Synergistic 3D-bioprinted scaffold with multi-level adaptability for vascularized bone regeneration via osteogenesis-angiogenesis coupling

3D bioprinting enables the fabrication of biomimetic, cell-laden and pro-osteogenic constructs with high precision for bone regeneration. The ability of integrating favourable mechanical strength and multi-material interactive bioactivity in engineered constructs for efficient bone defect repair is still a challenge. Herein, we employed a dual-nozzle synergistic 3D bioprinting technology to fabricate a biocomposite scaffold that integrated interactive soft hydrogel filaments and hard polycaprolactone (PCL)-based filaments by mimicking weave patterns. The multi-material scaffold design aimed at providing features of suitable microstructure and long-term mechanical support, enhanced vascularized bone regeneration for bone repair. Chitosan/hyaluronic acid functionalized mesoporous silica nanoparticles bearing osteogenic protein on the surface and angiogenic drug in the pores were embedded into cell-supportive hydrogel bioink for promoting osteogenesis-angiogenesis coupling. Meanwhile, MgO nanoparticles were incorporated into structure-supportive PCL matrix for improving mechanical strength and compensating angiogenic/osteogenic activities by sustained release of Mg 2+ . The biocomposite scaffold had good cytocompatibility, and could stimulate in vitro angiogenic behavior and osteogenic differentiation. In vivo experiments revealed that the biocomposite scaffolds significantly enhanced vascularization and promoted bone regeneration on the cranial defect model. Overall, this study has offered a promising strategy for fabricating a multi-level adaptable 3D-bioprinted scaffold for bone defect repair through osteogenesis-angiogenesis coupling. • A soft/hard hybrid scaffold was constructed by utilizing dual-nozzle synergistic 3D bioprinting. • The hybrid scaffold showed interconnected pore structure and favorable mechanical strength. • Osteogenesis-angiogenesis coupling was achieved by cooperative effect of multi-factors integration. • Multi-level adaptable 3D-bioprinted scaffold was fabricated for vascularized bone regeneration