Hydrogel Engineering Interventions for Precision Cartilage Regeneration: Bridging Pathological Mechanisms and Therapeutic Innovation

Although microfracture, osteochondral transplantation, and autologous chondrocyte implantation are commonly employed, accurately replicating the natural calcified layer at the cartilage-bone interface remains challenging, leading to structural and functional impairments in regenerated cartilage. For successful cartilage regeneration, engineered therapeutic materials must be tailored to the structural and pathophysiological characteristics of cartilage injury. This necessitates the development of strategic interventions based on a comprehensive understanding of the injured structure and microenvironment, including extracellular matrix degradation, inflammatory cascades, disrupted intercellular communication, and integrated pathophysiological networks. This review systematically elucidates microenvironment evolution and molecular mechanisms post-cartilage injury while highlighting the application of injectable hydrogels and 3D printing technology as delivery vehicles for various therapeutic agents (including drugs, cells, and genes) in tissue engineering. By emphasizing their unique capacity for designing customized systems to modulate the regeneration process, this work aims to establish a cohesive theoretical framework and a clear technical roadmap for guiding the future development of precise cartilage repair solutions.