Vascular endothelial growth factor (VEGF) and endogenous calcium-capturing gelatin methacrylate hydrogels promote bone tissue regeneration

The regeneration of irregular-shaped bone defects remains a perpetuating challenge. Scaffolds with osteogenesis and angiogenesis dual capabilities hold considerable promise for bone tissue repair. The objective of this study was to delineate the synergistic effect of calcium ions (Ca²⁺)-recruiting peptide (FVDVT, abbreviated as CP) and vascular endothelial growth factor (VEGF)-binding prominin-1-derived peptide (DRVQRQTTTVVA, abbreviated as BP) in gelatin methacrylate (GM)-based hydrogels (GM@BCP). BP-loaded hydrogels can recruit VEGF in situ to promote angiogenesis, as well as promote cell viability and growth as revealed by the whole transcriptome RNA sequencing of human umbilical vein endothelial cells (HUVECs). PLA/G@CP short fibers can induce bone matrix mineralization and regulate mechanical behavior of hydrogels. The GM@BCP hydrogels were found to be cytocompatible, non-toxic, and bioresorbable, as well as fill an irregular-shaped bone defect in vivo. Moreover, evaluation in a rat calverial defect model manifested significant promise of GM@BCP hydrogels to promote bone tissue repair by simultaneously inducing osteogenesis and angiogenesis 8 weeks post-operatively. Taken together, our approach of simultaneously harnessing in situ calcium ion (Ca²⁺) binding and VEGF recruitment may have broad implications for fracture repair and potentially other related disciplines.