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A modified collagen scaffold facilitates endogenous neurogenesis for acute spinal cord injury repair

机译:修饰的胶原蛋白支架促进了急性脊髓损伤修复的内源神经发生

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摘要

Graphical abstract Display Omitted Abstract Due to irreversible neuronal loss and glial scar deposition, spinal cord injury (SCI) ultimately results in permanent neurological dysfunction. Neuronal regeneration of neural stem cells (NSCs) residing in the spinal cord could be an ideal strategy for replenishing the lost neurons and restore function. However, many myelin-associated inhibitors in the SCI microenvironment limit the ability of spinal cord NSCs to regenerate into neurons. Here, a linearly ordered collagen scaffold was used to prevent scar deposition, guide nerve regeneration and carry drugs to neutralize the inhibitory molecules. A collagen-binding EGFR antibody Fab fragment, CBD-Fab, was constructed to neutralize the myelin inhibitory molecules, which was demonstrated to promote neuronal differentiation and neurite outgrowth under myelin in vitro . This fragment could also specifically bind to the collagen and undergo sustained release from collagen scaffold. Then, the scaffolds modified with CBD-Fab were transplanted into an acute rat SCI model. The robust neurogenesis of endogenous injury-activated NSCs was observed, and these NSCs could not only differentiate into neurons but further mature into functional neurons to reconnect the injured gap. The results indicated that the modified collagen scaffold could be an ideal candidate for spinal cord regeneration after acute SCI. Statements of Significance A linearly ordered collagen scaffold was specifically modified with collagen-binding EGFR antibody, allowed for sustained release of this EGFR neutralizing factor, to block the myelin associated inhibitory molecules and guide spinal cord regeneration along its linear fibers. Dorsal root ganglion neurons and neural stem cells induced by CBD-Fab exhibited enhanced neurite outgrowth and neuronal differentiation rate under myelin in vitro . Transplantation of the modified collagen scaffold with moderate EGFR neutralizing proteins showed greatest advantage on endogenous neurogenesis of injury-activated neural stem cells for acute spinal cord injury repair.
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著录项

  • 来源
    《Acta biomaterialia》 |2017年第1期|共13页
  • 作者单位

    Key Laboratory for Nano-Bio Interface Research Division of Nanobiomedicine Suzhou Institute of;

    State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental;

    State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental;

    State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental;

    Key Laboratory for Nano-Bio Interface Research Division of Nanobiomedicine Suzhou Institute of;

    State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental;

    State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental;

    Key Laboratory for Nano-Bio Interface Research Division of Nanobiomedicine Suzhou Institute of;

    Key Laboratory for Nano-Bio Interface Research Division of Nanobiomedicine Suzhou Institute of;

    State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental;

    University of Chinese Academy of Sciences;

    University of Chinese Academy of Sciences;

    Key Laboratory for Nano-Bio Interface Research Division of Nanobiomedicine Suzhou Institute of;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 普通生物学;
  • 关键词

    Collagen scaffold; EGFR neutralizing factor; Controlled release; Spinal cord injury; Neurogenesis;

    机译:胶原屑脚手架;EGFR中和因子;控释;脊髓损伤;神经发生;

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