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

Date
2017-06
Authors
Schweller, Ryan M
Wu, Zi Jun
Klitzman, Bruce
West, Jennifer L
Repository Usage Stats
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Abstract
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.
Type
Journal article
Subject
Angiogenesis
Endothelial cell
Inflammation
Mechanical properties
Permalink
https://hdl.handle.net/10161/15360
Published Version (Please cite this version)
10.1007/s10439-017-1822-8
Publication Info
Schweller, Ryan M; Wu, Zi Jun; Klitzman, Bruce; & West, Jennifer L (2017). Stiffness of Protease Sensitive and Cell Adhesive PEG Hydrogels Promotes Neovascularization In Vivo. Ann Biomed Eng, 45(6). pp. 1387-1398. 10.1007/s10439-017-1822-8. Retrieved from https://hdl.handle.net/10161/15360.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Klitzman

Bruce Klitzman

Associate Professor Emeritus in Surgery
Our overriding interests are in the fields of tissue engineering, wound healing, biosensors, and long term improvement of medical device implantation. My basic research interests are in the area of physiological mechanisms of optimizing substrate transport to tissue. This broad topic covers studies on a whole animal, whole organ, hemorheological, microvascular, cellular, ultrastructural, and molecular level. The current projects include: 1) control of blood flow and flow distribu
West

Jennifer L West

Fitzpatrick Family University Distinguished Professor of Engineering
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.
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