Chitosan/PLGA-based tissue engineered nerve grafts with SKP-SC-EVs enhance sciatic nerve regeneration in dogs through miR-30b-5p-mediated regulation of axon growth  

作　　者：Miaomei Yu Mi Shen Daiyue Chen Yan Li Qiang Zhou Chunyan Deng Xinyang Zhou Qi Zhang Qianru He Hongkui Wang Meng Cong Haiyan Shi Xiaosong Gu Songlin Zhou Fei Ding 

机构地区：[1]Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education,Co-Innovation Center of Neuroregeneration,NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products,Nantong University,Nantong,Jiangsu,226001,China [2]Clinical Medical Research Center,The Third Affiliated Hospital of Soochow University,Changzhou,Jiangsu,213003,China [3]Department of Pathophysiology,School of Medicine,Nantong University,Nantong,Jiangsu,226001,China

出　　处：《Bioactive Materials》2024年第10期378-395,共18页生物活性材料（英文）

基　　金：supported by the Major Research Plan of the National Natural Science Foundation of China(92068112);the National Key Research and Development Program of China(2017YFA0104700);the National Natural Science Foundation of China(82201509);the National Major Project of Research and Development(2022YFA1105500).

摘　　要：Extracellular vesicles from skin-derived precursor Schwann cells(SKP-SC-EVs)promote neurite outgrowth in culture and enhance peripheral nerve regeneration in rats.This study aimed at expanding the application of SKPSC-EVs in nerve grafting by creating a chitosan/PLGA-based,SKP-SC-EVs-containing tissue engineered nerve graft(TENG)to bridge a 40-mm long sciatic nerve defect in dogs.SKP-SC-EVs contained in TENGs significantly accelerated the recovery of hind limb motor and electrophysiological functions,supported the outgrowth and myelination of regenerated axons,and alleviated the denervation-induced atrophy of target muscles in dogs.To clarify the underlying molecular mechanism,we observed that SKP-SC-EVs were rich in a variety of miRNAs linked to the axon growth of neurons,and miR-30b-5p was the most important among others.We further noted that miR-30b-5p contained within SKP-SC-EVs exerted nerve regeneration-promoting effects by targeting the Sin3a/HDAC complex and activating the phosphorylation of ERK,STAT3 or CREB.Our findings suggested that SKP-SC-EVs-incorporating TENGs represent a novel type of bioactive material with potential application for peripheral nerve repair in the clinic.

关 键 词：Peripheral nerve regeneration Skin-derived precursor Schwann cells Extracellular vesicles Tissue engineered nerve graft miR-30b-5p Sin3a/HDAC complex 

分 类 号：R318[医药卫生—生物医学工程]