resonances whose frequency can be controlled by the relative thickness of the nanoparticle layers. As such, the "nanolens" was characterized by measuring the local electromagnetic field at the nanoshell surface as a function of the nanoparticle's core and shell dimensions via the Surface Enhanced Raman Scattering (SERS) response from a monolayer of nonresonant adsorbate molecules bound to the nanoparticle surface.

Authors
Jackson, JB; Westcott, SL; Hirsch, LR; West, JL; Halas, NJ
MLA Citation
Jackson, JB, Westcott, SL, Hirsch, LR, West, JL, and Halas, NJ. "Probing the optical near field of a nanolens." Conference on Quantum Electronics and Laser Science (QELS) - Technical Digest Series 74 (2002): 40-41.
Source
scival
Published In
Conference on Quantum Electronics and Laser Science (QELS) - Technical Digest Series
Volume
74
Publish Date
2002
Start Page
40
End Page
41

Synthetic ECM analogs: Biofunctional polymers for tissue engineering.

Authors
West, JL
MLA Citation
West, JL. "Synthetic ECM analogs: Biofunctional polymers for tissue engineering." ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 222 (August 2001): U419-U419. (Academic Article)
Source
manual
Published In
ACS National Meeting Book of Abstracts
Volume
222
Publish Date
2001
Start Page
U419
End Page
U419

Heparinase and platelet factor-4 release active basic fibroblast growth factor from the extracellular matrix

Authors
Myler, HA; West, JL
MLA Citation
Myler, HA, and West, JL. "Heparinase and platelet factor-4 release active basic fibroblast growth factor from the extracellular matrix." FASEB JOURNAL 15.4 (March 2001): A246-A246. (Academic Article)
Source
manual
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
15
Issue
4
Publish Date
2001
Start Page
A246
End Page
A246

Tissue engineering in the cardiovascular system: Progress toward a tissue engineered heart

Achieving the lofty goal of developing a tissue engineered heart will likely rely on progress in engineering the various components: blood vessels, heart valves, and cardiac muscle. Advances in tissue engineered vascular grafts have shown the most progress to date. Research in tissue-engineered vascular grafts has focused on improving scaffold design, including mechanical properties and bioactivity; genetically engineering cells to improve graft performance; and optimizing tissue formation through in vitro mechanical conditioning. Some of these same approaches have been used in developing tissue engineering heart valves and cardiac muscle as well. Continued advances in scaffold technology and a greater understanding of vascular cell biology along with collaboration among engineers, scientists, and physicians will lead to further progress in the field of cardiovascular tissue engineering and ultimately the development of a tissue-engineered heart. © 2001 Wiley-Liss, Inc.

Authors
Mann, BK; West, JL
MLA Citation
Mann, BK, and West, JL. "Tissue engineering in the cardiovascular system: Progress toward a tissue engineered heart." Anatomical Record 263.4 (2001): 367-371.
PMID
11500813
Source
scival
Published In
Anatomical Record
Volume
263
Issue
4
Publish Date
2001
Start Page
367
End Page
371
DOI
10.1002/ar.1116

Tethered-TGF-β increases extracellular matrix production of vascular smooth muscle cells

Biomaterials developed for tissue engineering and wound healing applications need to support robust cell adhesion, yet also need to be replaced by new tissue synthesized by those cells. In order to maintain mechanical integrity of the tissue, the cells must generate sufficient extracellular matrix before the scaffold is degraded. We have previously shown that materials containing cell adhesive ligands to promote or improve cell adhesion can decrease extracellular matrix production (Mann et al., Modification of surfaces with cell adhesion peptides alters extracellular matrix deposition. Biomaterials 1999;20:2281-6). Such decreased matrix production by cells in tissue engineering scaffolds may result in tissue failure. However, we have found that TGF-β1 can be used in scaffolds to dramatically increase matrix production. Matrix production by vascular smooth muscle cells grown on adhesive ligand-modified glass surfaces and in PEG hydrogels containing covalently bound adhesive ligands was increased in the presence of 0.04pmol/ml (1ng/ml) TGF-β1. TGF-β1 can counteract the effect of these adhesive ligands on matrix production; matrix production could be increased even above that observed in the absence of adhesive peptides. Further, TGF-β1 covalently immobilized to PEG retained its ability to increase matrix production. Tethering TGF-β1 to the polymer scaffold resulted in a significant increase in matrix production over the same amount of soluble TGF-β1. Copyright © 2001 Elsevier Science Ltd.

Authors
Mann, BK; Schmedlen, RH; West, JL
MLA Citation
Mann, BK, Schmedlen, RH, and West, JL. "Tethered-TGF-β increases extracellular matrix production of vascular smooth muscle cells." Biomaterials 22.5 (2001): 439-444.
PMID
11214754
Source
scival
Published In
Biomaterials
Volume
22
Issue
5
Publish Date
2001
Start Page
439
End Page
444
DOI
10.1016/S0142-9612(00)00196-4

Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: Synthetic ECM analogs for tissue engineering

Photopolymerizable polyethylene glycol (PEG) derivatives have been investigated as hydrogel tissue engineering scaffolds. These materials have been modified with bioactive peptides in order to create materials that mimic some of the properties of the natural extracellular matrix (ECM). The PEG derivatives with proteolytically degradable peptides in their backbone have been used to form hydrogels that are degraded by enzymes involved in cell migration, such as collagenase and elastase. Cell adhesive peptides, such as the peptide RGD, have been grafted into photopolymerized hydrogels to achieve biospecific cell adhesion. Cells seeded homogeneously in the hydrogels during photopolymerization remain viable, proliferate, and produce ECM proteins. Cells can also migrate through hydrogels that contain both proteolytically degradable and cell adhesive peptides. The biological activities of these materials can be tailored to meet the requirements of a given tissue engineering application by creating a mixture of various bioactive PEG derivatives prior to photopolymerization. Copyright © 2001 Elsevier Science Ltd.

