Dual‐Functional Injectable Photothermal Nanohydrogel Promotes Anti‐Inflammation and Bone Regeneration in Distraction Osteogenesis

Large bone defects regularly result in prolonged pain and functional impairment in patients, providing a considerable challenge in medical treatment. Current research in biomaterials for bone defect repair is increasingly centered on integrating osteogenic performance with antibacterial properties inside nanomaterials. In this study, a biomimetic hydrogel with an osteogenic microenvironment is developed primarily based on 2D black phosphorus (BP) nanosheets incorporated into poly-amino acid calcium alginate. Compared to methods using black phosphorus alone, this BP@L-lysine-Polyglutamic acid calcium alginate gel hydrogel (BP@CALG) exhibits reduced cytotoxicity, enhanced mechanical stability, and superior antibacterial properties, thereby synergistically augmenting its osteogenic potential and antibacterial efficacy. Through near-infrared (NIR) irradiation, the hydrogel's osteoinductive and antibacterial abilities are further optimized by means of controllable photothermal activation. Notably, BP@CALG demonstrates immunomodulatory capabilities that facilitate osteogenesis through macrophage polarization. By steering M0 macrophages toward the regenerative M2 phenotype and simultaneously inhibiting pro-inflammatory M1 differentiation, the scaffold effectively controls excessive inflammation. This dual mechanism promotes bone regeneration both directly through osteogenic signaling pathways and indirectly via immune microenvironment regulation.