N‑Cadherin‑Functionalized Nanofiber Hydrogel Facilitates Spinal Cord Injury Repair by Building a Favorable Niche for Neural Stem Cells  

作　　者：Kaiyuan Yang Jia Yang Weitao Man Zhe Meng Chun‑Yi Yang Zheng Cao Jun Liu Kunkoo Kim Yaosai Liu Shuhui Yang Yi Guo Zhijun He Chao Ma Guihuai Wang Xiumei Wang 

机构地区：[1]State Key Laboratory of New Ceramics and Fine Processing,Key Laboratory of Advanced Materials,School of Materials Science and Engineering,Tsinghua University,Beijing 100084,China [2]Department of Neurosurgery,Beijing Tsinghua Changgung Hospital,School of Clinical Medicine,Tsinghua University,Beijing 102218,China [3]School of Materials Science and Engineering,Zhejiang‑Mauritius Joint Research Center for Biomaterials and Tissue Engineering,Zhejiang Sci-Tech University,Hangzhou 310018,China

出　　处：《Advanced Fiber Materials》2023年第4期1349-1366,共18页先进纤维材料（英文）

基　　金：National Natural Science Foundation of China(Grant Nos.32271414 and 82201521);Tsinghua Precision Medicine Foundation(Grant No.2022TS001);National Key Research and Development Program of China(Grant No.2020YFC1107600).

摘　　要：The inhospitable niche at the injury site after spinal cord injury(SCI)brings several challenges to neural stem cell(NSC)therapy,such as limited NSC retention and neuronal differentiation.Biomaterial-based stem cell transplantation has become a promising strategy for building a favorable niche to stem cells.Herein,an aligned fibrin nanofiber hydrogel modified with N-Cadherin-Fc(AFGN)was fabricated by electrospinning and biochemical conjugation to deliver NSCs for SCI repair.The AFGN hydrogel provides multimodal cues,including oriented nanofibrous topography,soft stiffness,and specific cell binding ligand,for directing NSC functions and nerve regeneration.The conjugated N-Cadherin-Fc recapitulated the homo-philic cell-cell interaction for NSCs’adhesion on AFGN and modulated cellular mechanosensing in response to AFGN for NSC differentiation.In addition,the AFGN hydrogel carrying exogenous NSCs was implanted in a rat 2 mm-long complete transected SCI model and significantly promoted the grafted NSCs retention,immunomodulation,neuronal differentiation,and in vivo integration with inherent neurons,thus finally achieved renascent neural relay formation and an encouraging locomotor functional recovery.Altogether,this study represents a valuable strategy for boosting NSC-based therapy in SCI regeneration by engineering an NSC-specific niche.

关 键 词：N-CADHERIN Aligned fibrin nanofiber scaffold NICHE Neural stem cell Spinal cord injury 

分 类 号：R651.2[医药卫生—外科学]