A dual-bioeffect nanoengineered piezoelectric-photothermal hydrogel induces endochondral ossification and promotes critical-sized bone regeneration

INTRODUCTION: Critical-sized bone defects remain a major clinical challenge in orthopedics. Current strategies including inert implants and autologous bone grafts suffer from complications like loosening, infection, and donor site morbidity. Piezoelectric and photothermal stimuli synergistically regulate bone regeneration, and black phosphorus nanosheets (BPNSs) possess both effects and biodegradability, but are prone to oxidation and aggregation. OBJECTIVES: This study aims to develop an injectable biomimetic hydrogel with dual piezoelectric-photothermal bioeffects for minimally invasive and efficient repair of irregular critical-sized bone defects. METHODS: BPNS@rhCOL1MA composite system was constructed by embedding BPNSs into recombinant human methacrylated type I collagen hydrogel. Physicochemical characterization, in vitro cell assays, transcriptomic analysis, and in vivo validation in a rabbit rib defect model were performed. RESULTS: The material exhibited stable network, injectability, and controllable dual-responsive properties. It significantly enhanced osteogenic differentiation of BMSCs in vitro. Transcriptomics revealed activation of electrical/thermal signal transduction and angiogenesis pathways. In vivo, it markedly improved new bone formation, bone mineral density, and mechanical properties. CONCLUSION: This work first integrates the dual bioeffects of BPNSs with injectable human-derived collagen hydrogel, providing a novel strategy for minimally invasive repair of irregular bone defects.