Photo-crosslinked HAMA Hydrogel With Cordycepin Encapsulated Chitosa Microspheres Forosteoarthritis Treatment

Objective: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.Methods: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-? 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.Results:Our results demonstrate that firrst,cordycepin ameliorated cartilage degeneration in ex-vivo models;second,cordycepin enhanced autophagy in mouse chondrocytes and human OA cartilage;third,the combination of CM-cordycepin and HAMA hydrogel slowed the progression of degenerative changes in OA.Conclusions:The combination of CM-cordycepin and HAMA hydrogel retarded the progression of surgically induced OA.