Dual-Modular Hydrogel Microparticles with Precision-Modulation of Inflammatory Microenvironment Dictate Full-Thickness Cartilage Regeneration for Osteoarthritis Repair

Osteoarthritis (OA) is a typical degenerative disease characterized primarily by the degeneration of cartilage. However, current treatments for cartilage degeneration often lead to the formation of hypertrophic cartilage and fibrocartilage, making it challenging to achieve full-thickness cartilage. Here, dual-modular hydrogel microparticles (dmHMPs) are developed, which enable precise spatio-temporal modulation and dynamic equilibrium between immune responses and cartilage regeneration. dmHMPs can modulate the inflammatory microenvironment of the joint by promoting the polarization of synovial macrophages toward an anti-inflammatory phenotype. Consequently, as inflammation is mitigated, synovium-derived mesenchymal stem cells recruited by dmHMPs can efficiently undergo chondrogenic differentiation to repair damaged cartilage in situ. In vivo experiments demonstrate that dmHMPs significantly suppress the expression of Indian hedgehog (Ihh) and collagen type X, thereby reducing the formation of hypertrophic cartilage and preserving the structural integrity and biological functions of articular cartilage. This therapeutic modulates the dynamic balance between inflammation and repair, providing a promising approach for full-thickness cartilage regeneration.