The amelioration of cartilage degeneration by photo-crosslinked GelHA hydrogel and crizotinib encapsulated chitosan microspheres
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Pengfei Chen1,2,*, Sheng Mei1,2,*, Chen Xia1,2, Ren Zhu3, Yichuan Pang4, Jiying Wang1,2, Jianfeng Zhang1,2, Fangchun Shao5 and Shunwu Fan1,2
1Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China
2Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, 310016, China
3Department of Orthopaedics, Yiwu Chowzhou Hospital, Yiwu, 322000, China
4MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310016, China
5Department of Pulmonary, Zhejiang Provincial People’s Hospital, Hangzhou, 310016, China
*These authors have contributed equally to this work
Shunwu Fan, email: email@example.com
Keywords: osteoarthritis, hydrogel, angiogenesis
Received: October 09, 2016 Accepted: January 30, 2017 Published: February 27, 2017
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.
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