Bioactive hydrogels for bone tissue engineering: Design strategies, bioactive cargo delivery, and artificial intelligence-assisted clinical translation.

The functional reconstruction of bone defects caused by trauma, infection, surgical resection and degenerative diseases poses substantial clinical challenges. Bone tissue engineering (BTE) holds immense potential for treating bone defects while avoiding complications commonly associated with conventional autografts, allografts and internal fixation. Bioactive hydrogels with exceptional drug delivery capabilities, excellent biocompatibility and tunable physicochemical properties have emerged as promising biomaterial scaffolds for BTE. This review provides a comprehensive overview of recent advancements in bioactive hydrogel-based strategies for BTE applications. An initial introduction to bone physiology is followed by a critical discussion of the design considerations for hydrogel platforms, specifically biomaterial selection, innovative crosslinking mechanisms and bioactive functionalization. Furthermore, hydrogel engineering for the controlled delivery of bioactive cargo is critically examined, with an emphasis on spatiotemporally programmable release behaviors that coordinate osteogenesis, angiogenesis and immunomodulation. Finally, key translational challenges are discussed, and the emerging role of artificial intelligence-assisted design is explored as a transformative approach for facilitating the clinical translation of next-generation bioactive hydrogels for BTE.