Molten-Salt-Mediated Synthesis of Atomic Manganese/Cobalt Catalysts on Bioceramic Microparticles for Catalytic Anti-Osteoarthritis Treatments.

Osteoarthritis (OA) is a chronic progressive joint disease characterized by cartilage degeneration and local inflammation, and its progression is closely related to the excessive production of reactive oxygen species (ROS). Despite progress made with small molecule antioxidants and nanozymes, effective antioxidant therapy for the long-term elimination of these ROS remains challenging, largely due to the rapid clearance of antioxidants from the joints via synovial vessels and lymphatics. Herein, a molten-salt method is developed to facilitate the atomic dispersion of Mn or Co ions homogeneously on the surface of akermanite microparticles (AKT-MPs). The micrometer-scale Mn- or Co-AKT-MPs with multi-mimetic enzyme effects are demonstrated to obliterate multiple ROS, thereby protecting the inherent homeostasis between chondrocyte anabolism and catabolism, while suppressing the conversion of macrophages to a pro-inflammatory phenotype. In addition, the microparticles exhibited chondroprotection of ROS-challenged cartilage explants in vitro by limiting the loss of cartilage extracellular matrix (ECM) and the release of degradative enzymes. Furthermore, Mn- or Co-AKT-MPs are injected intra-articularly into monosodium iodoacetate (MIA)-induced OA mice and effectively suppress synovial inflammation, painful symptoms, and progression of early cartilage destruction. Therefore, this microparticle-based antioxidant therapy provides an insight and paradigm to control atomic catalysts integrated with microparticles for efficient catalytic anti-OA treatments.