Facile synthesis of in situ bismuth-doped calcium phosphate nanocomposite integrated injectable biopolymer hydrogel slurry for bone regeneration

The bionics of natural bone structures plays an essential role in the selection of materials for bone tissue engineering. Although the content of trace metallic elements in bone is low, they have significant effects on the process of bone growth and metabolism. Up to now, the applications of "green" heavy metals in bone regeneration are limited. Herein, in this study, we present a straightforward one-pot strategy for the synthesis of in situ bismuth-doped amorphous calcium phosphate nanocomposites (RBCP), effectively integrating the beneficial properties of each component. The characterization of these products can be readily optimized by adjusting reaction parameters. Our in vitro studies show that under coordination of each component, the RBCP biomaterial demonstrates distinguished biocompatibility and significantly accelerates vascular pattern formation within just 4 h by stimulating the expression of angiogenesis-related genes in human umbilical vein endothelial cells (HUVECs). In vivo experiments indicate that the incorporation of bismuth effectively enhances bone regeneration and osseointegration in a rat femur defect model. In conclusion, the as-prepared RBCP biomaterials hold promising prospects for treating segmental bone defects, owing to the facile, cost-effective, and eco-friendly preparation process, along with their remarkable capabilities.