Bioconjugation of a Collagen-Mimicking Peptide Onto Poly(vinyl alcohol) Encourages Endothelialization While Minimizing Thrombosis

胶原蛋白模拟肽与聚乙烯醇的生物共轭促进内皮化,同时最大限度地减少血栓形成

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作者:Novella M Bates, Heather E Heidenreich, Meghan E Fallon, Yuan Yao, Evelyn K F Yim, Monica T Hinds, Deirdre E J Anderson

Abstract

Poly(vinyl alcohol) hydrogel, PVA, is a suitable material for small-diameter vascular grafting. However, the bioinert properties of the material do not allow for in situ endothelialization, which is needed to combat common graft failure mechanisms, such as intimal hyperplasia and thrombosis. In this work, the surface of planar and tubular PVA was covalently modified with a collagen-mimicking peptide, GFPGER. The surface of modified PVA was characterized by measuring contact angle and x-ray photoelectron spectroscopy. Endothelial cell attachment to GFPGER-modified PVA was quantified and qualitatively examined using immunohistochemical staining. Then, in vitro hemocompatibility testing was performed by quantifying platelet attachment, coagulation factor XII activation, and initiation of fibrin formation. Finally, an established ex vivo, non-human primate model was employed to examine platelet attachment and fibrin formation under non-anticoagulated, whole blood flow conditions. GFPGER-modified PVA supported increased EC attachment. In vitro initiation of fibrin formation on the modified material was significantly delayed. Ex vivo thrombosis assessment showed a reduction in platelet attachment and fibrin formation on GFPGER-modified PVA. Overall, GFPGER-modified PVA encouraged cell attachment while maintaining the material's hemocompatibility. This work is a significant step toward the development and characterization of a modified-hydrogel surface to improve endothelialization while reducing platelet attachment.

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