title: A modified collagen scaffold facilitates endogenous neurogenesis for acute spinal cord injury repair.
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.
  
  
  
  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.
authors.affiliation: Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China; University of Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yannan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Han
authors.affiliation: Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China; University of Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Bai
authors.initials: B
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Nuo
authors.initials: N
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Sumei
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Xue
authors.affiliation: Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China; State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: jwdai@genetics.ac.cn.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002921:Cicatrix / Q000473:pathology; D003094:Collagen / Q000494:pharmacology*; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D009457:Neuroglia / Q000473:pathology; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D058630:Spinal Cord Regeneration / Q000187:drug effects*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D007140:Immunoglobulin Fab Fragments; D011993:Recombinant Fusion Proteins; D003094:Collagen; D066246:ErbB Receptors
keywords: Collagen scaffold; Controlled release; EGFR neutralizing factor; Neurogenesis; Spinal cord injury