Photocrosslinkable hydrogel of kartogenin functionalized chitosan methacrylate preserves chondrogenesis

Cartilage damage- and degeneration-related osteoarthritis (OA) causes inconvenience and pain to patients. Hydrogels loaded with therapeutics are receiving increasing attention. Kartogenin (KGN), a small molecule drug, has been proven to be effective in protecting cartilage regeneration. However, its non-water-soluble nature poses a limitation to its application. Herein, we report a feasible and facile approach to graft KGN to chitosan (CS) and then modify the obtained CS-KGN conjugate with methacrylic anhydride (MA) to prepare photocrosslinkable CS-KGN methacrylate (CS-KGN-MA) hydrogels with injectability and in situ gel formation for cartilage repair. The CS-KGN conjugate showed improved water-soluble properties for subsequent chemical modification to synthesize CS-KGN-MA. In the presence of photoinitiator, the CS-KGN-MA solution could form stable hydrogels under visible light (405 nm) irradiation. Notably, upon entry into the physiological environment, CS-KGN-MA allowed for sustained drug release as the amide bond was hydrolyzed. In vitro, the CS-KGN-MA system showed a high survival rate and maintained the chondrogenesis of chondrocytes. In situ, the CS-KGN-MA demonstrated a strong ability to repair cartilage defect. This work provides a promising drug-carrying hydrogel system for cartilage repair.