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

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2017-06

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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.

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10.1007/s10439-017-1822-8

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Schweller, Ryan M, Zi Jun Wu, Bruce Klitzman and Jennifer L West (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.

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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 distribution in the microcirculation,
2) the effects of long-term synthetic and biologic implants on substrate transport to tissues,
3) tissue engineering; combining isolated cells, especially adult stem cells, with biomaterials to form specialized composite structures for implantation, with particular emphasis on endothelial cell physiology and its alteration by isolation and seeding on biomaterials.
4) decreasing the thrombogenicity of synthetic blood vessels and other blood-contacting devices, and improving their overall performance and biocompatibility.
5) reducing tissue damage resulting from abnormal perfusion (e.g., relative ischemia, anoxia, etc.) and therapies which minimize ischemic damage.
6) biosensor function, particularly glucose sensors in normal and diabetics.
7) measurement of tissue blood flow and oxygenation as an indicator of tissue viability and functional potential.
8) development of biocompatible materials for soft tissue reconstruction or augmentation.
9) improving performance of glaucoma drainage devices by directing a more favorable foreign body reaction
10) wound healing; particularly internal healing around foreign materials and the effect and prevention of microbes around implanted devices.


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