The central nervous system (CNS) is a highly complex collection of specialized cells whose successful function relies on effective cellular communication to transport signal information across all the body's tissues and systems. Injury to these cells, whether through toxic molecules or processes, mechanical stresses, or age-related/genetic illnesses, leads to the breakdown of this communication and subsequent cell death. Regenerative medicine procedures to regain the functionality of the CNS after these insults is therefore of critical importance in the medical community. However, the fully developed CNS in the adult human body has limited capacity to regenerate tissues and to form these essential new cellular connections when lost. Among the great needs in this field are therapies to treat spinal cord injury (SCI) in order to prevent or reverse paralysis, novel treatments for stroke and neurodegenerative diseases, as well as strategies to recover the function of optic and auditory nerves. New therapies could profoundly enhance quality of life for individuals facing these problems and significantly reduce health care costs as well. For example, in the United States alone, SCI affects 12,000 individuals every year, and approximately 259,000 Americans currently live with the devastating effects of SCI. Novel therapeutic approaches to CNS regeneration will have significant impact on health care and patient well-being. In this renewal application three investigators, from the medical, chemical, and materials sciences, propose research to develop therapies for that could be used to prevent paralysis after spinal cord injury and also a different therapy that could be surgically implanted to reverse paralysis. The approach involves the use of especially designed molecules known as peptide amphiphiles that self-assemble in the spinal cord into nanofibers. These nanofibers carry biological signals that promote regeneration in the traumatized tissue, and biodegrade within weeks into harmless nutrients. The specific strategy involves the use of several peptide-based signals that emulate the effect of natural proteins, and also the delivery of genes that will lead to the production in the cord of regenerative growth factors. For acute injury the therapy takes the form of an injectable liquid, and for the chronic injury it consists of a pre-fabricated gel implant to be placed after removal of the glial scar in paralyzed patients. Both therapies will be tested in well established mouse models for spinal cord injury.

Public Health Relevance

In the United States approximately 12,000 new cases of spinal cord injury occur each year. Spinal cord injury is most often caused by accidents, it primarily affects young adults, and it is estimated that 259,000 Americans currently live with its devastating effects. This research proposal aims to develop therapies that could prevent or reverse paralysis after spinal cord injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB003806-07
Application #
8223140
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Hunziker, Rosemarie
Project Start
2004-09-04
Project End
2016-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
7
Fiscal Year
2012
Total Cost
$618,468
Indirect Cost
$200,782
Name
Northwestern University at Chicago
Department
Type
Organized Research Units
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Pazos, Elena; Sleep, Eduard; Rubert Pérez, Charles M et al. (2016) Nucleation and Growth of Ordered Arrays of Silver Nanoparticles on Peptide Nanofibers: Hybrid Nanostructures with Antimicrobial Properties. J Am Chem Soc 138:5507-10
Berns, Eric J; Álvarez, Zaida; Goldberger, Joshua E et al. (2016) A tenascin-C mimetic peptide amphiphile nanofiber gel promotes neurite outgrowth and cell migration of neurosphere-derived cells. Acta Biomater 37:50-8
Newcomb, Christina J; Sur, Shantanu; Lee, Sungsoo S et al. (2016) Supramolecular Nanofibers Enhance Growth Factor Signaling by Increasing Lipid Raft Mobility. Nano Lett 16:3042-50
North, Hilary A; Pan, Liuliu; McGuire, Tammy L et al. (2015) β1-Integrin alters ependymal stem cell BMP receptor localization and attenuates astrogliosis after spinal cord injury. J Neurosci 35:3725-33
Sur, Shantanu; Tantakitti, Faifan; Matson, John B et al. (2015) Epitope topography controls bioactivity in supramolecular nanofibers. Biomater Sci 3:530-532
Sur, Shantanu; Tantakitti, Faifan; Matson, John B et al. (2015) Epitope topography controls bioactivity in supramolecular nanofibers. Biomater Sci 3:520-32
Rubert Pérez, Charles M; Stephanopoulos, Nicholas; Sur, Shantanu et al. (2015) The powerful functions of peptide-based bioactive matrices for regenerative medicine. Ann Biomed Eng 43:501-14
Stephanopoulos, Nicholas; Freeman, Ronit; North, Hilary A et al. (2015) Bioactive DNA-peptide nanotubes enhance the differentiation of neural stem cells into neurons. Nano Lett 15:603-9
Boekhoven, Job; Zha, R Helen; Tantakitti, Faifan et al. (2015) Alginate-peptide amphiphile core-shell microparticles as a targeted drug delivery system. RSC Adv 5:8753-8756
Freeman, Ronit; Boekhoven, Job; Dickerson, Matthew B et al. (2015) Biopolymers and supramolecular polymers as biomaterials for biomedical applications. MRS Bull 40:1089-1101

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