Antioxidant RuCo nanosheet attenuates capsule fibrosis in adhesive capsulitis of shoulder by p38 MAPK signaling pathway inhibition

Adhesive capsulitis of shoulder (ACS) is a prevalent orthopedic disorder characterized by pain and restricted range of motion (ROM). The pathogenesis of ACS remains unclear and current treatments have limited efficacy in terms of long-term outcomes. Here, we synthesized antioxidant RuCo nanosheets (RuCo-NSs) for the treatment of ACS. The reactive oxygen species (ROS) scavenging ability and the effect of RuCo-NSs on the activation of mouse fibroblasts NIH3T3s were investigated. In addition, RuCo-NSs were administered to the mouse model of ACS through intra-articular injection into joint capsule. Results showed that RuCo-NSs could effectively scavenge ROS in both the acellular and intracellular environments with low toxicity. Moreover, RuCo-NSs significantly suppressed the proliferation, migration and fibrogenesis of NIH3T3 via modulating the p38 mitogen-activated protein kinase (MAPK) signaling pathway. In addition, RuCo-NSs improved shoulder stiffness and inhibited capsular fibrosis in ACS mice. Our results suggest that the use of RuCo-NSs may be a potential therapy for ACS.