Methacrylated gelatin and platelet-rich plasma based hydrogels promote regeneration of critical-sized bone defects

Physiological repair of large-sized bone defects requires instructive scaffolds with appropriate mechanical properties,biocompatibility,biodegradability,vasculogenic ability and osteo-inductivity.The objective of this study was to fabricate in situ injectable hydrogels using platelet-rich plasma(PRP)-loaded gelatin methacrylate(GM)and employ them for the regeneration of large-sized bone defects.We performed various biological assays as well as assessed the mechanical properties of GM@PRP hydrogels alongside evaluating the release kinetics of growth factors(GFs)from hydrogels.The GM@PRP hydrogels manifested sufficient mechanical properties to support the filling of the tissue defects.For biofunction assay,the GM@PRP hydrogels significantly improved cell migration and angiogenesis.Especially,transcriptome RNA sequencing of human umbilical vein endothelial cells and bone marrow-derived stem cells were performed to delineate vascularization and biomineralization abilities of GM@PRP hydrogels.The GM@PRP hydrogels were subcutaneously implanted in rats for up to 4 weeks for preliminary biocompatibility followed by their transplantation into a tibial defect model for up to 8 weeks in rats.Tibial defects treated with GM@PRP hydrogels manifested significant bone regeneration as well as angiogenesis,biomineralization,and collagen deposition.Based on the biocompatibility and biological function of GM@PRP hydrogels,a new strategy is provided for the regenerative repair of large-size bone defects.