Thermosensitive injectable hydrogel loaded with hypoxia-induced exosomes maintains chondrocyte phenotype through NDRG3-mediated hypoxic response |
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| Institution: | 1. Medical College, Guizhou University, Guiyang 550000, China;2. Department of Orthopedics, Guizhou Provincial People''s Hospital, Guiyang 550000, China;3. Department of Orthopaedics, The Affiliated Hospital of Guizhou Medical University, Guiyang 550000, China;1. CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China;2. University of Chinese Academy of Sciences, Beijing 100049, China;3. Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian 116024, China;1. State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China;2. Economical Forest Cultivation and Utilization of 2011 Collaborative Innovation Center in Hunan Province, Hunan Key Laboratory of Green Chemistry and Application of Biological Nanotechnology, Hunan University of Technology, Zhuzhou 412007, China;1. Department of Orthopedics, Guizhou Provincial People''s Hospital, Guiyang 550000, China;2. Medical College, Guizhou University, Guiyang 550000, China;3. Department of Materials Science and Engineering, Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD 21218, United States;4. Department of Endocrinology and Metabolism, Guizhou Provincial People''s Hospital, Guiyang 550000, China;5. The Central Laboratory, Guizhou Provincial People''s Hospital, Guiyang 550000, China;6. Department of Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang 550000, China;1. CAS Key Laboratory of Environmental and Applied Microbiology, Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China;2. College of Resources and Environmental Engineering, Mianyang Normal University, Mianyang 621000, China;3. Department of Materials and Chemical Engineering, Yibin University, Yibin 644000, China;1. PCFM, LIFM Lab, School of Chemistry, Sun Yat-sen University, Guangzhou 510275, China;2. Guangdong Provincial Key Laboratory of Optical Chemicals, Xinhuayue Group, Maoming 525000, China;3. Shenzhen Grubbs Institute, Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China;4. Pohang Accelerator Laboratory, Postech, Pohang, Gyeongbuk, Korea |
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| Abstract: | Current clinical treatments cannot effectively delay the progression of osteoarthritis (OA). Consequently, joint replacement surgery is required for late-stage OA when patients cannot tolerate pain and joint dysfunction. Therefore, the prevention of OA progression in the early and middle stages is an urgent clinical problem. In a previous study, we demonstrated that NDRG3-mediated hypoxic response might be closely related to the development and progression of OA. In this study, an injectable thermosensitive hydrogel was established by cross-linking Pluronic F-127 and hyaluronic acid (HA) for the sustained release of hypoxia-induced exosomes (HExos) derived from adipose-derived mesenchymal stem cells. We demonstrated that for OA at the early and middle stages, the HExos-loaded HP hydrogel could maintain the chondrocyte phenotype by enhancing chondrocyte autophagy, reducing chondrocyte apoptosis, and promoting chondrocyte activity and proliferation through the NDRG3-mediated hypoxic response. This novel composite hydrogel, which could activate the NDRG3-mediated hypoxic response, may provide new ideas and a theoretical basis for the treatment of early- and mid-stage OA. |
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