(65am) Biomaterials for Drug Delivery to the Injured Spinal Cord

Spinal cord injury (SCI) affects nearly 250,000 Americans with an estimated additional 10,000 cases per year (NIH, 2001). The vast majority of these cases are young adults in their early twenties, who face enormous physical challenges with no treatment currently available. In addition, long-term care of these patients creates an overwhelming financial burden on the healthcare system. In order to successfully repair the lost and damaged tissue following SCI and promote functional recovery, a number of problems need to be solved: (1) Survival of nervous tissue needs to be increased and lost cells need to be replaced; (2) The glial scar which is created after the injury and serves as a barrier to axonal growth must be dissolved; (3) The immune reaction that follows the initial injury and leads to inflammation and secondary injury has to be modulated and finally, (4) Regenerating axons must be guided to their target cells to form functional synapses.

Most current designs for spinal cord repair after an injury focus on replacement of cells using either a polymeric or cellular based scaffold design. The goal of this research is to expand the use of biomaterials to address the prevention of inflammation and secondary injury as well as to provide axonal guidance. The first part can be achieved using thin polymeric films that release anti-inflammatory drugs over a 3-5 day period locally to the injury site. These films can be made from either a non-degradable material that would need to be later removed (poly vinyl alcohol ? poly vinyl pyrollidone), or ideally a degrading poly lactic glycolic acid (PLGA) that would not require a second surgery.

Research has shown that axons will respond to specific neurotrophins (NT-3, BDNF and GDNF) and grow towards increasing concentrations of them (Taylor et al, 2006). It is therefore believed that if increasing gradients of BDNF could be created beyond the cellular or scaffold replacement at the injury site, then the axons could be guided back into the uninjured tissue to remake the necessary connections for functional recovery. The goal of this project is to create increasing gradients of BDNF that can be sustained over time in vivo after a spinal cord injury. The BDNF is encapsulated in a degradable polymeric (poly-lactic-acid) microparticle. These microparticles degrade slowly over 6-8 weeks when injected into tissue, allowing a controlled release of the BDNF over time. Injections at increasing concentrations moving away from the injury site can create BDNF gradients in the tissue that can be sustained for 6-8 weeks. This should allow for the regenerating or replaced axons to reconnect with uninjured tissue leading to functional recovery after a spinal cord injury. These microparticles can then be implemented along with any promising axonal replacement or regeneration design for the injury site allowing increased chances for recovery.

Taylor L, L. Jones, M. Tuszynski, A. Blesch. ?Neurotrophin-3 Gradients Established by Lentiviral Gene Delivery Promote Short-Distance Axonal Bridging beyond? Cellular Grafts in the Injured Spinal Cord J Neurosci 2006;26(38):9713-9721.