Bioinspired nanozyme-reinforced hydrogels with free radical scavenging capability for treating temporomandibular joint osteoarthritis

Temporomandibular joint osteoarthritis (TMJ-OA) is usually caused by increased friction at the joint interface, excessive release of inflammatory factors and catabolic enzymes, and free radical accumulation, which can lead to accelerated degradation and damage of cartilage. In this study, we develop a biological metabolism-inspired injectable hydrogel crosslinking by hydrazide modified hyaluronic acid (HA-HYD), aldehyde modified hyaluronic acid (HA-ALD), and ε-polylysine coated catalase-mimic nanozyme (mesoporous manganese cobalt oxide). Herein, this nanozyme-reinforced hydrogel with outstanding and durable reactive oxygen species (ROS) depletion capability and biocompatibility can alleviate the oxidative stress microenvironment, improve cell viability and proliferation, as well as up-regulate chondrogenic related gene expression and cartilage matrix formation of chondrocytes in vitro. Intra-articular administration of this engineered hydrogel can effectively scavenge endogenous over-expressed ROS to ameliorate the harsh microenvironment in the cavity of TMJ-OA. The nanozyme-reinforced hydrogel reduced proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and enhance anti-inflammatory cytokines (IL-10) expression, induced polarization of synovial macrophages towards M2 phenotype, alleviated structural damage to the cartilage and subchondral bone of the condyle, thus reducing cartilage matrix destruction and protect cartilage in osteoarthritis. In summary, the bioinspired nanozyme-reinforced hydrogels might be used as a promising ROS scavenger for treatment of TMJ-OA.