(207e) Controlled Axon Regeneration In the Spinal Cord | AIChE

(207e) Controlled Axon Regeneration In the Spinal Cord


Coleman, J. - Presenter, Drexel University
Lowman, A. - Presenter, Drexel University

Spinal cord injury (SCI) affects over 250,000 Americans a year and current clinical solutions focus primarily on improving quality of life. SCI results from a physical tear or compression of spinal tissue causing damage to axons, potentially resulting in various levels of paralysis. One of the most promising and clinically relevant strategies for axon reconnection is surgical implantation of a peripheral nerve graft (PNG) to bypass the injury sight. The main limitation towards the success of a PNG is the inability of the nerve to reach and reconnect with existing nerves. Growth factors, such as BDNF and NT-3 have been shown to help promote axon growth and regeneration post injury. By developing novel nanoparticulate delivery systems, a controlled release of these trophic factors can be created. Preliminary biodistribution studies have shown that nanoparticles stereotaxically injected into the spinal tissue remain at the sight of injection. Injections of nanoparticles loaded with growth factors can be used to create a concentration gradient by injecting at several locations around the injury site as well as the PNG. The release profiles of the growth factors from the particles are modified to allow for the creation of the gradient. The gradient will allow for the directional cues necessary for connection of the implanted PNG to injured axons. In order for reconnection to occur, the PNG must grow towards the existing nerves for several weeks. Thus, the release rates of growth factors from the particles must range from hours to weeks. Release rates from the particles are controlled by varying the type of polymers used, the fabrication process and the degree and method of crosslinking within the particles. Examples of polymers used for particle formation include hydrophobic polymers such as poly (lactic acid) (PLA) and poly (lactic-co-glycolic acid) (PLGA) and hydrophilic polymers such as poly (ethylene glycol dimethacrylate) (PEGDM) and poly (vinyl alcohol) (PVA). Several types of emulsion fabrication process are used and polymer crosslinking is performed by both physical and chemical means. Nanoparticles will be modified to maximize growth factor loading, control release, maintain growth factor bioactivity, minimize macrophage uptake, and ultimately, cause directional nerve growth and reconnection in vivo.