Acellular nerve xenografts based on supercritical extraction technology for repairing long-distance sciatic nerve defects in rats  

作　　者：Shuai Wei Qian Hu Jianxiong Ma Xiu Dai Yu Sun Gonghai Han Haoye Meng Wenjing Xu Lei Zhang Xinlong Ma Jiang Peng Yu Wang 

机构地区：[1]Tianjin Hospital,Tianjin University,No.406 Jiefang South Road,Hexi District,Tianjin,300211,China [2]Institute of Orthopedics,The First Medical Center,Chinese PLA General Hospital,Beijing Key Lab of Regenerative Medicine in Orthopedics,Key Laboratory of Musculoskeletal Trauma and War Injuries PLA,No.28 Fuxing Road,Haidian District,Beijing 100853,China [3]Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education,Neural Regeneration Co-Innovation Center of Jiangsu Province,Nantong University,No.19 Qixiu Road,Chongchuan District,Nantong,226001,China [4]Department of Geriatrics,The Second People’s Hospital of Nantong,Affiliated Rehabilitation Hospital of Nantong University,No.298 Xinhua Road,Chongchuan District,Nantong,226006,China [5]Institute of Orthopedics,Tianjin Hospital Tianjin University,Tianjin Key Laboratory of Orthopedic Biomechanics and Medical Engineering,No.155 Munan Road,Heping District,Tianjin,300050,China [6]The First People’s Hospital of Yunnan Province,No.157 Jinbi Road,Xishan District,Kunming,650034,China [7]Academy of Medical Engineering and Translational Medicine,Tianjin University,No.92 Weijin Road,Nankai District,Tianjin,300072,China

出　　处：《Bioactive Materials》2022年第12期300-320,共21页生物活性材料（英文）

基　　金：the National Key R&D Program of China(2019YFA0110704);Medical Research and Development Projects(AWS17J005);the National Key R&D Program of China(2017YFA0104702);we are very grateful to the professional supercritical extraction equipment and technical support provided by Joel Hi-Tech(Dalian,China)Co.,Ltd.

摘　　要：Compared to conventional artificial nerve guide conduits (NGCs) prepared using natural polymers or synthetic polymers, acellular nerve grafts (ACNGs) derived from natural nerves with eliminated immune components have natural bionic advantages in composition and structure that polymer materials do not have. To further optimize the repair effect of ACNGs, in this study, we used a composite technology based on supercritical carbon dioxide (scCO_(2)) extraction to process the peripheral nerve of a large mammal, the Yorkshire pig, and obtained an innovative Acellular nerve xenografts (ANXs, namely, CD + scCO_(2) NG). After scCO_(2) extraction, the fat and DNA content in CD + scCO_(2) NG has been removed to the greatest extent, which can better supported cell adhesion and proliferation, inducing an extremely weak inflammatory response. Interestingly, the protein in the CD + scCO_(2) NG was primarily involved in signaling pathways related to axon guidance. Moreover, compared with the pure chemical decellularized nerve graft (CD NG), the DRG axons grew naturally on the CD + scCO_(2) NG membrane and extended long distances. In vivo studies further revealed that the regenerated nerve axons had basically crossed the CD + scCO_(2) NG 3 weeks after surgery. 12 weeks after surgery, CD + scCO_(2) NG was similar to autologous nerves in improving the quality of nerve regeneration, target muscle morphology and motor function recovery and was significantly better than hollow NGCs and CD NG. Therefore, we believe that the fully decellularized and fat-free porcine ACNGs may be the most promising “bridge” for repairing human nerve defects at this stage and for some time to come.

关 键 词：Peripheral nerve regeneration Acellular nerve xenograft Supercritical extraction Peripheral nerve injury Nerve defect 

分 类 号：R318.08[医药卫生—生物医学工程] R745[医药卫生—基础医学]