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

Chen Xia; Pengfei Chen; Sheng Mei; Lei Ning; Chenyang Lei; Jiying Wang; Jianfeng Zhang; Jianjun Ma; Shunwu Fan

doi:10.18632/oncotarget.13748

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Research Papers:

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

Chen Xia, Pengfei Chen, Sheng Mei, Lei Ning, Chenyang Lei, Jiying Wang, Jianfeng Zhang, Jianjun Ma and Shunwu Fan _

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Oncotarget. 2017; 8:2835-2849. https://doi.org/10.18632/oncotarget.13748

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Abstract

Chen Xia1,2,*, Pengfei Chen1,2,*, Sheng Mei1,2, Lei Ning1,2, Chenyang Lei1,2, Jiying Wang1,2, Jianfeng Zhang1,2, Jianjun Ma1,2, Shunwu Fan1,2

1Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China

2Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China

*These authors contributed equally to this work

Correspondence to:

Shunwu Fan, email: [email protected]

Jianjun Ma, email: [email protected]

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.

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Research Papers:

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

Abstract