Improved Black Phosphorus Nanocomposite Hydrogel for Bone Defect Repairing: Mechanisms for Advancing Osteogenesis

Abstract Bone defects caused by fractures and diseases often do not heal spontaneously. They require external agents for repair and regeneration. Bone tissue engineering is emerging as a promising alternative to traditional therapies like autografts and allografts. Nanobiomaterials enhance osteoblast resistance to harsh environments by promoting cell differentiation. Black phosphorus (BP), a novel 2D material in biomedicine, displays unique osteogenic and antimicrobial properties. However, BP nanosheets still face clinical limitations like rapid degradation and high‐dose cytotoxicity. To address these, the introduction of amino‐silicon phthalocyanine (SiPc‐NH 2 ) is investigated to see if it can enhance BP dispersion, reduce BP oxidation, and improve stability and safety for better osteogenesis and antibacterial effects through noncovalent interactions (van der Waals, π–π stacking and electrostatic interactions). Here, the self‐healing hydrogel is successfully designed using a step‐by‐step co‐assembly of BP and SiPc‐NH 2. SiPc‐NH 2 as a “structural stabilizer” of BP nanosheets reconstructed well‐dispersed BP‐SiPc‐NH 2 nanosheets, which improves the biocompatibility of BP, reduces oxidation and enhances photothermal conversion, guaranteeing osteogenic and antimicrobial properties. Furthermore, findings show BP‐SiPc‐NH 2 ‐induced mitochondrial changes support osteogenesis by regulating the crosstalk between Hippo and Wnt signaling pathways‐mediated mitochondrial homeostasis, and boosting cellular bioenergetics. Overall, this mitochondrial morphology‐based BP‐SiPc‐NH 2 strategy holds great promise for bone repair applications.