Authors
Mann, BK; Gobin, AS; Tsai, AT; Schmedlen, RH; West, JL
MLA Citation
Mann, BK, Gobin, AS, Tsai, AT, Schmedlen, RH, and West, JL. "Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: Synthetic ECM analogs for tissue engineering." Biomaterials 22.22 (2001): 3045-3051.
PMID
11575479
Source
scival
Published In
Biomaterials
Volume
22
Issue
22
Publish Date
2001
Start Page
3045
End Page
3051
DOI
10.1016/S0142-9612(01)00051-5

An opto-mechanical nanoshell-polymer composite

Metal nanoshells, which are nanoparticles consisting of a dielectric core surrounded by a metal shell, have an optical response dictated by the plasmon resonance. This optical resonance leads to large extinction cross-sections, which are typically several times the physical cross-section of the particles. The wavelength at which the resonance occurs depends on the core and shell sizes, allowing nanoshells to be tailored for applications. In this paper, we demonstrate how incorporating nanoshells transforms a thermoresponsive polymer into a photothermally responsive nanoshell-polymer composite. When the thermoresponsive polymer, co-N-isopropylacrylamide-acrylamide (NIPAAm-co-AAm), is heated, the polymer undergoes a reversible decrease in volume. Pristine NIPAAm-co-AAm does not inherently absorb visible or near infrared light. However, by incorporating metal nanoshell particles with a resonance that has been placed at 832 nm into the NIPAAm-co-Aam, nanoshell-polymer composite hydrogels are fabricated. When the composite is illuminated with a diode laser at 832 nm, the nanoshells absorb light and convert it to heat. This induces a reversible and repeatable light-driven collapse of the composite with a weight change of 90% after illumination at 1.8 Wcm-2.

Authors
Sershen, SR; Westcott, SL; West, JL; Halas, NJ
MLA Citation
Sershen, SR, Westcott, SL, West, JL, and Halas, NJ. "An opto-mechanical nanoshell-polymer composite." Applied Physics B: Lasers and Optics 73.4 (2001): 379-381.
Source
scival
Published In
Applied Physics B
Volume
73
Issue
4
Publish Date
2001
Start Page
379
End Page
381
DOI
10.1007/s003400100689

Nanoshell-polymer composites for photothermally modulated drug delivery

A study of nanoshell-polymer composites for photothermally modulated drug delivery was performed. It was observed that nanoshell-composite hydrogels released more BSA than non-irradiated hydrogels in response to near-infrared irradiation. The copolymer was heated by the interaction between incident near infrared light and nanoshells and forced the hydrogel to collapse. The collapse initiated faster release rate of the drugs.

Authors
Sershen, SR; West, JL; Westcott, SL; Halas, NJ
MLA Citation
Sershen, SR, West, JL, Westcott, SL, and Halas, NJ. "Nanoshell-polymer composites for photothermally modulated drug delivery." Conference on Lasers and Electro-Optics Europe - Technical Digest (2001): 404-405.
Source
scival
Published In
Conference on Lasers and Electro-Optics Europe - Technical Digest
Publish Date
2001
Start Page
404
End Page
405

Metal nanoshells: A novel substrate for immunoassays

The use of metal nanoshells as a substrate for optical detection of analytes in complex biological solutions was examined. The near-infrared surface-enhanced Raman scattering and gold silica nanoshells were used to perform the analysis. Atomic force microscopic (AFM) analysis of antibody-labeled nanoshell binding was also performed to assess nanoshell-antibody activity. The study results confirmed the synthesis of near-IR resonant nanoshells with 198 nm diameter core. The presence of active antibody on nanoshell surface was confirmed by AFM analysis.

Authors
Hirsch, LR; West, JL; Jackson, JB; Moran, CE; Halas, NJ
MLA Citation
Hirsch, LR, West, JL, Jackson, JB, Moran, CE, and Halas, NJ. "Metal nanoshells: A novel substrate for immunoassays." Conference on Lasers and Electro-Optics Europe - Technical Digest (2001): 405--.
Source
scival
Published In
Conference on Lasers and Electro-Optics Europe - Technical Digest
Publish Date
2001
Start Page
405-

Nitric oxide-releasing hydrogels for the prevention of thrombosis and restenosis

Authors
Bohl, KS; West, JL
MLA Citation
Bohl, KS, and West, JL. "Nitric oxide-releasing hydrogels for the prevention of thrombosis and restenosis." CIRCULATION 102.18 (October 2000): 734-734. (Academic Article)
Source
manual
Published In
Circulation
Volume
102
Issue
18
Publish Date
2000
Start Page
734
End Page
734

Temperature-sensitive polymer-nanoshell composites for photothermally modulated drug delivery.

Composites of thermally sensitive hydrogels and optically active nanoparticles have been developed for the purpose of photothermally modulated drug delivery. Copolymers of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm) exhibit a lower critical solution temperature (LCST) that is slightly above body temperature. When the temperature of the copolymer exceeds the LCST, the hydrogel collapses, causing a burst release of any soluble material held within the hydrogel matrix. Gold-gold sulfide nanoshells, a new class of nanoparticles designed to strongly absorb near-infrared light, have been incorporated into poly(NIPAAm-co-AAm) hydrogels for the purpose of initiating a temperature change with light; light at wavelengths between 800 and 1200 nm is transmitted through tissue with relatively little attenuation, absorbed by the nanoparticles, and converted to heat. Significantly enhanced drug release from composite hydrogels has been achieved in response to irradiation by light at 1064 nm. We have investigated the release of methylene blue and proteins of varying molecular weight. Additionally, the nanoshell-composite hydrogels can release multiple bursts of protein in response to repeated near-IR irradiation.

