Black phosphorus-based photothermal-responsive hydrogel enhanced osteoporotic bone injury regeneration by alleviating oxidative stress and remodeling bone homeostasis

Diabetes-induced osteoporosis significantly elevates the risk of fracture-related disability and mortality. Developing effective therapeutic strategies for diabetic-related bone defects has become a pressing concern in both clinical and research domains. This study innovatively constructs a near-infrared light-responsive (NIR) intelligent hydrogel system (carboxymethyl chitosan/gelatin/black phosphorus@bFGF, CG/BPb), utilizing carboxymethyl chitosan and gelatin as the matrix while integrating polydopamine (PDA)-functionalized black phosphorus nanosheets (BP@PDA) as a controlled-release carrier for basic fibroblast growth factor (bFGF). The CG/BPb hydrogel demonstrated remarkable mechanical strength (up to 25 kPa compressive stress at 55% strain) and antioxidant capacity, scavenging 81.1% of ROS and 83.3% of hydroxyl radicals. Under NIR irradiation (1 W/cm², 5 min), the hydrogel achieved a stable photothermal temperature of 42 ± 1 °C, enabling controlled release of bFGF (60% cumulative release within 20 min at pH 6.5) and phosphate ions. In vitro, assessments revealed that the hydrogel enhanced osteoblast viability by 85% in scratch assays and upregulated osteogenic genes (ALP, Runx2, and OCN). Additionally, it also promoted M2 macrophage polarization (increased CD206, decreased iNOS) and suppressed osteoclast activity via NFATc1 and MAPK pathways. In vivo, in a diabetic rat calvarial defect model, the CG/BPb + NIR group showed significant bone regeneration, with increases in bone volume fraction (BV/TV) and bone mineral density (BMD), alongside enhanced vascularization (elevated CD31/CD34/α-SMA expression). This innovative strategy, grounded in material design and synergistic biological functions, not only provides a new solution for the treatment of diabetic bone defects but also promotes technological progress in the field of bone tissue engineering, with substantial academic value and practical applications.