Vascularized and neuralized bone regeneration using injectable double-network cross-linked scaffolds with fully biomimetic organic and biomineralized microenvironments

text. At present, reliable and effective therapeutic strategies for physiological bone regeneration are lacking. In this study, a novel injectable double-network cross-linked scaffold with fully biomimetic organic and biomineralized microenvironments for vascularized and neuralized bone regeneration was designed. Our design involved a dual-network collagen organic framework scaffold (COL1/3) with a ratio based on the natural bone composition. Subsequently, the optimal concentration (4 %) of COL1/3 scaffold for osteogenesis was determined on the basis of its efficiency in subcutaneous bone regeneration. In addition, 2 % multiple native bone inorganic salts were integrated into the COL1/3 scaffold to create a biomimetic biomineralized microenvironment. Consequently, double-network cross-linked scaffolds with a fully biomimetic organic and biomineralized microenvironment were successfully fabricated. Furthermore, in vitro studies showed that the scaffold exhibited good biocompatibility and promoted the secretion of bone-specific proteins while upregulating the expression level of osteogenic genes involved in bone microtissues formation. Finally, in vivo studies on rabbit skull defect repair indicated that the current repair strategy could enhance vascularized and neuralized bone regeneration.