Dynamically Repairable Hydration-Lubricating Microspheres for Osteoarthritis Therapy

Osteoarthritis (OA) progression is closely associated with the deterioration of joint lubrication. Although surface-grafted lubrication coatings can reduce friction, they are susceptible to mechanical damage under repetitive shear stress, resulting in rapid lubrication failure. Therefore, constructing a dynamically reconfigurable lubrication interface capable of continuous restoration under friction is critical for long-term joint protection. Herein, a dynamically self-repairing hydration lubrication microsphere system (HMs-CD@Ad-PMPC) is developed based on host-guest interactions. β-Cyclodextrin (β-CD)-functionalized silk fibroin microspheres dynamically recruit adamantane (Ad)-terminated poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) brushes through supramolecular host-guest recognition, thereby establishing a robust yet reversible hydration lubrication interface. Under shear stress during joint motion, partial dissociation of Ad-PMPC chains induces transient lubrication attenuation, while spontaneous molecular reassembly rapidly restores the lubrication interface upon stress release, thereby enabling dynamic self-repairing lubrication. In vitro, HMs-CD@Ad-PMPC maintains a stable low coefficient of friction (COF, 0.03-0.04) under cyclic shear conditions, exhibiting excellent wear resistance and long-term lubrication stability. In vivo, the system effectively reduces joint wear, preserves cartilage integrity, and significantly delays OA progression. This work establishes a dynamic lubrication strategy capable of restoring interfacial functionality under mechanical stress, providing a promising platform for long-term joint lubrication and OA therapy.