Nanozyme‐Engineered Hyaluronic Acid Adhesives Loading Platelet‐Rich Plasma for Multilayered Osteoarthritis Treatment with Pain‐Relief Effect

Abstract Osteoarthritis (OA) is the most common degenerative joint disease, causing pain, disability, and economic strain. Combining nanozymes with dopamine (DOPA)‐based adhesives offers a promising approach to effectively modulate the microenvironment of OA‐affected tissues. However, traditional fabrication methods of DOPA‐based adhesives often involve external oxidants or curing agents, which can introduce additional oxidative stress, posing systemic risks. Here, the different enzyme‐catalyzed activities of platinum–copper (PtCu) nanozymes at different pH values are utilized to directly catalyze the cross‐linking of DOPA‐modified hyaluronic acid (HAD), representing a new polymerization method for phenol‐based bioadhesives. The resulting adhesive (HAD/PtCu/platelet‐rich plasma (PRP)), when combined with PRP, effectively mitigates the generation of proinflammatory factors, scavenges reactive oxygen species, boosts the hypoxic chemotaxis of chondrocytes, stimulates chondrocyte proliferation and migration, and protects interleukin‐1β‐treated human articular chondrocyte C28/I2 cells from further OA advancement. Additionally, in vivo assessments show that HAD/PtCu/PRP significantly alleviates pain and improves the knee microenvironment in osteoarthritic rats. These findings suggest that HAD/PtCu/PRP provides a promising alternative in OA therapy.