Mingming Zhao, Xiaonong Zhang, Chunsheng Xiao, Xuesi Chen
Bone mineralization is a tightly regulated process involving the deposition of hydroxyapatite and other calcium salt crystals within the collagen-rich extracellular matrix of bone tissue, which confers hierarchical architecture and exceptional biomechanical properties to bone through this organized biocrystal arrangement. Inspired by this natural process, biomimetic mineralized hydrogels, engineered to mimic the chemical composition, structural organization, mechanical strength, and osteoinductive capabilities of bone tissue, have garnered considerable attention as promising candidates for bone regeneration. This review systematically summarizes recent progress in the design and application of biomimetic mineralized hydrogels for bone regeneration. Following an overview of natural biomineralization principles, innovative strategies for constructing heterogeneous and homogeneous biomimetic mineralized hydrogels are first highlighted, emphasizing their structural and functional mimicry. Subsequently, their therapeutic applications are critically examined, including bone defect repair, osteochondral regeneration, osteoporotic bone repair, and other bone-related diseases (e.g., osteosarcoma, tendon-bone interface injury). Finally, persistent challenges are identified, and future research directions are proposed to advance these hydrogel systems toward clinical translation in bone tissue engineering.