This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Spinal cord injury (SCI) results in permanent motor and sensory deficits due to the inability of damaged axons to successfully regenerate in the adult central nervous system (CNS). The objective of this project is the development of acellular, biomaterial scaffolds to stimulate and direct axonal regeneration across SCI lesion sites, ultimately leading to re-innervation of distal target tissues and functional recovery. The biomaterial design will be modeled on the physical and biochemical mechanisms for axonal growth and guidance provided by supporting glial cell populations during CNS development and successful regeneration in the peripheral nervous system. Specifically, novel deep groove polymer fibers with micrometer-scale, parallel surface channels will provide topographic directional guidance for axonal regeneration. Slowly degrading hydrogel coatings will provide adhesive and trophic support for neuronal survival and axonal regeneration through protein and/or gene delivery of L1 neural cell adhesion molecule and neurotrophin-3 (NT-3). Our overall hypothesis is that biomaterials synergistically incorporating topographic, adhesive, and trophic stimuli will achieve levels of bioactivity for in vitro and in vivo axonal regeneration comparable to olfactory ensheathing glia (OEG), one of the most effective cell types for transplantation studied to date.
Specific aims are * To create acellular scaffolds for axonal regeneration integrating topographic, adhesive, and trophic bioactivity * To evaluate the bioactivity of engineered biomaterial fibers relative to OEG * To directly compare anatomical regeneration elicited by engineered biomaterials and OEG in a rat dorsal hemisection injury model Relative to many transplantation-based approaches, biomaterial scaffolds offer reproducibility, immunological compatibility, and may be packaged and stably stored for extended periods, suggesting the potential for an """"""""off-the-shelf"""""""" therapy.
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