Abstract

Background Regeneration of osteoporotic bone defects is a major clinical challenge due to impaired osteogenic activity and high infection risks. We developed an injectable rhBMP-2-loaded calcium phosphate cement (CPC) and chitosan (CH) composite hydrogel (rhBMP-2/CPC@CH) to evaluate its therapeutic efficacy for repairing osteoporotic bone defects. Methods The rhBMP-2/CPC@CH hydrogel was synthesized and characterized for its physicochemical properties and enzymatic degradation. Its osteogenic potential was assessed using BMSCs. An OVX-induced rat cranial defect model was established to evaluate in vivo bone repair via Micro-CT and histological analysis. Antibacterial activity and effects on wound healing were also investigated. Results The rhBMP-2/CPC@CH hydrogel exhibited excellent injectability, self-healing, and enzymatic degradation properties with a uniform elemental distribution. The hydrogel significantly promoted the osteogenic differentiation of BMSCs, as evidenced by increased ALP activity and mineralized nodule formation. In the OVX-induced rat model, Micro-CT and histological analysis demonstrated that the hydrogel significantly increased bone mineral density and bone volume fraction, leading to dense new bone formation. Furthermore, the hydrogel effectively inhibited the growth of S. aureus and E. coli without adverse effects on wound healing, establishing a protected regenerative microenvironment. Conclusions The rhBMP-2/CPC@CH hydrogel accelerates the repair of osteoporotic bone defects by providing an osteoinductive microenvironment and intrinsic antibacterial defense, representing a promising minimally invasive strategy for clinical bone regeneration.