In Situ Crosslinkable Gelatin Hydrogels for Vasculogenic Induction and Delivery of Mesenchymal Stem Cells

摘要: Clinical trials utilizing mesenchymal stem cells (MSCs) for severe vascular diseases have highlighted the need to effectively engraft and promote pro-angiogenic activity. A functional material accomplishing these two goals is an ideal solution as spatiotemporal batch-to-batch variability in classical therapeutic delivery can be minimized, tissue regeneration would begin rapidly at implantation site. Gelatin may serve a promising biomaterial due its excellent biocompatibility, biodegradability, non-immuno/antigenicity. However, dissolution of gelatin body temperature quick enzymatic degradation vivo limited use thus far. To overcome challenges, injectable, situ crosslinkable was developed by conjugating enzymatically-crosslinkable hydroxyphenyl propionic acid (GHPA). When MSCs are cultured 3D vitro or injected GHPA, spontaneous endothelial differentiation occurs, evidenced marked increases endothlelial cell marker expressions (Flk1, Tie2, ANGPT1, vWF) addition forming extensive perfusable network after 2-week subcutaneous implantation. Additionally, favorable host macrophage response achieved with GHPA shown decreased iNOS increased MRC1 expression. These results indicate soluble factor-free template which induces robust neovasculature formation response.