Mn3O4@PDA nanozyme with high-efficiency enzyme-like activity and good biocompatibility reduce oxidative stress and inflammation to alleviate osteoarthritis

Reactive oxygen species (ROS) are closely associated with the initiation and progression of osteoarthritis (OA). Scavenging ROS within inflamed chondrocytes represents an effective strategy to treat OA. In this study, mimicking natural Mn-SOD, we successfully constructed a nanozyme with Mn 3 O 4 as the core and polydopamine (PDA) as the outer modification. Density Functional Theory (DFT) calculations combined with Electron Spin Resonance (ESR) detection revealed that the nanozyme demonstrates high enzyme-like activity. Furthermore, cytotoxicity assays confirmed its excellent biocompatibility. Within inflamed chondrocytes, Mn 3 O 4 @PDA nanozyme had been demonstrated to regulate the oxidative stress microenvironment, thereby inhibiting inflammatory responses. Moreover, injecting Mn 3 O 4 @PDA into the joints of rats with osteoarthritis could effectively alleviate the inflammatory response and relieve the degeneration of articular cartilage, reducing the OARSCI score by 85.25% at 8 weeks. Therefore, this study demonstrated that Mn 3 O 4 @PDA with high enzyme-like activity and good biocompatibility could efficiently scavenge ROS, reduce inflammatory responses, and promote cartilage regeneration, thereby achieving the treatment of OA.