The amelioration of cartilage degeneration by photo-crosslinked GelHA hydrogel and crizotinib encapsulated chitosan microspheres

// Pengfei Chen 1, 2, * , Sheng Mei 1, 2, * , Chen Xia 1, 2 , Ren Zhu 3 , Yichuan Pang 4 , Jiying Wang 1, 2 , Jianfeng Zhang 1, 2 , Fangchun Shao 5 and Shunwu Fan 1, 2 1 Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China 2 Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, 310016, China 3 Department of Orthopaedics, Yiwu Chowzhou Hospital, Yiwu, 322000, China 4 MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310016, China 5 Department of Pulmonary, Zhejiang Provincial People’s Hospital, Hangzhou, 310016, China * These authors have contributed equally to this work Correspondence to: Shunwu Fan, email: shunwu_fan@126.com Keywords: osteoarthritis, hydrogel, angiogenesis Received: October 09, 2016     Accepted: January 30, 2017     Published: February 27, 2017 ABSTRACT The present study aimed to investigate the synergistic therapeutic effect of decreasing cartilage angiogenesis via exposure to crizotinib encapsulated by chitosan microspheres and photo-crosslinked hydrogel, with the goal of evaluating crizotinib as a treatment for osteoarthritis. First, we developed and evaluated the characteristics of hydrogels and chitosan microspheres. Next, we measured the effect of crizotinib on the cartilage degeneration induced by interleukin-1β in chondrocytes. Crizotinib ameliorated the pathological changes induced by interleukin-1β via its anti-angiogenesis function. In addition, we surgically induced osteoarthritis in mice, which were then injected intra-articularly with crizotinib-loaded biomaterials. Cartilage matrix degradation, expression of vascular endothelial growth factor and extracellular signal-regulated kinases 1/2 were evaluated after surgery. Treatment with the combination of crizotinib-loaded biomaterials retarded the progression of surgically induced osteoarthritis. Crizotinib ameliorated cartilage matrix degradation by promoting anti-angiogenesis and impeding extracellular signal-regulated kinases 1/2 signaling pathway. Our results demonstrate that the combination of photo-crosslinked hydrogel and crizotinib-loaded chitosan microspheres might represent a promising strategy for osteoarthritis treatment.