(686d) Development of Nano and Microparticles as a Growth Factor Delivery System

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 and provide a bridge for axon growth. The main limitation towards the success of a PNG is the inability of the axons to re-enter the spinal cord tissue and grow towards existing axons. Growth factors, such as BDNF and NT-3 have been shown to help promote axon growth and regeneration post injury. By developing a nano/micro-particulate delivery system, a controlled release of these trophic factors can be created. Injection(s) of particles will allow for the creation of a growth factor concentration gradient through either a single injection allowing for the natural diffusion of different sized particles within the spinal tissue or through multiple injections. The gradient will allow for the directional cues necessary for directional growth of axons towards existing axons. 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) (PEG). Variations in the fabrication process are 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.