Authors
Sershen, SR; Westcott, SL; Halas, NJ; West, JL
MLA Citation
Sershen, SR, Westcott, SL, Halas, NJ, and West, JL. "Temperature-sensitive polymer-nanoshell composites for photothermally modulated drug delivery." Journal of biomedical materials research 51.3 (September 2000): 293-298.
PMID
10880069
Source
epmc
Published In
Journal of Biomedical Materials Research
Volume
51
Issue
3
Publish Date
2000
Start Page
293
End Page
298
DOI
10.1002/1097-4636(20000905)51:3<293::aid-jbm1>3.0.co;2-t

Temperature-sensitive polymer-nanoshell composites for photothermally modulated drug delivery

Composites of thermally sensitive hydrogels and optically active nanoparticles have been developed for the purpose of photothermally modulated drug delivery. Copolymers of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm) exhibit a lower critical solution temperature (LCST) that is slightly above body temperature. When the temperature of the copolymer exceeds the LCST, the hydrogel collapses, causing a burst release of any soluble material held within the hydrogel matrix. Gold-gold sulfide nanoshells, a new class of nanoparticles designed to strongly absorb near-infrared light, have been incorporated into poly(NIPAAm-co-AAm) hydrogels for the purpose of initiating a temperature change with light; light at wavelengths be-tween 800 and 1200 nm is transmitted through tissue with relatively little attenuation, absorbed by the nanoparticles, and converted to heat. Significantly enhanced drug release from composite hydrogels has been achieved in response to irradiation by light at 1064 nm. We have investigated the release of methylene blue and proteins of varying molecular weight. Additionally, the nanoshell-composite hydrogels can release multiple bursts of protein in response to repeated near-IR irradiation. (C) 2000 John Wiley \& Sons, Inc.

Authors
Sershen, SR; Westcott, SL; Halas, NJ; West, JL
MLA Citation
Sershen, SR, Westcott, SL, Halas, NJ, and West, JL. "Temperature-sensitive polymer-nanoshell composites for photothermally modulated drug delivery." JOURNAL OF BIOMEDICAL MATERIALS RESEARCH 51.3 (September 2000): 293-298. (Academic Article)
Source
manual
Published In
Journal of Biomedical Materials Research
Volume
51
Issue
3
Publish Date
2000
Start Page
293
End Page
298
DOI
10.1002/1097-4636(20000905)51:33.0.CO;2-T

Nitric oxide-generating polymers reduce platelet adhesion and smooth muscle cell proliferation

We have developed polymeric biomaterials capable of providing localized and sustained production of nitric oxide (NO) for the prevention of thrombosis and restenosis. In the current study, we have characterized the kinetics of NO production by these materials and investigated their efficacy in reducing platelet adhesion and smooth muscle cell proliferation in vitro. Three nitric oxide donors with different half-lives were covalently incorporated into photopolymerized polyethylene glycol hydrogels. Under physiological conditions, NO was produced by these hydrogels over periods ranging from hours to months, depending upon the polymer formulation. NO production was inhibited at acidic pH, which may be useful for storage of the materials. The NO-releasing materials successfully inhibited smooth muscle cell growth in culture. Platelet adhesion to collagen-coated surfaces was also inhibited following exposure of whole blood to NO-producing hydrogels. The effects of NO production by these hydrogels on platelet adhesion and the proliferation of smooth muscle cells suggest that these materials could reduce thrombosis and restenosis following procedures such as balloon angioplasty. (C) 2000 Elsevier Science Ltd.

Authors
Bohl, KS; West, JL
MLA Citation
Bohl, KS, and West, JL. "Nitric oxide-generating polymers reduce platelet adhesion and smooth muscle cell proliferation." Biomaterials 21.22 (2000): 2273-2278.
PMID
11026633
Source
scival
Published In
Biomaterials
Volume
21
Issue
22
Publish Date
2000
Start Page
2273
End Page
2278
DOI
10.1016/S0142-9612(00)00153-8

Biomaterials: Preface

Authors
West, JL; Hubbell, JA
MLA Citation
West, JL, and Hubbell, JA. "Biomaterials: Preface." Biomaterials 21.22 (2000): 2213--.
Source
scival
Published In
Biomaterials
Volume
21
Issue
22
Publish Date
2000
Start Page
2213-
DOI
10.1016/S0142-9612(00)00223-4

Applications of nanotechnology to biotechnology

The ability to systematically modify the properties of nanostructures by controlling their structure and their surface properties at a nanoscale level makes them extremely attractive candidates for use in biological contexts, from fundamental scientific studies to commercially viable technologies.

Authors
West, JL; Halas, NJ
MLA Citation
West, JL, and Halas, NJ. "Applications of nanotechnology to biotechnology." Current Opinion in Biotechnology 11.2 (2000): 215-217.
PMID
10753774
Source
scival
Published In
Current Opinion in Biotechnology
Volume
11
Issue
2
Publish Date
2000
Start Page
215
End Page
217
DOI
10.1016/S0958-1669(00)00082-3

Temperature-sensitive polymer-nanoshell composites for photothermally modulated drug delivery

Composites of thermally sensitive hydrogels and optically active nanoparticles have been developed for the purpose of photothermally modulated drug delivery. Copolymers of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm) exhibit a lower critical solution temperature (LCST) that is slightly above body temperature. When the temperature of the copolymer exceeds the LCST, the hydrogel collapses, causing a burst release of any soluble material held within the hydrogel matrix. Gold-gold sulfide nanoshells, a new class of nanoparticles designed to strongly absorb near-infrared light, have been incorporated into poly(NIPAAm-co-AAm) hydrogels for the purpose of initiating a temperature change with light; light at wavelengths between 800 and 1200 nm is transmitted through tissue with relatively little attenuations absorbed by the nanoparticles, and converted to heat. Significantly enhanced drug-release from composite hydrogels has been achieved in response to irradiation by light 1064 nm. We have investigated the release of methylene blue and proteins of varying molecular weight. Additionally, the nanoshell-composite hydrogels can release multiple bursts of protein in response to repeated near-IR irradiation. (C) 2000 John Wiley and Sons, Inc.

