Photo-crosslinked HAMA hydrogel with cordycepin encapsulated chitosan microspheres for osteoarthritis treatment

// Chen Xia 1, 2, * , Pengfei Chen 1, 2, * , Sheng Mei 1, 2 , Lei Ning 1, 2 , Chenyang Lei 1, 2 , Jiying Wang 1, 2 , Jianfeng Zhang 1, 2 , Jianjun Ma 1, 2 , Shunwu Fan 1, 2 1 Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China 2 Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China * These authors contributed equally to this work Correspondence to: Shunwu Fan, email: shunwu_fan@126.com Jianjun Ma, email: 21528678@zju.edu.cn Keywords: hydrogel, cordycepin, autophagy, osteoarthritis Received: July 28, 2016      Accepted: November 22, 2016      Published: December 01, 2016 ABSTRACT Autophagy is a protective mechanism in normal cartilage. The present study aimed to investigate the synergistic therapeutic effect of promotion of chondrocyte autophagy via exposure to cordycepin encapsulated by chitosan microspheres (CM-cordycepin) and photo-crosslinked hyaluronic acid methacrylate (HAMA) hydrogel, with the goal of evaluating CM-cordycepin as a treatment for patients with osteoarthritis. First, we developed and evaluated the characteristics of HAMA hydrogels and chitosan microspheres. Next, we measured the effect of cordycepin on cartilage matrix degradation induced by IL1-β in chondrocytes and an ex vivo model. Cordycepin protects cartilage from degradation partly by activation of autophagy. Moreover, we surgically induced osteoarthritis in mice, which were injected intra-articularly with CM-cordycepin and HAMA. The combination of CM-cordycepin and HAMA hydrogel retarded the progression of surgically induced OA. Cordycepin ameliorated cartilage matrix degradation at least partially by inducing autophagy in vivo . Our results demonstrate that the combination of cordycepin encapsulated by CMs and photo-crosslinked HAMA hydrogel could be a promising strategy for treating patients with osteoarthritis.