Hydration‐Lubricated, Cartilage‐Targeted, and Anti‐Inflammatory Triple‐Functional Nanospheres for the Treatment of Osteoarthritis

Abstract Osteoarthritis (OA) is a chronic joint disease characterized by increased mechanical friction, synovial inflammation, and irreversible pathological transformation caused by the progressive degeneration and wear of articular cartilage. Therefore, enhancing lubrication and suppressing inflammation, specifically at sites of cartilage damage, represents an effective approach for the treatment of OA. This study develops triple‐functional nanospheres (bMSNs@MPC‐HBA) by modifying the surface of biodegradable mesoporous silica nanoparticles (bMSNs) with the zwitterionic polymer poly (2‐methacryloyloxyethyl phosphorylcholine) and aldehyde groups, inspired by the hydration lubrication mechanism of healthy articular cartilage and the exposure of amino groups linked to cartilage degeneration. Physicochemical characterization, in vitro tribological and cellular experiments, and in vivo animal studies show that, after pre‐encapsulation of an anti‐inflammatory drug, the nanospheres exhibited enhanced lubrication, cartilage‐targeted drug delivery, and anti‐inflammatory effects. These properties contribute to the protection of damaged articular cartilage, regulation of the joint microenvironment, and improve therapeutic outcomes in a model of OA. In addition, the nanospheres show good biocompatibility and markedly reduced macrophage uptake following intra‐articular injection. These multifunctional nanospheres, which show enhanced lubrication and sustained drug release, represent a promising biomaterial for targeted treatment of OA.