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

Beijie Qi; Zhixin Chen; Han Lin; Yaying Sun; Chengqing Yi; Jiwu Chen

doi:10.1016/j.mtbio.2025.101979

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

Mater Today Bio. 2025 Jun 11:33:101979. doi: 10.1016/j.mtbio.2025.101979. eCollection 2025 Aug.

Authors

Beijie Qi¹, Zhixin Chen², Han Lin^{2

3}, Yaying Sun⁴, Chengqing Yi¹, Jiwu Chen⁴

Affiliations

¹ Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, Shanghai, 201399, China.
² Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, China.
³ Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, Shanghai, 200050, China.
⁴ Department of Sports Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China.

Abstract

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.

Keywords: Adhesive capsulitis of shoulder; Fibrosis; Nanosheet; Reactive oxygen species; p38 MAPK.