title: Photo-crosslinked HAMA hydrogel with cordycepin encapsulated chitosan microspheres for osteoarthritis treatment.
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.
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.|Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xia
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.|Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.|Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Mei
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.|Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ning
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.|Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Chenyang
authors.initials: C
authors.lastname: Lei
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.|Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Jiying
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.|Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.|Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.|Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China.
authors.forename: Shunwu
authors.initials: S
authors.lastname: Fan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002358:Cartilage, Articular; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D019902:Chondrocytes / Q000187:drug effects; D003839:Deoxyadenosines / Q000008:administration & dosage* / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005455:Fluorescent Antibody Technique; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008863:Microspheres; D010003:Osteoarthritis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D006820:Hyaluronic Acid; D048271:Chitosan; C058120:cordycepin
keywords: autophagy; cordycepin; hydrogel; osteoarthritis