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Nanoladders Facilitate Directional Axonal Outgrowth and Regeneration

  • Yimin Huang
    Yimin Huang
    Department of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, United States
    More by Yimin Huang
  • Ying Jiang
    Ying Jiang
    Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, Massachusetts 02215, United States
    More by Ying Jiang
  • Qiuyu Wu
    Qiuyu Wu
    Department of Biological Sciences, Purdue University, 915 W. State Street, West Lafayette, Indiana 47907, United States
    More by Qiuyu Wu
  • Xiangbing Wu
    Xiangbing Wu
    Stark Neurosciences Research Institute, Indiana University School of Medicine, 320 W. 15th Street, Indianapolis, Indiana 46202, United States
    More by Xiangbing Wu
  • Xingda An
    Xingda An
    Department of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, United States
    More by Xingda An
  • Alexander A. Chubykin
    Alexander A. Chubykin
    Department of Biological Sciences, Purdue University, 915 W. State Street, West Lafayette, Indiana 47907, United States
  • Ji-Xin Cheng*
    Ji-Xin Cheng
    Department of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, United States
    Department of Electrical and Computer Engineering, Boston University, 8 St Mary’s Street, Boston, Massachusetts 02215, United States
    Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, Massachusetts 02215, United States
    *E-mail: [email protected]
    More by Ji-Xin Cheng
  • Xiao-Ming Xu*
    Xiao-Ming Xu
    Stark Neurosciences Research Institute, Indiana University School of Medicine, 320 W. 15th Street, Indianapolis, Indiana 46202, United States
    *E-mail: [email protected]
    More by Xiao-Ming Xu
  • , and 
  • Chen Yang*
    Chen Yang
    Department of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, United States
    Department of Electrical and Computer Engineering, Boston University, 8 St Mary’s Street, Boston, Massachusetts 02215, United States
    *E-mail: [email protected]
    More by Chen Yang
Cite this: ACS Biomater. Sci. Eng. 2018, 4, 3, 1037–1045
Publication Date (Web):February 17, 2018
https://doi.org/10.1021/acsbiomaterials.7b00981
Copyright © 2018 American Chemical Society

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    Abstract

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    After injuries, axonal regeneration over long distance is challenging due to lack of orientation guidance. Biocompatible scaffolds have been used to mimic the native organization of axons to guide and facilitate axonal regeneration. Those scaffolds are of great importance in achieving functional connections of the nervous system. We have developed a nanoladder scaffold to guide directional outgrowth and facilitate regeneration of axons. The nanoladders, composed of micron-scale stripes and nanoscale protrusions, were fabricated on the glass substrate using photolithography and reactive ion etching methods. Embryonic neurons cultured on the nanoladder scaffold showed significant neurite elongation and axonal alignment in parallel with the nanoladder direction. Furthermore, the nanoladders promoted axonal regeneration and functional connection between organotypic spinal cord slices over 1 mm apart. Multimodality imaging studies revealed that such neuronal regeneration was supported by directional outgrowth of glial cells along nanoladders in the organotypic spinal cord slice culture as well as in the coculture of glial cells and neurons. These results collectively herald the potential of our nanoladder scaffold in facilitating and guiding neuronal development and functional restoration.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsbiomaterials.7b00981.

    • SEM images of embryonic neuron cultured on nanoprotrusions; fabrication process; pattern design and SEM images of neurons cultured on micronstripe; cross-sectional SEM images of nanoladder; electrophysiology experimental setting and LFP curves; IF and SRS images of spinal cord tissue slices; and SEM images of spinal cord tissue slices cultured on nanoladder (PDF)

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    Cited By

    This article is cited by 5 publications.

    1. Lester Uy Vinzons, Shu-Ping Lin. Hierarchical Micro-/Nanotopographies Patterned by Tandem Nanosphere Lens Lithography and UV–LED Photolithography for Modulating PC12 Neuronal Differentiation. ACS Applied Nano Materials 2022, 5 (5) , 6935-6953. https://doi.org/10.1021/acsanm.2c00938
    2. Yingjun Lin, Juntao Wang, Xiangwen Liu, Yangfan Hu, Yong Zhang, Faqin Jiang. Synthesis, biological activity evaluation and mechanism analysis of new ganglioside GM3 derivatives as potential agents for nervous functional recovery. European Journal of Medicinal Chemistry 2024, 10 , 116108. https://doi.org/10.1016/j.ejmech.2023.116108
    3. Lester Uy Vinzons, Guo-Chung Dong, Shu-Ping Lin. Hierarchically patterned polyurethane microgrooves featuring nanopillars or nanoholes for neurite elongation and alignment. Beilstein Journal of Nanotechnology 2023, 14 , 1157-1168. https://doi.org/10.3762/bjnano.14.96
    4. Yimin Huang, Vincent Fitzpatrick, Nan Zheng, Ran Cheng, Heyu Huang, Chiara Ghezzi, David L. Kaplan, Chen Yang. Self‐Folding 3D Silk Biomaterial Rolls to Facilitate Axon and Bone Regeneration. Advanced Healthcare Materials 2020, 9 (18) https://doi.org/10.1002/adhm.202000530
    5. Hanna Liliom, Panna Lajer, Zsófia Bérces, Bence Csernyus, Ágnes Szabó, Domonkos Pinke, Péter Lőw, Zoltán Fekete, Anita Pongrácz, Katalin Schlett. Comparing the effects of uncoated nanostructured surfaces on primary neurons and astrocytes. Journal of Biomedical Materials Research Part A 2019, 107 (10) , 2350-2359. https://doi.org/10.1002/jbm.a.36743

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