Pathology-guided design of injectable hydrogels for precision therapy and cartilage regeneration in osteoarthritis

Osteoarthritis (OA) is a highly prevalent degenerative joint disease whose complex pathological microenvironment and limited cartilage self-repair capacity have resulted in the absence of therapeutic approaches capable of simultaneously achieving structural reconstruction and functional recovery. Current clinical strategies face significant limitations, as conventional pharmacological treatments can only alleviate symptoms with accompanying systemic side effects, while surgical interventions often encounter challenges such as inadequate mechanical properties of repaired tissues and long-term degeneration. The precise functionalization of injectable hydrogels represents a key strategy for cartilage regeneration and the core challenge lies in integrating multiple material properties to design on-demand delivery platforms that can dynamically respond to complex pathological microenvironments in vivo. This review systematically elaborates on precision customization strategies for injectable hydrogels based on OA pathological mechanisms, focusing on how hydrogel design responds to pathological signals in the joint microenvironment to achieve on-demand and precise regulation of therapeutic agents including drugs, cells and genes. Beginning with cartilage structure and injury mechanisms, this article analyzes the limitations of existing pharmacological and surgical repair methods, then, elaborate on the multifunctional platform role of hydrogels in cartilage tissue engineering, including recent advances in mechanical design, drug loading/release behavior, inflammation regulation, stem cell delivery and gene-activated repair. Finally, it outlines challenges and future directions for smart hydrogels in cartilage regenerative medicine, aiming to provide a theoretical framework and technical pathway for integrating materials science with clinical medicine.