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Engineered MgO nanoparticles for cartilage-bone synergistic therapy
Liming Zheng1,2,3,4, Sheng Zhao2, Yixuan Li1
1Division of Sports Medicine and Adult Reconstructive Surgery, Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University; Branch of National Clinical Research Center for Orthopedics, Sports Medicine and Rehabilitation; Institute of Medical 3D Printing, Nanjing University; Jiangsu Engineering Research Center for 3D Bioprinting, Nanjing 210008, Jiangsu, PR China.
Abstract:
The emerging therapeutic strategies for osteoarthritis (OA) are shifting toward comprehensive approaches that target periarticular tissues, involving both cartilage and subchondral bone. This shift drives the development of single-component therapeutics capable of acting on multiple tissues and cells. Magnesium, an element essential for maintaining skeletal health, shows promise in treating OA. However, the precise effects of magnesium on cartilage and subchondral bone are not yet clear. Here, we investigated the therapeutic effect of Mg2+ on OA, unveiling its protective effects on both cartilage and bone at the cellular and animal levels. The beneficial effect on the cartilage-bone interaction is primarily mediated by the PI3K/AKT pathway. In addition, we developed poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with nano-magnesium oxide modified with stearic acid (SA), MgO&SA@PLGA, for intra-articular injection. These microspheres demonstrated remarkable efficacy in alleviating OA in rat models, highlighting their translational potential in clinical applications.
