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

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-NH2) 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-NH2. SiPc-NH2 as a "structural stabilizer" of BP nanosheets reconstructed well-dispersed BP-SiPc-NH2 nanosheets, which improves the biocompatibility of BP, reduces oxidation and enhances photothermal conversion, guaranteeing osteogenic and antimicrobial properties. Furthermore, findings show BP-SiPc-NH2-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-NH2 strategy holds great promise for bone repair applications.