Authors
Sershen, SR; Westcott, SL; Halas, NJ; West, JL
MLA Citation
Sershen, SR, Westcott, SL, Halas, NJ, and West, JL. "Temperature-sensitive polymer-nanoshell composites for photothermally modulated drug delivery." Journal of Biomedical Materials Research 51.3 (2000): 293-298.
Source
scival
Published In
Journal of Biomedical Materials Research
Volume
51
Issue
3
Publish Date
2000
Start Page
293
End Page
298
DOI
10.1002/1097-4636(20000905)51:3<293::AID-JBM1>3.0.CO;2-T

Photopolymerized hydrogels as scaffolds for tissue engineered vascular grafts

A study was conducted to examine viability, DNA content, proliferation, and matrix production of SMCs and ECs in PEGDA hydrogels. Over four weeks, SMCs and ECs remained viable. Through one week, DNA increased significantly, cells stained positive for proliferating cell nuclear antigen, and cells produced collagen, indicating that cells within PEG-based hydrogel scaffolds are involved in forming new tissue. Also, the mechanical properties of PEGDA hydrogels; were examined. Hydrogels of 3400 Da had a Young's modulus of 2.3×105 Pa and an ultimate tensile strength of 3.1× 104 Pa, while the 6000 and 10,000 Da hydrogels had a Young's modulus and ultimate tensile strength an order of magnitude lower. The 20% wt 600/6000 hydrogel blend significantly increased Young's modulus.

Authors
Schmedlen, R; Mann, B; West, J
MLA Citation
Schmedlen, R, Mann, B, and West, J. "Photopolymerized hydrogels as scaffolds for tissue engineered vascular grafts." Annals of Biomedical Engineering 28.SUPPL. 1 (2000): S-118.
Source
scival
Published In
Annals of Biomedical Engineering
Volume
28
Issue
SUPPL. 1
Publish Date
2000
Start Page
S
End Page
118

Metal nanoshells as a novel substrate for biosensing applications

The possibility of functionalizing the nanoshell surface with antibodies to detect biomolecules via surface-enhanced Raman scattering (SERS) was examined. Nanoshells were conjugated with antirabbit IgG. AFM revealed that antibody-conjugated nanoshells successfully bind to antigen-coated surfaces of different concentration, confirming the presence of active antibody on nanoshell surfaces.

Authors
Hirsch, L; Jackson, J; Moran, C; Halas, N; West, J
MLA Citation
Hirsch, L, Jackson, J, Moran, C, Halas, N, and West, J. "Metal nanoshells as a novel substrate for biosensing applications." Annals of Biomedical Engineering 28.SUPPL. 1 (2000): S-97.
Source
scival
Published In
Annals of Biomedical Engineering
Volume
28
Issue
SUPPL. 1
Publish Date
2000
Start Page
S
End Page
97

Synthetic ECM analogs as tissue engineering scaffolds

A study was performed to evaluate three proteolytically degradable PEG hydrogels formed by including a degradable peptide in the polymer backbone: LGPA for a collagenase-sensitive polymer, NRV for a plasmin-sensitive polymer, and a polyalanine for an elastase-sensitive polymer. It was shown that the ligands significantly increase adhesion to smooth muscle cells (SMCs). Also, covalently tethered transforming growth factor-beta to the hydrogel scaffold caused increased ECM protein production by SMC was covalently tethered.

Authors
Mann, B; Goin, A; Tsai, A; West, J
MLA Citation
Mann, B, Goin, A, Tsai, A, and West, J. "Synthetic ECM analogs as tissue engineering scaffolds." Annals of Biomedical Engineering 28.SUPPL. 1 (2000): S-122.
Source
scival
Published In
Annals of Biomedical Engineering
Volume
28
Issue
SUPPL. 1
Publish Date
2000
Start Page
S
End Page
122

Temperature-sensitive polymer-nanoshell composites for photothermally modulated drug delivery

An overview is given on the composites for thermally-sensitive hydrogels and optically active nanoparticles developed for photothermally modulated drug delivery. Focus is on copolymers of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm).

Authors
Sershen, S; Westcott, S; Halas, N; West, J
MLA Citation
Sershen, S, Westcott, S, Halas, N, and West, J. "Temperature-sensitive polymer-nanoshell composites for photothermally modulated drug delivery." Annals of Biomedical Engineering 28.SUPPL. 1 (2000): S-22.
Source
scival
Published In
Annals of Biomedical Engineering
Volume
28
Issue
SUPPL. 1
Publish Date
2000
Start Page
S
End Page
22

Near-infrared thermally-induced cell death using metal nanoshells

Antibodies were conjugated to metal nanoshells with retained activity. Nanoshells demonstrated local photothermally-induced death of human dermal fibroblasts (HDFs) in vitro. Gold-gold sulfide nanoshells with a peak absorbance at 830nm were incubated with HDFs, followed by irradiation for 30 s, 1.5, 10, and 20 min. Control surfaces were treated under identical conditions without the nanoshells. In general, significant results were obtained.

Authors
Hirsch, L; West, J
MLA Citation
Hirsch, L, and West, J. "Near-infrared thermally-induced cell death using metal nanoshells." Annals of Biomedical Engineering 28.SUPPL. 1 (2000): S-96.
Source
scival
Published In
Annals of Biomedical Engineering
Volume
28
Issue
SUPPL. 1
Publish Date
2000
Start Page
S
End Page
96

Design issues for a mission to exploit the gravitational lensing effect at 550 AU

Reported herein are the first results of a NASA-sponsored study at the Jet Propulsion Laboratory (JPL), California Institute of Technology, exploring the scientific promise and technological viability of a mission to exploit the gravitational lensing effect of the Sun to obtain huge antenna gains for electromagnetic waves grazing the Sun's disk. With regard to scientific promise, these results, reported at about the halfway point of the study, substantiate the huge antenna gains offered by, as it will be called here, a Solar Gravitational Telescope (SGT) and point to the instrument's potential promise as a ``discovery machine'' but suggest considerable limitations to the telescope's usefulness as a general purpose astrophysical research tool. These limitations are seen to arise, primarily, from the geometry and scale of the ``virtual'' telescope which must be achieved and maintained to utilize the lensing effect and the turbulence effects of the Sun's plasma on the observed target's signal. With regard to technological viability, the preliminary results suggest a very aggressive use of unproven, as-yet-unflown new technology will be required to enable the desired science observations and mission durations approaching the short (3-10 year) NASA-targeted mission duration goal. Key needed new technologies are advanced propulsion, lightweight telescopes, membrane mirrors, inflatable/rigidizeable structures, and novel coronagraphic techniques. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.

