Osteomimix: A Multidimensional Biomimetic Cascade Strategy for Bone Defect Repair

Despite advancements in biomimetic mineralization techniques, the repair of large-scale bone defects remains a significant challenge. Inspired by the bone formation process, a multidimensional biomimetic cascade strategy is developed by replicating the biomineralization cascade, emulating the hierarchical structure of bone, and biomimicking its biological functions for efficient bone regeneration. This strategy involves the photocrosslinking of sodium methacrylate carboxymethyl cellulose-stabilized amorphous magnesium-calcium phosphate with methacrylate-modified type I collagen to create a self-mineralizing hydrogel. The hydrogel is then integrated with either naturally derived or synthetic oriented bulk scaffolds. The resulting composite, named Osteomimix, provides excellent mechanical support and can be customized for irregular bone defects using CAD/CAM technology. Through in vitro and in vivo studies, this work finds that Osteomimix exhibits spontaneous in situ biomimetic mineralization in a cell-free environment, while modulating immune responses and promoting vascularized bone formation in a cell-dependent manner. Built on bone-specific insights, this strategy achieves biomimicry across temporal, spatial, and functional dimensions, facilitating the seamless integration of artificial constructs with the natural tissue repair dynamics.