Fabrication of a novel carboxymethyl chitosan-manganese complex and its multidimensional regulatory effects on the joint microenvironment in early osteoarthritis.

The treatment of early-stage osteoarthritis (OA) remains clinically challenging, characterized by articular cartilage inflammation, cartilage damage and subchondral bone loss. Carboxymethyl chitosan-manganese (CMCMn), a novel therapeutic agent synthesized by integrating carboxymethyl chitosan (CMC) with manganese (Mn), was designed to ameliorate early OA through multi-modal regulation of the joint microenvironment. In vitro, investigations demonstrated that CMCMn effectively promoted chondrocyte anabolism by enhancing the synthesis of key extracellular matrix components while simultaneously attenuating catabolic processes mediated by inflammatory factors, thereby creating a conducive environment for cartilage repair. Furthermore, CMCMn exhibited potent immunomodulatory capabilities by suppressing the pro-inflammatory polarization of monocyte-derived macrophages and downregulating the secretion of inflammatory cytokines, which contributed to restoring immune homeostasis. In vivo assessments in a rodent OA model revealed that treatment with CMCMn led to significant preservation of articular cartilage integrity, a marked reduction in overall joint inflammation scores, and a notable mitigation of subchondral bone loss. These combined effects resulted in the effective deceleration of structural disease progression. Collectively, our findings highlight that CMCMn possesses integrated anti-inflammatory, chondroprotective, and bone-metabolism regulating properties. This multifaceted activity profile underscores its considerable potential as a promising and comprehensive therapeutic strategy for early-stage OA, offering a novel and promising avenue for future clinical translation.