Authors
West, JL
MLA Citation
West, JL. "Design issues for a mission to exploit the gravitational lensing effect at 550 AU." ACTA ASTRONAUTICA 44.2-4 (January 1999): 99-107. (Academic Article)
Source
manual
Published In
Acta Astronautica
Volume
44
Issue
2-4
Publish Date
1999
Start Page
99
End Page
107
DOI
10.1016/S0094-5765(99)00034-X

Modification of surfaces with cell adhesion peptides alters extracellular matrix deposition

The goal of the current study was to evaluate matrix protein synthesis by cells cultured on materials that had been modified with cell adhesion ligands. We examined the effects of surface peptide density and of peptides with different affinities on the extracellular matrix production of smooth muscle cells, endothelial cells and fibroblasts. While initial adhesion was greatest on the higher density peptide surfaces, all cell types exhibited decreased matrix production on the more highly adhesive surfaces. Similarly, when different peptides were evaluated, matrix production was the lowest on the most adhesive surface and highest on the least adhesive surface. These results suggest that extracellular matrix synthesis may be regulated, to some extent, by signal transduction initiated by adhesion events. This may pose limitations for use of bioactive materials as tissue engineering scaffolds, as matrix production is an important aspect of tissue formation. However, it may be possible to increase matrix production on highly adhesive surfaces using exogenous factors. TGF-β was shown to increase matrix production by both smooth muscle cells and endothelial cells. Copyright (C) 1999 Elsevier Science Ltd.

Authors
Mann, BK; Tsai, AT; Scott-Burden, T; West, JL
MLA Citation
Mann, BK, Tsai, AT, Scott-Burden, T, and West, JL. "Modification of surfaces with cell adhesion peptides alters extracellular matrix deposition." Biomaterials 20.23-24 (1999): 2281-2286.
PMID
10614934
Source
scival
Published In
Biomaterials
Volume
20
Issue
23-24
Publish Date
1999
Start Page
2281
End Page
2286
DOI
10.1016/S0142-9612(99)00158-1

Polymeric biomaterials with degradation sites for proteases involved in cell migration

A new class of biodegradable polymeric biomaterials is described which exhibits degradation by specific enzymes that are localized near cell surfaces during cell migration. These materials are telechelic BAB block copolymers of the water-soluble biocompatible polymer, polyethylene glycol (A block) and short oligopeptide that are cleavage sequences for targeted enzymes (B block). These polymers are further capped at each end with reactive acrylate groups to allow polymerization to form crosslinked hydrogel networks. The combination of two types of bioactive signals, one for cell-mediated degradation, and one for cell adhesion, into one material should achieve a biomemitic polymeric hydrogel with properties of natural extracellular matrix.

Authors
West, JL; Hubbell, JA
MLA Citation
West, JL, and Hubbell, JA. "Polymeric biomaterials with degradation sites for proteases involved in cell migration." Macromolecules 32.1 (1999): 241-244.
Source
scival
Published In
Macromolecules
Volume
32
Issue
1
Publish Date
1999
Start Page
241
End Page
244
DOI
10.1021/ma981296k

Platelet adhesion on a bioresorbable poly(propylene fumarate-co-ethylene glycol) copolymer

Platelet adhesion and aggregation on poly(propylene fumarate-co-ethylene glycol), P(PF-co-EG), hydrogels was examined under both static and flow conditions. Adherent platelets were quantified under static conditions using both 111Indium oxine-labeled platelets as well as a lactate dehydrogenase, LDH, assay. The radiolabeling assay showed a significant decrease in platelet attachment on the copolymer hydrogel films relative to the poly(propylene fumarate), PPF, homopolymer. In addition, there were reductions in adhesion resulting from the increase in poly(ethylene glycol), PEG, weight percent or molecular weight. There was good agreement between both assays under static conditions for the copolymer films. Platelet surface coverage was quantified under flow conditions in a parallel plate flow chamber using the LDH assay. There was a dramatic decrease in the number of adherent platelets on the copolymers relative to glass and silicone rubber controls. All of the copolymer surfaces showed minimal aggregation with no thrombus formation or platelet spreading as assessed qualitatively using scanning electron microscopy. These results suggest that P(PF-co-EG) is a good candidate for development as a cardiovascular implant.

Authors
Suggs, LJ; West, JL; Mikos, AG
MLA Citation
Suggs, LJ, West, JL, and Mikos, AG. "Platelet adhesion on a bioresorbable poly(propylene fumarate-co-ethylene glycol) copolymer." Biomaterials 20.7 (1999): 683-690.
PMID
10208411
Source
scival
Published In
Biomaterials
Volume
20
Issue
7
Publish Date
1999
Start Page
683
End Page
690
DOI
10.1016/S0142-9612(98)00226-9

Surface modification with cell adhesion peptides alters extracellular matrix deposition

The goal of the current study was to evaluate matrix protein synthesis by cells cultured on materials modified with cell adhesion ligands. We examined the effects of surface peptide density and of peptides with different ligand affinities on extracellular matrix production by smooth muscle cells, endothelial cells, and fibroblasts. While initial adhesion was greatest on the higher density peptide surfaces, all cell types exhibited decreased matrix production on the more highly adhesive surfaces. Similarly, when different peptides were evaluated, matrix production was the lowest on the most adhesive surface and highest on the least adhesive surface. These results suggest that extracellular matrix synthesis is regulated, to some extent, by signal transduction initiated by adhesion events. This may pose limitations for use of bioactive materials as tissue engineering scaffolds, since matrix production is an important aspect of tissue formation. However, it may be possible to increase matrix production on highly adhesive surfaces using exogenous factors. TGF-β was shown to increase matrix production by both smooth muscle cells and endothelial cells.

