Ruthenium Oxide Nanozyme for Tendinopathy Treatment via Countering Ferroptosis

Abstract The global prevalence of tendinopathy (TP) is steadily increasing, resulting in functional impairments in tendons across individuals of all ages. Excessive accumulation of reactive oxygen species (ROS) plays a pivotal role in the development of TP, which compromises tendon repair and integrity through oxidative stress. This process is often accompanied by ferroptosis—a newly recognized form of iron‐dependent programmed cell death. This study explores ruthenium oxide (RuO 2 ) hollow nanospheres as an effective nanozyme to address oxidative damage and ferroptosis in type I collagenase‐induced TP. In vitro experiments show decreased mRNA levels of inflammatory biomarkers in tenocytes, while western blot analysis and immunofluorescence reveal reduced extracellular matrix degradation after RuO 2 treatment. In the TP model, the RuO 2 nanozyme therapy and improves tendon fiber arrangement, alleviates pain, and increases type I collagen expression while preventing matrix degradation. These findings suggest that the RuO 2 nanozyme possesses significant antioxidant and anti‐inflammatory properties, providing protective effects on tenocytes by ROS scavenging and countering ferroptosis, indicating its potential for treating TP.