Nano neuro knitting: Peptide nanofiber scaffold for brain repair and axon regeneration with functional return of vision

  1. Rutledge G. Ellis-Behnke*,,,§,
  2. Yu-Xiang Liang,,
  3. Si-Wei You,
  4. David K. C. Tay,,,
  5. Shuguang Zhang,
  6. Kwok-Fai So,,§, and
  7. Gerald E. Schneider*
  1. *Department of Brain and Cognitive Science and
  2. Center for Biomedical Engineering, Massachusetts Institute of Technology, 77 Massachusett Avenue, Cambridge, MA 02139-4307;
  3. Department of Anatomy, University of Hong Kong Li Ka Shing Faculty of Medicine and
  4. State Key Laboratory of Brain and Cognitive Sciences, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China; and
  5. Institute for Neuroscience, Fourth Military Medical University, 17 Changle West Road, Xi’an 710032, People’s Republic of China
  1. Communicated by D. Carleton Gajdusek, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France, January 23, 2006 (received for review November 9, 2005)

Abstract

Nanotechnology is often associated with materials fabrication, microelectronics, and microfluidics. Until now, the use of nanotechnology and molecular self assembly in biomedicine to repair injured brain structures has not been explored. To achieve axonal regeneration after injury in the CNS, several formidable barriers must be overcome, such as scar tissue formation after tissue injury, gaps in nervous tissue formed during phagocytosis of dying cells after injury, and the failure of many adult neurons to initiate axonal extension. Using the mammalian visual system as a model, we report that a designed self-assembling peptide nanofiber scaffold creates a permissive environment for axons not only to regenerate through the site of an acute injury but also to knit the brain tissue together. In experiments using a severed optic tract in the hamster, we show that regenerated axons reconnect to target tissues with sufficient density to promote functional return of vision, as evidenced by visually elicited orienting behavior. The peptide nanofiber scaffold not only represents a previously undiscovered nanobiomedical technology for tissue repair and restoration but also raises the possibility of effective treatment of CNS and other tissue or organ trauma.

Footnotes

  • §To whom correspondence may be addressed. E-mail: rutledg{at}mit.edu or hrmaskf{at}hkucc.hku.hk
  • Author contributions: R.G.E.-B., K.-F.S., and G.E.S. designed research; R.G.E.-B., Y.-X.L., S.-W.Y., and G.E.S. performed research; S.Z. contributed new reagents/analytic tools; R.G.E.-B., Y.-X.L., D.K.C.T., K.-F.S., and G.E.S. analyzed data; R.G.E.-B., K.-F.S., and G.E.S. wrote the paper; and K.-F.S. and G.E.S. provided financial support.

  • Conflict of interest statement: No conflicts declared.

  • ** Schneider, G. E., You, S., So, K. F., Carter, D. A., Khan, F., Okobi, A. & Ellis-Behnke, R. (2000) Soc. Neurosci. Abstr. 26, 611.

  • Abbreviations:
    SAPNS,
    self-assembling peptide nanofiber scaffold;
    SC,
    superior colliculus;
    RADA,
    arginine, alanine, aspartate, and alanine;
    Pn,
    postnatal day n.
  • Freely available online through the PNAS open access option.

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