Composite antibiotic-loaded nano-platelet vesicle and mineralized hydrogel system for the treatment of infected bone defects.

Abstract

Complex bone infections are challenging to treat clinically because of their high incidence, recalcitrance, and tendency to recur, with Staphylococcus aureus (S. aureus) being the predominant pathogen. The infection microenvironment disrupts the osteoclast-osteoblast balance, leading to progressive bone loss and posing a major therapeutic challenge. Conventional treatment strategies limited to antibiotics or bone grafts often fail because of issues such as biofilm persistence or a lack of osteoinductive activity. Therefore, highly effective and precise treatment strategies for infected bone defects are urgently needed. In this study, an integrated system combining gentamicin-loaded nano-platelet vesicles (NPVs) with a calcium phosphate (CaP)-mineralized hydrogel was developed. The NPVs serve as effective antibiotic carriers to aid in the elimination of bacteria and reduction in bacterial-induced osteoclast overactivation. Furthermore, the CaP component in the mineralized hydrogel significantly promoted the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Transcriptomic analysis and experimental validation confirmed that the composite hydrogel promoted osteogenic differentiation of BMSCs through activation of the Wnt/β-catenin signalling pathway. Together, this composite platform provides efficient antibacterial activity, suppresses excessive osteoclast activation, and promotes osteogenic differentiation, as validated in an infected bone defect model. Through multimodal synergy, the system enables effective drug delivery, reliable infection control, and bone microenvironment modulation, offering a comprehensive therapeutic strategy for bone infections.