A Metal–Polyphenol Complex Eliminates Chondrocytic ROS to Ameliorate Osteoarthritis

Objective: Osteoarthritis (OA) is a degenerative joint disease characterized by progressive cartilage degradation and chronic inflammation. Currently, none of the available treatments can effectively halt or reverse the irreversible loss of extracellular matrix. In this study, we developed a hyaluronic acid (HA)-modified metal-phenolic network (MPN) nanostructure (FPB-HA) to enable targeted antioxidant delivery and microenvironmental regulation for OA therapy. Design: The coordinated chelating effect between Prussian blue nanoparticles (PBNPs) and ferulic acid (FA) was utilized to construct the MPN framework, followed by surface modification with HA. The biocompatibility, ROS-scavenging capacity, and anti-inflammatory effects of FPB-HA were evaluated in ATDC5 chondrocytes. The therapeutic efficacy was further assessed in an anterior cruciate ligament transection (ACLT)-induced OA mouse model through histological analysis and OARSI scoring. Results: FPB-HA exhibited excellent biocompatibility and potent ROS-scavenging activity in vitro. Western blot analysis demonstrated that FPB-HA significantly upregulated anabolic markers (SOX9, COL2, ACAN) while suppressing catabolic proteases (MMP13, ADAMTS4, ADAMTS5). In vivo, FPB-HA treatment markedly attenuated cartilage degeneration, reduced proteoglycan loss, and improved OARSI scores compared to the untreated OA group. Conclusions: The MPN-based FPB-HA nanocomposite effectively alleviates oxidative stress, suppresses catabolic signaling, and reinstates anabolic matrix synthesis in chondrocytes, providing a promising disease-modifying therapeutic strategy for early-stage OA.