Zinc-Doped Black Phosphorus Nanosheets Integrated into Janus Stratified Structural Hydrogel for Vascularized Bone Regeneration

Bone tissue regeneration is a dynamic process in which osteogenesis and angiogenesis are closely linked. Vascular reconstruction and invasion have positive significance in restoring blood supply and remodeling of bone formation. For different types of bone defects, previous studies tended to focus on the formation of bone tissue, but neglected the regeneration and reconstruction of blood vessels. In the present study, a Janus-structured bilayer hydrogel was constructed, in which the upper layer promotes the formation of early osteogenic vascular network by doping zinc-doped black phosphorus nanosheets (BP@Zn) into methacryloyl gelatin/methacryloyl hyaluronic acid (GelMA/HAMA), and the added β-tricalcium phosphate (β-TCP) in the lower layer can be used to maintain the local stability and promote bone regeneration. The two-dimensional nanosheets and metal ions formed by the gradual degradation of BP@Zn can promote the migration, adhesion, and tubular structure formation of vascular endothelial cells, and the role of β-TCP is quite significant in the biomineralization process. In the cranial defect model, GelMA/HAMA/BP@Zn is also shown to be effective in promoting vascularization and bone regeneration. Overall, this study provides a promising strategy for the treatment of bone defects.