Osteoarthritis (OA), a prevalent degenerative joint disorder characterized by articular cartilage deterioration, represents a major global health challenge. Recent studies highlight the pivotal role of reactive oxygen species (ROS)-mediated ferroptosis in OA pathogenesis. Here, we report a microenvironment-adaptive hydrogel system based on 2D vanadium nitride (V2N) MXene nanoenzyme (hereafter denoted as V2N MXenzyme@Gel). This system features a dual-crosslinked network that optimally balances between mechanical robustness and flexibility. Crucially, the V2N MXenzyme establishes a self-sustaining "capture-conversion-recycling" catalytic cycle, mimicking both superoxide dismutase (SOD) and catalase (CAT) activities. The cycle not only neutralizes detrimental ROS into water (H2O) and oxygen (O2) but also generates nitric oxide (NO), collectively alleviating oxidative damage. Mechanistically, V2N MXenzyme@Gel effectively scavenges ROS, attenuates oxidative stress, and suppresses ferroptosis by regulating the Hspa5/GPX4 axis, while concurrently restoring the metabolic homeostasis of chondrocyte extracellular matrix (ECM). Meanwhile, intra-articular administration of V2N MXenzyme@Gel significantly attenuates cartilage degradation and inflammation levels in OA rats. Collectively, our work presents a V2N MXenzyme@Gel with dual capabilities for ROS elimination and ferroptosis blockade, demonstrating its efficacy in arresting OA progression and proposing a novel precision strategy for managing chronic joint diseases.
Li et al. (Sat,) studied this question.