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In Situ SVVYGLR Peptide Conjugation into Injectable Gelatin-Poly(ethylene glycol)-Tyramine Hydrogel via Enzyme-Mediated Reaction for Enhancement of Endothelial Cell Activity and Neo-Vasculariza
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文摘
Tissue engineering therapies require biocompatible and bioactive biomaterials that are capable of encouraging an angiogenic response for effective tissue regeneration. In this study, a SVVYGLR peptide, which functions as a potent angiogenic factor, was conjugated into injectable gelatin鈥損oly(ethylene glycol)鈥搕yramine (GPT) hydrogels in situ to enhance endothelial cell activities and neo-vascularization. SVVYGLRGGY (SV鈥揧) conjugated GPT (SV鈥揋PT) hydrogels were formed in situ via enzyme-mediated reaction using horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). The physico鈥揷hemical properties were characterized and could be controlled depending on the feed peptide and H2O2 concentration. The concentration of conjugated peptide ranged from 0.37 to 0.81 渭mol/mL, and the elastic moduli (G鈥? of the hydrogels were 600鈥?900 Pa. In vitro cell studies using human umbilical vein endothelial cells (HUVECs) and in vivo subcutaneous injection studies were performed to confirm the effect of the SVVYGLR peptide on HUVEC activity and neo-vascularization. Obtained results demonstrated that the in situ conjugation of SVVYGLR sequences into phenol residues of GPT hydrogels enhanced the activity of HUVECs in vitro and stimulated the formation of new blood vessels in the hydrogel matrices in vivo. From the results, we suggest that in situ conjugation of SV鈥揧 to GPT hydrogels via the enzymatic reaction may be an efficient tool to prepare injectable bioactive hydrogels that can enhance endothelial cell activities and promoting angiogenesis for tissue regeneration.

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