Authors
Mann, BK; Tsai, AT; Scott-Burden, T; West, JL
MLA Citation
Mann, BK, Tsai, AT, Scott-Burden, T, and West, JL. "Surface modification with cell adhesion peptides alters extracellular matrix deposition." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 1 (1999): 94--.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
1
Publish Date
1999
Start Page
94-

Nitric oxide releasing materials for the prevention of thrombosis and restenosis

The goal of the current study was to synthesize biofunctional polymers that spontaneously release nitric oxide under physiological conditions. Such materials may have applications for the prevention of thrombosis and restenosis following arterial injury. We have synthesized two hydrogels that release nitric oxide (NO) with different release kinetics. There was evidence of NO release over a period of several weeks from NO-nucleophile complexes within hydrogels, while S-nitrosocysteine hydrogels displayed NO release over several hours.

Authors
Bohl, KS; West, JL
MLA Citation
Bohl, KS, and West, JL. "Nitric oxide releasing materials for the prevention of thrombosis and restenosis." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 2 (1999): 719--.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
2
Publish Date
1999
Start Page
719-

Mechanical properties of tissue engineered constructs with increased crosslinking of the extracellular matrix

A major issue with tissue engineered vascular grafts has been burst failure due to inadequate mechanical properties of the engineered arterial tissue. Crosslinking and elaboration of extracellular matrix (ECM) proteins are largely responsible for mechanical integrity of vascular tissue. Lysyl Oxidase (LOX) plays a major role in crosslinking elastin and collagen fibers in the ECM. In the current study, we are evaluating the effects of increased LOX activity on the mechanical strength of engineered tissues. Two strains of rat aortic smooth muscle cells, one with two-fold higher LOX expression than the control strain, cultured in 3-dimensional collagen type I lattices were used. Significant differences in Young's Modulus and ultimate tensile strength were found through dynamic mechanical testing.

Authors
Yonter, EO; Scott-Burden, T; West, JL
MLA Citation
Yonter, EO, Scott-Burden, T, and West, JL. "Mechanical properties of tissue engineered constructs with increased crosslinking of the extracellular matrix." Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 1 (1999): 129--.
Source
scival
Published In
Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume
1
Publish Date
1999
Start Page
129-

Growth factor mobilization in vascular wound healing

Intravascular hydrogel barriers were used to separate the injured arterial wall from blood contact, thus preventing interaction with thrombus-derived factors and plasma proteins. The complex cascade of growth factors and cytokines involved in the vascular wound healing process were successfully elucidated.

Authors
West, JL; Mann, BK
MLA Citation
West, JL, and Mann, BK. "Growth factor mobilization in vascular wound healing." American Society of Mechanical Engineers, Bioengineering Division (Publication) BED 42 (1999): 749-750.
Source
scival
Published In
American Society of Mechanical Engineers, Bioengineering Division (Publication) BED
Volume
42
Publish Date
1999
Start Page
749
End Page
750

Nitric oxide producing materials: A potential therapy for thrombosis and restenosis

Authors
Bohl, K; West, J
MLA Citation
Bohl, K, and West, J. "Nitric oxide producing materials: A potential therapy for thrombosis and restenosis." Proceedings of the Controlled Release Society 26 (1999): 56-57.
Source
scival
Published In
Proceedings of the Controlled Release Society
Issue
26
Publish Date
1999
Start Page
56
End Page
57

In situ photopolymerization of PEG-based hydrogels for wound healing applications

Biomaterials can be used to alter wound healing events. In particular, biomaterials serve as scaffolds for cell adhesion and tissue growth, as cell non-adhesive barriers, or as a depots for localized drug delivery. Among the available biomaterials, photopolymerized, PEG-based hydrogels are considered to be the most important.

Authors
West, JL
MLA Citation
West, JL. "In situ photopolymerization of PEG-based hydrogels for wound healing applications." American Society of Mechanical Engineers, Bioengineering Division (Publication) BED 35 (1997): 413--.
Source
scival
Published In
American Society of Mechanical Engineers, Bioengineering Division (Publication) BED
Volume
35
Publish Date
1997
Start Page
413-

In Situ Formation of Polymer Matrices for Localized Drug Delivery

Polymer matrices can be formed within the body in direct contact with cells and tissues by a variety of techniques, both physicochemical and covalent in nature, including thermal gelation, pH-sensitive gelation, the use of thixotropic materials, precipitation from certain organic solutions photopolymerization, and chemical cross-linking. these types of materials can be injected as liquids and converted to a gel or solid in situ. Many of these polymer systems are appropriate for delivery of peptides and proteins.

