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作 者:Zhicheng Cao Hongmei Wang Jialin Chen Yanan Zhang Qingyun Mo Po Zhang Mingyue Wang Haoyang Liu Xueyang Bao Yuzhi Sun Wei Zhang Qingqiang Yao
机构地区:[1]Department of Orthopaedic Surgery,Institute of Digital Medicine,Nanjing First Hospital,Nanjing Medical University,210006,Nanjing,China [2]School of Medicine,Southeast University,210009,Nanjing,China [3]Department of Pharmaceutical Sciences,Binzhou Medical University,264003,Yantai,Shandong,China [4]Jiangsu Key Laboratory for Biomaterials and Devices,Southeast University,210096,Nanjing,China [5]China Orthopedic Regenerative Medicine Group(CORMed),China
出 处:《Bioactive Materials》2023年第2期221-242,共22页生物活性材料(英文)
基 金:supported by the National Natural Science Foundation of China(81901903,5171101275,81771985,81972042,82072400);the Natural Science Foundation of Jiangsu Province(BK20190356,BK20190354,BK20200001,BE2019736,BE2019679);the Zhishan Scholars Programs of Southeast University and the Postgraduate Research and Innovation Project of Jiangsu Province(SJCX 21_0637).
摘 要:Osteochondral defects(OCD)cannot be efficiently repaired due to the unique physical architecture and the pathological microenvironment including enhanced oxidative stress and inflammation.Conventional strategies,such as the control of implant microstructure or the introduction of growth factors,have limited functions failing to manage these complex environments.Here we developed a multifunctional silk-based hydrogel incorporated with metal-organic framework nanozymes(CuTA@SF)to provide a suitable microenvironment for enhanced OCD regeneration.The incorporation of CuTA nanozymes endowed the SF hydrogel with a uniform microstructure and elevated hydrophilicity.In vitro cultivation of mesenchymal stem cells(MSCs)and chondrocytes showed that CuTA@SF hydrogel accelerated cell proliferation and enhanced cell viability,as well as had antioxidant and antibacterial properties.Under the inflammatory environment with the stimulation of IL-1β,CuTA@SF hydrogel still possessed the potential to promote MSC osteogenesis and deposition of cartilage-specific extracellular matrix(ECM).The proteomics analysis further confirmed that CuTA@SF hydrogel promoted cell proliferation and ECM synthesis.In the full-thickness OCD model of rabbit,CuTA@SF hydrogel displayed successfully in situ OCD regeneration,as evidenced by micro-CT,histology(HE,S/O,and toluidine blue staining)and immunohistochemistry(Col I and aggrecan immunostaining).Therefore,CuTA@SF hydrogel is a promising biomaterial targeted at the regeneration of OCD.
关 键 词:Osteochondral regeneration Metal-organic framework Nanozyme INFLAMMATION ROS SILK
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