Hypoxia regulates BG/BMSCs@GelMA bioactive scaffolds to promote angiogenesis, osteogenesis and regulate immune responses for bone regeneration

[Display omitted] •The DFO-PLGA nanospheres slowly release DFO and reduce biotoxicity.•DFO-PLGA nanospheres promoted the osteogenic differentiation of BMSCs in the scaffold and co-cultured BMSCs.•The scaffold promotes angiogenesis by releasing DFO to activate the HIF-1α pathway.•The hypoxia regulated scaffold has the properties of immunoregulation, angiogenesis and osteoinduction.•The hypoxia regulated scaffold showed significant bone regeneration performance 8 weeks after implantation. In the aging society, bone defects significantly threaten human health. Therefore, several biomaterials have been developed to promote bone regeneration. However, previous studies have predominantly focused on optimizing the osteoinductive capacity of materials while neglecting vascular regeneration and immune responses elicited by biomaterials. The repair of bone defects is a complex biological process that involves not only bone resorption and formation, but also inflammation, immunity, and vascularization. The present study successfully encapsulated deferoxamine (DFO) into poly (lactic-co-glycolic acid) (PLGA) to form nanospheres for the sustained release of DFO, thereby simulating a hypoxic microenvironment. DFO-PLGA/Bioactive glass (BG)/Bone marrow mesenchymal stem cells (BMSCs) @GelMA (DBB@GelMA) exhibited excellent biocompatibility and osteoinductive properties in vitro. Furthermore, DBB@GelMA continuously releases DFO to promote vascular regeneration, M2 polarization of macrophages, and osteogenic differentiation of BMSCs. The finding from the experiment on SD rat calvarial defect repair further validated its exceptional immunoregulatory, angiogenic, and osteoinductive capabilities. In conclusion, this composite hydrogel offers a novel strategy for regulating the hypoxic microenvironment and holds promise for bone-defect repair.