(256b) Engineering a Multifunctional Scaffold for Spinal Cord Repair

Spinal cord injury (SCI) is a devastating condition affecting nearly a quarter of a million Americans. The majority of SCI victims are young adults who are often left with life long injuries including paralysis, respiratory, bowel and bladder dysfunctions. What makes these injuries so devastating is the inability of the central nervous system (CNS) to regenerate the severed axons and blood vessels. Current treatment options for SCI focus mainly on relieving the compression on the spinal column and treatment of the symptoms. The goal of this project is to create a non-degradable scaffold as a drug delivery device that would provide mechanical stabilization and a protected environment for the regeneration of neurons and blood vessels post spinal cord injury. The scaffold proposed is a hydrogel made from poly (2-hyrdroxy-ethylmethacrylate) grafted with poly (ethylene glycol). Each of these polymers have been used in biomaterial application and have been shown to be biocompatible. Biodegradable poly (lactic acid) or poly (lactic-co-glycolic acid) microparticles loaded with therapeutic proteins to promote regeneration of neurons and blood vessels are incorporated into the scaffold. The microparticles allow a controlled, sustainable release of these proteins into the local tissue. Preliminary work has shown that the protein-loaded microparticles have been successfully entrapped into the hydrogel matrix and tailoring of the mechanical properties can be achieved by varying the solvent to polymer ratio. Hydrogels polymerized in 70-75% solvent match the compressive modulus range of the spinal cord gray matter when made via redox initiated free radical polymerization. Addition of microparticles to the polymerization mixture decreases the free volume for reaction and creates an edge effect making the mechanical properties of the gel drastically different. The synthesis of the scaffold containing microparticles will need to be adapted in order to match the mechanical properties of the gray matter is crucial in its realizability as an implant. Altering the microparticle polymer composition (specifically the ratio of the lactic acid to glycolic acid) as well as the microparticle size and drug composition can be used to control the release profile. It is critical to maintain the biological activity of the therapeutic proteins while manipulating, fabricating, and releasing the drug from the microparticles.