Authors
West, JL
MLA Citation
West, JL. "In Situ Formation of Polymer Matrices for Localized Drug Delivery." ACS Symposium Series 675 (1997): 119-123.
Source
scival
Published In
ACS Symposium Series
Volume
675
Publish Date
1997
Start Page
119
End Page
123

Polymers for the management of wound healing

Authors
West, JL
MLA Citation
West, JL. "Polymers for the management of wound healing." TRENDS IN POLYMER SCIENCE 4.7 (July 1996): 206-207. (Academic Article)
Source
manual
Published In
Trends in Polymer Science
Volume
4
Issue
7
Publish Date
1996
Start Page
206
End Page
207

Separation of the arterial wall from blood contact using hydrogel barriers reduces intimal thickening after balloon injury in the rat: The roles of medial and luminal factors in arterial healing

The objective of this study was to clarify the relative roles of medial versus luminal factors in the induction of thickening of the arterial intima after balloon angioplasty injury. Platelet-derived growth factor (PDGF) and thrombin, both associated with thrombosis, and basic fibroblast growth factor (bFGF), stored in the arterial wall, have been implicated in this process. To unequivocally isolate the media from luminally derived factors, we used a 20- μm thick hydrogel barrier that adhered firmly to the arterial wall to block thrombus deposition after balloon-induced injury of the carotid artery of the rat. Thrombosis, bFGF mobilization, medial repopulation, and intimal thickening were measured. Blockade of postinjury arterial contact with blood prevented thrombosis and dramatically inhibited both intimal thickening and endogenous bFGF mobilization. By blocking blood contact on the two time scales of thrombosis and of intimal thickening, and by using local protein release to probe, by reconstitution, the individual roles of PDGF-BB and thrombin, we were able to conclude that a luminally derived factor other than PDGF or thrombin is required for the initiation of cellular events leading to intimal thickening after balloon injury in the rat. We further conclude that a luminally derived factor is required for mobilization of medial bFGF.

Authors
West, JL; Hubbell, JA
MLA Citation
West, JL, and Hubbell, JA. "Separation of the arterial wall from blood contact using hydrogel barriers reduces intimal thickening after balloon injury in the rat: The roles of medial and luminal factors in arterial healing." Proceedings of the National Academy of Sciences of the United States of America 93.23 (1996): 13188-13193.
PMID
8917566
Source
scival
Published In
Proceedings of the National Academy of Sciences of USA
Volume
93
Issue
23
Publish Date
1996
Start Page
13188
End Page
13193
DOI
10.1073/pnas.93.23.13188

Efficacy of adhesion barriers: Resorbable hydrogel, oxidized regenerated cellulose and hyaluronic acid

OBJECTIVE: To compare a novel resorbable hydrogel barrier with two previously studied barriers, oxidized regenerated cellulose and hyaluronic acid, for the prevention of postoperative adhesions. STUDY DESIGN: Two models were employed in the rat uterine horn, one of adhesion formation after devascularization and serosal injury and one of adhesion reformation after adhesiolysis. RESULTS: In the devascularization model, hydrogel treatment reduced the mean extent of adhesion formation from 73% in the control group to 13% (P <.005). Hyaluronic acid pretreatment reduced the extent of adhesion formation to 44% (P < .05), while oxidized regenerated cellulose failed to reduce formation (P > .25). In the adhesiolysis model, treatment with the hydrogel reduced the mean extent of adhesion formation from 87% in the control group to 20% (P < .005). Neither the oxidized regenerated cellulose nor the hyaluronic acid treatments lowered the extent of adhesion formation from the control group (P > .25). The hydrogel barrier was observed to be resorbed over a five-day period and remained adherent to the tissue during resorption. CONCLUSION: Resorbable hydrogel barriers are highly effective in the reduction of adhesion formation and reformation in the rat. This is probably due to the good biocompatibility and retention of these materials upon the site of application.

Authors
West, JL; Chowdhury, SM; Sawhney, AS; Pathak, CP; Dunn, RC; Hubbell, JA
MLA Citation
West, JL, Chowdhury, SM, Sawhney, AS, Pathak, CP, Dunn, RC, and Hubbell, JA. "Efficacy of adhesion barriers: Resorbable hydrogel, oxidized regenerated cellulose and hyaluronic acid." Journal of Reproductive Medicine for the Obstetrician and Gynecologist 41.3 (1996): 149-154.
PMID
8778411
Source
scival
Published In
The Journal of reproductive medicine
Volume
41
Issue
3
Publish Date
1996
Start Page
149
End Page
154

Interfacially photopolymerized hydrogels for local vascular drug delivery

An interfacial photopolymerization method for the intravascular application of thin hydrogel barriers was developed. The hydrogels are well suited for localized intravascular delivery of hydrophilic macromolecules dissolved in the aqueous precursor solution and entrapped in the hydrogel after illumination. It was found that when platelet derived growth factor (PDGF) was locally delivered from the photopolymerized hydrogel after vascular injury, the thickness of the intimal layer of the arterial wall increased markedly. A protein can be delivered from a photopolymerized hydrogel while retaining its biological activity and the released protein can permeate through the vessel wall to act upon its target, medial smooth muscle cells.

Authors
West, JL; An, Y; Hubbell, JA
MLA Citation
West, JL, An, Y, and Hubbell, JA. "Interfacially photopolymerized hydrogels for local vascular drug delivery." Transactions of the Annual Meeting of the Society for Biomaterials in conjunction with the International Biomaterials Symposium 1 (1996): 645--.
Source
scival
Published In
Transactions of the Annual Meeting of the Society for Biomaterials in conjunction with the International Biomaterials Symposium
Volume
1
Publish Date
1996
Start Page
645-

Proteolytically degradable hydrogels

Authors
West, JL; Hubbell, JA
MLA Citation
West, JL, and Hubbell, JA. "Proteolytically degradable hydrogels." Proceedings of the Controlled Release Society 23 (1996): 224-225.
Source
scival
Published In
Proceedings of the Controlled Release Society
Issue
23
Publish Date
1996
Start Page
224
End Page
225

Photopolymerized intravascular hydrogels for protein delivery

Authors
West, JL; An, Y; Hubbell, JA
MLA Citation
West, JL, An, Y, and Hubbell, JA. "Photopolymerized intravascular hydrogels for protein delivery." Proceedings of the Controlled Release Society 23 (1996): 833-834.
Source
scival
Published In
Proceedings of the Controlled Release Society
Issue
23
Publish Date
1996
Start Page
833
End Page
834

