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Stiffness of Protease Sensitive and Cell Adhesive PEG Hydrogels Promotes Neovascularization In Vivo.
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 articlePermalink
https://hdl.handle.net/10161/15360Published Version (Please cite this version)
10.1007/s10439-017-1822-8Publication 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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Show full item recordScholars@Duke
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
Jennifer L West
Adjunct Professor of Biomedical 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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