Injectable Chondroitin Sulfate Microspheres with Gallic Acid-Magnesium MOF for Anti-Inflammatory and Cartilage Degeneration Alleviation in Osteoarthritis Treatment

Inflammation and cartilage degeneration are critical challenges in osteoarthritis (OA) treatment. Achieving sustained drug efficacy while mitigating the adverse effects of inflammation and reactive oxygen species remains a significant challenge. This study synthesizes a gallic acid-magnesium (GA-Mg) metal–organic framework (MOF) as a drug carrier for puerarin (PA). The PA-loaded GA-Mg MOF (pGM) is encapsulated within chondroitin sulfate methacrylate, forming monodisperse hybrid microspheres (CM@pGM) under ultraviolet light using microfluidic technology. The pGM is physically confined within the microspheres through a network of structural obstructions and noncovalent interactions. During degradation, GA and Mg2+ ions release from pGM, improving the inflammatory microenvironment of the articular cavity and mitigating oxidative stress. The sustained release of Mg2+ and PA supports chondrocyte anabolism and facilitates cartilage repair. In vitro studies confirm that injectable microspheres extend the drug release period to over 2 weeks. In vivo experiments demonstrate that CM@pGM significantly reduces osteophyte formation, alleviates degenerative changes in articular cartilage, and delays OA progression. In conclusion, CM@pGM, as a drug delivery platform that ameliorates the inflammatory microenvironment, alleviates oxidative stress, and promotes cartilage repair, holds significant potential for OA treatment.