In the United States alone, there are almost 1 million persons with damaged spinal cords; at least 42,000 are veterans. Spinal cord injury (SCI) is a devastating condition for which there is no cure. Bioengineering efforts have been focused on developing biomaterials that promote the regeneration of axons across lesions. Although these materials show promise, directing the axons from the conduit back into the spinal cord to integrate with host pathways remains to be achieved. Creating permissive caudal interfaces for axonal growth may restore neural connections between supraspinal centers and the cord required for control of locomotor and autonomic functions. Recent efforts, therefore, have been exploring combination strategies using conduits with cells and/or neurotrophic or neuroprotective factors. The goal here is to improve axon regeneration across a Schwann cell (SC) bridge graft and into the spinal parenchyma caudal to the injury to improve functional recovery by using a novel tissue engineering strategy. These studies bring together the Principal Investigator, Dr. Treena Livingston Arinzeh, who has expertise in tissue engineering and biomaterials, with an established investigator in SCI research, Dr. Mary Bartlett Bunge, to develop a novel, combination strategy and more translatable approach in spinal cord repair. A piezeoelectric conduit made of polyvinylidene fluoridetrifluoroethylene (PVDF-TrFE), which has intrinsic electrical properties and proven biocompatibility (PVDF-TrFE is Food and Drug Administration [FDA] approved), will be combined with SCs and neurotrophin delivery. Our overall hypothesis is that axonal regeneration and functional recovery can be improved in SCI by utilizing a SC conduit that provides electrical activity and will release neurotrophins at and caudal to the injury site. The neurotrophin biomaterial delivery vehicle will be placed on top of the spinal cord, without injuring the cord. Two specific aims will be addressed. Aim 1 will evaluate the piezoelectric conduits with SCs for axonal growth with and without Matrigel. Aim 2 will determine if axons extend into the caudal spinal parenchyma following the controlled release of neurotrophins at and below the SC conduit and improve functional recovery. This project addresses a Fiscal Year 2013 Area of Encouragement, functional deficits during the first year after SCI. The unique combination of SC transplantation in a piezoelectric conduit with neurotrophin delivery both from the conduit and by delivery beyond the conduit, may be a more effective and translatable strategy leading to clinical trials addressing injuries from explosions, motor vehicle and gunshot accidents that not only civilians but also military personnel receive in combat zones. Dr. Bunge and The Miami Project are conducting a Phase I clinical trial for autologous human SC transplantation for subacute SCI. Studies proposed here will complement this trial by developing novel SC combination strategies to improve functional recovery. If findings in the proposed animal studies show promise, the path to a clinical trial will be faster since SCs are currently in an FDA-approved clinical trial and the proposed biomaterials for growth factor delivery also have been approved by the FDA.
|Effective start/end date||9/30/14 → 9/29/17|
- Congressionally Directed Medical Research Programs: $622,243.00