Multifunctional calcium phosphate-bioactive glass composite cement with controlled degradation and local antibiotic delivery for bone regeneration.

Critical-sized bone defects in infection-prone clinical environments demand multi-functional biomaterials that can synchronously provide temporary defect filling and structural support in non-load-bearing applications, localised antibacterial shielding, and active biological remodelling. In this study, we developed an injectable, multi-functional composite bone cement by blending 50 wt% of highly mesoporous 58S bioactive glass (BG) into a calcium phosphate cement (CPC) matrix, functionalised via an optimised HPO42-/citric acid liquid phase and local antibiotic loading. Our optimised composite successfully overcame the traditional handling and washout limitations of highly glass-loaded cements, achieving a manageable final setting time of 23 ± 1.5 min and controlled structural degradation that stabilises at approximately 50%. The incorporation of mesoporous BG was associated with sustained, pseudo-Fickian release of vancomycin and ceftazidime over 28 days. The release behaviour may be influenced by progressive BG dissolution together with diffusion through the hydrated composite matrix. In vitro, the ionic-alkaline microenvironment and sustained drug delivery provided robust antibacterial protection against Escherichia coli and Staphylococcus aureus without altering bone marrow stromal cell cytocompatibility or alkaline phosphatase expression. Finally, an in vivo critical-sized rat cranial defect model confirmed that the composite achieves uniform, accelerated bone regeneration and substantial defect closure within 8 weeks. Together, these findings demonstrate that this degradation-associated delivery framework represents a promising strategy for managing complex, infection-prone bone defects.