Injectable Chondroitin Sulfate Microspheres with Gallic Acid-Magnesium MOF for Anti-Inflammatory and Cartilage Degeneration Alleviation in Osteoarthritis Treatment
Jiachen He, Jianjun Wu, Jingcheng Zheng, Yidan Xu, King Ho Holden Li, Siwei Yin, Yanyun Liu, Yuelin Hu, Chaoming Xie, Limin Cai, Yi Du, Xiong Lu
Abstract
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 Mg 2+ ions release from pGM, improving the inflammatory microenvironment of the articular cavity and mitigating oxidative stress. The sustained release of Mg 2+ 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.