Download g as an injectable scaffold for local delivery of neurotrophins and... transplants into the injured spinal cord

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.