Lubricating MXenzyme-based hybrid hydrogel reverses oxidative damage to alleviate osteoarthritis

Osteoarthritis (OA) is a lubrication-deficient joint disease accompanied by persistent inflammation and progressive destruction of articular cartilage. Although the exact pathogenesis is still unclear, oxidative stress-induced metabolic imbalance and chondrocyte death are thought to take on a crucial role. Here, we present an injectable hydrogel drug delivery system based on V2C MXenzyme NS, metformin and DexMA to alleviate the progression of OA. Due to the advantageous properties of MXenzyme, MXenzyme hybrid hydrogel not only enabled the intelligent release of metformin in response to pH, but also formed a lubricant layer on the hydrogel surface for stable boundary lubrication. Moreover, MXenzyme hybrid hydrogel could scavenge excess reactive oxygen species (ROS) in chondrocytes, including H2O2 and O2−, to alleviate oxidative stress and protect mitochondrial function. Most notably, MXenzyme Hybrid Hydrogel also maintained cartilage extracellular matrix metabolic homeostasis and inhibited chondrocyte pyroptosis through activating Nrf2-ARE signaling, thereby protected cartilage tissues and mitigated the progression of OA. Collectively, the MXenzyme hybrid hydrogel is a promising nano-delivery system for the treatment of OA.