Injectable Bioactive Antioxidative One‐Component Polycitrate Hydrogel with Anti‐Inflammatory Effects for Osteoarthritis Alleviation and Cartilage Protection

Abstract Chronic inflammation in osteoarthritis (OA) can destroy the cartilage extracellular matrix (ECM), causing cartilage damage and further exacerbating the inflammation. Effective regulation of the inflammatory microenvironment has important clinical significance for OA alleviation and cartilage protection. Polycitrate‐based polymers have good antioxidant and anti‐inflammatory abilities but cannot self‐polymerize to form hydrogels. Herein, a one‐component multifunctional polycitrate‐based (PCCGA) hydrogel for OA alleviation and cartilage protection is reported. The PCCGA hydrogel is prepared using only the PCCGA polymer by self‐polymerization and exhibits multifunctional properties such as injectability, adhesion, controllable pore size and elasticity, self‐healing ability, and photoluminescence. Moreover, the PCCGA hydrogel exhibits good biocompatibility, biodegradability, antioxidation by scavenging intracellular reactive oxygen species, and anti‐inflammatory ability by downregulating the expression of proinflammatory cytokines and promoting the proliferation and migration of stem cells. In vivo results from an OA rat model show that the PCCGA hydrogel can effectively alleviate OA and protect the cartilage by restoring uniform articular surface and cartilage ECM levels, as well as inhibiting cartilage resorption and matrix metalloproteinase‐13 levels. These results indicate that the PCCGA hydrogel, as a novel bioactive material, is an effective strategy for OA treatment and has broad application prospects in inflammation‐related biomedicine.