Black phosphorus-loaded mineralized UV-responsive chitosan hydrogel for enhanced osteogenesis and antibacterial activity

Abstract Favorable osteogenesis and effective antibacterial activity are two essential requirements for ideal scaffolds in bone tissue engineering, particularly for infected bone defects. Herein, we developed a novel hydrogel system based on mineralized ultraviolet-responsive methacrylated chitosan hydrogel (CSMA) integrated with black phosphorus (BP) nanosheets exhibiting a photothermal effect. BP was incorporated into CSMA and subsequently subjected to in situ biomineralization to form a BP-loaded mineralized hydrogel (BP@CSMA/CaCO3). The physicochemical and biological properties of BP@CSMA/CaCO3 were systematically investigated in vitro. BP incorporation and CaCO3 mineralization improved hydrogel stability and enabled sustained Ca2+ and phosphorus ion release, thereby supporting an osteogenesis-favorable microenvironment. Under high-intensity near-infrared (NIR) irradiation, BP-containing hydrogels exhibited strong antibacterial activity, which was supported by both photothermal heating and singlet oxygen generation. Under mild NIR stimulation, BP@CSMA/CaCO3 promoted bone mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation, with increased ALP activity and osteogenic gene expression. Transcriptomic analysis further suggested the involvement of cytoskeletal and immune-related regulation in the enhanced osteogenic response. The application of BP@CSMA/CaCO3 in a calvarial defect model (in vivo) indicated its superior bone formation ability. These findings suggested that BP@CSMA/CaCO3 integrated antibacterial activity, ion-mediated osteogenic support and NIR-responsive regulation had great potential for bone regeneration.