The use of poly(N-isopropylacrylamide)-g-poly(ethylene glycol) as an injectable scaffold for repair of the injured spinal cord

Spinal cord injury (SCI) typically results in permanent functional loss. In order to repair the damaged tissue following SCI and to promote functional recovery, the non-permissive injury environment needs to be adjusted by modulating the immune reaction that follows the initial injury and leads to inflammation and expansion and also by replacing lost or damaged cells. This work investigates the feasibility of using an injectable hydrogel, based on poly(N-isopropylacryalmide) (PNIPAAm), lightly crosslinked with poly(ethylene glycol) (PEG), to serve as an injectable scaffold for local delivery of neurotrophins and cells into the injured spinal cord.This work tests the biocompatibility of the PNIPAAm-g-PEG scaffold by evaluating its ability to be injected as a viscous liquid, forming a space filling gel, and for its ability to support cell survival, without contributing to an injury-related inflammatory response. The scaffold was also evaluated for its ability to promote axonal growth through the action of released brain-derived neurotrophic factor (BDNF).Other studies include development of a device that uses sustained-release microspheres for delivery of growth factors and enzymes to the injured spinal cord. BDNF, which stimulates axon growth, was encapsulated in a polymer and combined with the PNIPAAm-g-EG scaffold. In addition, the enzyme chondroitinase (ChABC), which digests inhibitory proteoglycans that form the glial scar, has been shown to promote axonal growth past the lesion. ChABC was also encapsulated in sustainedrelease microparticles, in an attempt to stabilize the protein so it can effectively digest proteoglycans.By incorporating the most effective techniques, the final study in this work tested this delivery device in a comprehensive in vivo animal study. Animals were evaluated for the ability to recover from sensorimotor forelimb deficits associated with a cervical dorsolateral funiculotomy. Animals were analyzed in various behavioral tests prior to SCI and following SCI to assess the initial loss and potential gain of sensorimotor function over time. The ability of this multifunctional scaffold to mimic the host spinal tissue and to deliver cellular grafts and growth factors to the site of an injury, without a significant immune response, will provide a permissive niche for axonal regeneration, eventually leading to complete functional recovery.Ph.D., Chemical Engineering -- Drexel University, 201