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The use of poly(N-isopropylacrylamide)-g-poly(ethylene glycol) branched copolymer as an injectable scaffold for local delivery of neurotrophins and cellular transplants into the injured spinal cord Lauren Conova Advisor: Anthony Lowman Biomaterials and Drug Delivery Laboratory in collaboration with Drexel College of Medicine, Department of Neurobiology and Anatomy Abstract Injuries to the central nervous system (CNS) typically result in permanent functional loss. Most functional deficits after spinal cord injury (SCI) result from the interruption of descending and ascending axons and the lack of their successful regeneration. The failure of axons to regenerate is partially attributed to the non-permissive environment of the adult mammalian CNS. In order to promote functional recovery following SCI, the non-permissive injury environment needs to be modified by providing neuroprotection to prevent neuronal loss; by reducing the glial scar, by modulating the immune response; and by potentially replacing lost or damaged cells. Therapeutic strategies, such as the delivery of neurotrophic factors and cellular transplants, in combination with matrices or scaffolds, have emerged as treatment options for SCI. This project examines the use of an injectable hydrogel, based on poly(N-isopropylacryalmide) (PNIPAAm), lightly crosslinked with poly(ethylene glycol) (PEG), to serve as a scaffold in an in vivo rodent model of SCI. This hydrogel provides structural support and can be injected as a viscous liquid into an injury site, where it transitions to form a spacefilling gel. Specifically, the primary aims of this project are to assess the biocompatibility of the scaffold by evaluating graft cell survival and the host tissue immune response. The scaffold is also evaluated for its ability to promote axonal growth through the action of released brainderived neurotrophic factor (BDNF). Preliminary experiments have shown that the scaffold does not contribute to an injury-related inflammatory response. PNIPAAm-g-PEG has also shown to be an effective vehicle for delivery of cellular transplants and supports graft survival. Additionally, PNIPAAm-g-PEG is permissive to axonal growth and can serve as an injectable scaffold for local delivery of BDNF.