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The Journal of Neuroscience, April 2, 2008, 28(14):3814-3823; doi:10.1523/JNEUROSCI.0143-08.2008

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Development/Plasticity/Repair
Self-Assembling Nanofibers Inhibit Glial Scar Formation and Promote Axon Elongation after Spinal Cord Injury

Vicki M. Tysseling-Mattiace,1 * Vibhu Sahni,1 * Krista L. Niece,3 Derin Birch,1 Catherine Czeisler,1 Michael G. Fehlings,4 Samuel I. Stupp,2,3 and John A. Kessler1

1Department of Neurology and 2Department of Medicine and Institute for BioNanotechnology in Medicine, Northwestern University, Chicago, Illinois 60611, 3Departments of Materials Science and Engineering and Chemistry, Northwestern University, Evanston, Illinois 60208, and 4Department of Surgery, University of Toronto, Toronto, Ontario, Canada M5S 1A8

Correspondence should be addressed to Vicki M. Tysseling-Mattiace, 303 E. Chicago Avenue, Chicago, IL 60611. Email: v-mattiace{at}northwestern.edu

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.

Key words: spinal cord injury; nanotechnology; gliosis; regeneration; extracellular matrix; functional recovery

Received Nov. 1, 2007; revised March 5, 2008; accepted March 7, 2008.

Correspondence should be addressed to Vicki M. Tysseling-Mattiace, 303 E. Chicago Avenue, Chicago, IL 60611. Email: v-mattiace{at}northwestern.edu






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