Antibacterial sequential growth factor delivery from alginate/gelatin methacryloyl microspheres for bone regeneration

Autologous or allogeneic bone tissue grafts remain the mainstay of treatment for clinical bone defects. However, the risk of infection and donor scarcity in bone grafting pose challenges to the process. Therefore, the development of excellent biomaterial grafts is of great clinical importance for the repair of bone defects. In this study, we used gas-assisted microfluidics to construct double-cross-linked hydrogel microspheres with good biological function based on the ionic cross-linking of Cu2+ with alginate and photo-cross-linking of gelatin methacryloylamide (GelMA) by loading vascular endothelial growth factor (VEGF) and His-tagged bone morphogenetic protein-2 (BMP2) (AGMP@VEGF&BMP2). The Cu2+ component in the microspheres showed good antibacterial and drug-release behavior, whereas VEGF and BMP2 effectively promoted angiogenesis and bone tissue repair. In in vitro and in vivo experiments, the dual cross-linked hydrogel microspheres showed good biological function and biocompatibility. These results demonstrate that AGMP@VEGF&BMP2 microspheres could be used as a bone defect graft substitute to promote effective healing of bone defects and may be applied to other tissue engineering studies.