Neuralized and vascularized fast bone regeneration using recombinant humanized type 1 collagen and native bone composite inorganic salts

Bone injury is a prevalent condition in clinical therapy that can lead to significant functional impairments and substantially disrupt the quality of life for patients. However, there has been a limited breakthrough in achieving neuralized and vascularized rapid bone regeneration. In this study, we collaborated with recombinant humanized collagen 1 (rhCOL1), native bone composite inorganic salts (NBCISs), methacrylated silk fibroin (SilMA), and bone marrow mesenchymal stem cells (BMSCs) to construct biomimetic organic and bio-mineralized multifunctional organoids for the repair of bone defects, achieving neuralized and vascularized bone regeneration within just six weeks in rabbits. We first determined the optimal concentration of SilMA (10%) by comprehensively evaluating crosslinking, operability, and BMSC proliferation. The rhCOL1 and NBCIS mixture was prepared using a ratio of 3:7, in reference to native bone, and was subsequently added to create biomimetic organic and biomineralized microenvironments for the NCSilMA. Similarly, the proportions of the added mixture were optimized based on their effects on compressive modulus, swelling, and degradation. As a result, we successfully constructed a biomimetic organic and biomineralized multifunctional hydrogel scaffold for bone defect repair, characterized by excellent biodegradability, appropriate strength, good biocompatibility, and osteoinductive biological function. Finally, the BMSC-loaded NCSilMA (organoids) achieved neuralized and vascularized rapid bone regeneration, with up-regulated osteogenic genes and enhanced cell colonization, collagen, and polysaccharide deposition.