Glycosaminoglycan-Mimetic Sulfated Chitosan Promotes Extracellular Matrix Formation and Regulates Inflammation to Alleviate Osteoarthritis.

Osteoarthritis (OA) is a multifactorial degenerative joint disease characterized by chronic inflammation, progressive cartilage extracellular matrix (ECM) degradation, and impaired joint lubrication, creating a complex pathological microenvironment that remains challenging to treat. In this study, a glycosaminoglycan (GAG)-mimetic sulfated chitosan (SCS) was synthesized via chemical modification of chitosan by grafting sulfonic acid groups, aiming to address these pathological features simultaneously. The therapeutic potential of SCS in OA was systematically evaluated. In vitro results demonstrated that SCS significantly promoted ECM synthesis in chondrocytes. Tribological analysis further revealed that SCS effectively enhanced cartilage lubrication in OA porcine cartilage, as evidenced by a marked reduction in the coefficient of friction, which decreased by 19% under a 5 N load and by 30% under a 10 N load. PCR analysis showed that SCS treatment significantly upregulated chondrogenic-related genes. In addition, SCS exhibited pronounced anti-inflammatory effects by downregulating the expression of inflammatory and catabolic genes. Importantly, in vivo studies demonstrated that SCS effectively preserved cartilage ECM and alleviated synovitis. Collectively, these findings indicate that SCS can simultaneously promote cartilage matrix regeneration, improve lubrication, and suppress inflammation, thereby effectively alleviating OA progression in a complex pathological environment. This study highlights the potential of SCS as a multifunctional GAG-mimetic biomaterial for osteoarthritis therapy.