POLYMERS IN MEDICINE - MANIPULATING WOUND-HEALING

Authors
WEST, JL; HERN, D; HUBBELL, JA
MLA Citation
WEST, JL, HERN, D, and HUBBELL, JA. "POLYMERS IN MEDICINE - MANIPULATING WOUND-HEALING." ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY 210 (August 1995): 222-PMSE. (Academic Article)
Source
manual
Published In
ACS National Meeting Book of Abstracts
Volume
210
Publish Date
1995
Start Page
222
End Page
PMSE

BLOOD CONTACT IS NECESSARY FOR INTIMAL THICKENING, MEDIAL REPOPULATION, AND LIBERATION OF MEDIAL BASIC FIBROBLAST GROWTH-FACTOR IN THE RAT - INVESTIGATION WITH HYDROGEL BARRIERS

Authors
HUBBELL, JA; WEST, JL
MLA Citation
HUBBELL, JA, and WEST, JL. "BLOOD CONTACT IS NECESSARY FOR INTIMAL THICKENING, MEDIAL REPOPULATION, AND LIBERATION OF MEDIAL BASIC FIBROBLAST GROWTH-FACTOR IN THE RAT - INVESTIGATION WITH HYDROGEL BARRIERS." THROMBOSIS AND HAEMOSTASIS 73.6 (June 1995): 1350-1350. (Academic Article)
Source
manual
Published In
Thrombosis and haemostasis
Volume
73
Issue
6
Publish Date
1995
Start Page
1350
End Page
1350

NOVEL POLYMERS FOR THE DELIVERY OF PEPTIDES, OLIGONUCLEOTIDES AND PROTEINS

Authors
HUBBELL, JA; WEST, JL; CHOWDHURY, SM; DUNN, RC
MLA Citation
HUBBELL, JA, WEST, JL, CHOWDHURY, SM, and DUNN, RC. "NOVEL POLYMERS FOR THE DELIVERY OF PEPTIDES, OLIGONUCLEOTIDES AND PROTEINS." JOURNAL OF CELLULAR BIOCHEMISTRY (January 1995): 167-167. (Academic Article)
Source
manual
Published In
Journal of Cellular Biochemistry
Publish Date
1995
Start Page
167
End Page
167

Photopolymerized hydrogel materials for drug delivery applications

A novel photopolymerized hydrogel material has been developed for use as a drug delivery vehicle for bioactive materials. The hydrogel precursor consists of polyethylene glycol copolymerized with an α-hydroxy acid and with acrylate termini at each end. The precursor is water-soluble and non-toxic. The precursor polymerization conditions are very mild, and polymerization can be carried out in direct contact with cells and tissues. The degradation rate and permeability of the hydrogel can be altered by changing the composition of the precursors, allowing use of this class of materials for a variety of applications. In vitro release of proteins and oligonucleotides is reported. © 1995.

Authors
West, JL; Hubbell, JA
MLA Citation
West, JL, and Hubbell, JA. "Photopolymerized hydrogel materials for drug delivery applications." Reactive Polymers 25.2-3 (1995): 139-147.
Source
scival
Published In
Reactive and Functional Polymers
Volume
25
Issue
2-3
Publish Date
1995
Start Page
139
End Page
147

Comparison of covalently and physically cross-linked polyethylene glycol-based hydrogels for the prevention of postoperative adhesions in a rat model

A covalently and a physicochemically cross-linked hydrogel, both based primarily on polyethylene glycol and both formed in situ, were compared side by side in a rat uterine horn devascularization and serosal injury model for efficacy in adhesion prevention. The primary difference between the two materials was the nature of their cross-linking. The covalently cross-linked hydrogel was a photopolymerized polyethylene glycol-co-lactic acid diacrylate, and the physically cross-linked hydrogel was a polyethylene glycol-co-polypropylene glycol, Poloxamer 407®. In the surgical model employed, application of the covalently cross-linked hydrogel reduced the extent of adhesion formation from 75 ± 10% in the control group to 16 ± 6% (mean ± s.d., P < 0.001). Application of the physically crosslinked hydrogel reduced adhesion formation to 38 ± 19% (P < 0.01). Retention of the two hydrogels upon the site of application was also evaluated. The covalently cross-linked hydrogel formed a continuous barrier upon the uterine horns for more than 4 d, while the physicochemically cross-linked hydrogel was present upon the uterine horns for less than 2 d. This difference in retention was probably the cause of the difference in efficacy and may be attributed to the nature of the cross-linking.

Authors
West, JL; Hubbell, JA
MLA Citation
West, JL, and Hubbell, JA. "Comparison of covalently and physically cross-linked polyethylene glycol-based hydrogels for the prevention of postoperative adhesions in a rat model." Biomaterials 16.15 (1995): 1153-1156.
PMID
8562791
Source
scival
Published In
Biomaterials
Volume
16
Issue
15
Publish Date
1995
Start Page
1153
End Page
1156
DOI
10.1016/0142-9612(95)93579-3

Localized intravascular protein delivery from photopolymerized hydrogels

Authors
West, JL; Hubbell, JA
MLA Citation
West, JL, and Hubbell, JA. "Localized intravascular protein delivery from photopolymerized hydrogels." Proceedings of the Controlled Release Society 22 (1995): 17-18.
Source
scival
Published In
Proceedings of the Controlled Release Society
Issue
22
Publish Date
1995
Start Page
17
End Page
18

ION DRIVE TECHNOLOGY READINESS FOR 1985 HALLEY COMET RENDEZVOUS MISSION

Authors
WEST, JL
MLA Citation
WEST, JL. "ION DRIVE TECHNOLOGY READINESS FOR 1985 HALLEY COMET RENDEZVOUS MISSION." ASTRONAUTICS \& AERONAUTICS 16.12 (1978): B18-B18. (Academic Article)
Source
manual
Published In
Astronautics and Aeronautics
Volume
16
Issue
12
Publish Date
1978
Start Page
B18
End Page
B18
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