Self-Assembling Nanofibers Inhibit Glial Scar Formation and Promote Axon Elongation after Spinal Cord Injury
By V. M. Tysseling-Mattiace, Vibhu Sahni, Krista L. Niece, Derin V. Birch, C. Czeisler, M. Fehlings, Samuel I. Stupp, J. Kessler. Journal of Neuroscience, 2008
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Peptide amphiphile (PA) molecules that self-assemble in vivo into supramolecular nanofibers were used as a therapy in a mouse model of spinal cord injury (SCI). Because self-assembly of these molecules is triggered by the ionic strength of the in vivo environment, nanoscale structures can be created within the extracellular spaces of the spinal cord by simply injecting a liquid. The molecules are designed to form cylindrical nanofibers that display to cells in the spinal cord the laminin epitope IKVAV at nearly van der Waals density. IKVAV PA nanofibers are known to inhibit glial differentiation of cultured neural stem cells and to promote neurite outgrowth from cultured neurons. In this work, in vivo treatment with the PA after SCI reduced astrogliosis, reduced cell death, and increased the number of oligodendroglia at the site of injury. Furthermore, the nanofibers promoted regeneration of both descending motor fibers and ascending sensory fibers through the lesion site. Treatment with the PA also resulted in significant behavioral improvement. These observations demonstrate that it is possible to inhibit glial scar formation and to facilitate regeneration after SCI using bioactive three-dimensional nanostructures displaying high densities of neuroactive epitopes on their surfaces.
Subfields: Biomaterials, Cellular and Molecular Neuroscience, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/e2b8191663b23b6e17a387acfa87288dbe7e9922
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Citations in the corpus
- Neural tissue engineering options for peripheral nerve regeneration. (2014, methodology): “Diverse manufacturing methods, such as electrospinning [104,105], phase separation [106,107], and self-assembly [108,109], as well as computer-aided design-based fabrication techniques [19], have been used for preparing nanostructured”
- Random versus directionally persistent cell migration (2009, background): “Fibrillar topographical cues in the form of 1D nanofibres can guide axonal growth and glial cell migration in vivo”