Fabrication of vascularized scaffolds for the treatment of spinal cord injury

The overall goal of the research presented here is to evaluate the efficacy of transplanting scaffolds containing central nervous system vasculature to repair spinal cord injury. There are three major phases of this effort: development of a three-dimensional model of central nervous system vasculature, transplantation of a pre-vascularized scaffold and optimization of the biomaterial used to deliver vasculature to the injured spinal cord. This research has produced the first ever compliant, three-dimensional (3D) blood-brain barrier (BBB) vessel. In order to create vascularized scaffolds appropriate for transplantation into a rat model of spinal cord injury, techniques to fabricate and spatially pattern capillary-scale vasculature that maintain the tight junction morphology characteristic of the BBB are described. Both in vitro experiments using neural precursor cells and in vivo studies using the rat model demonstrate that axons grow along the patterned microvasculature, which demonstrates the potential of harnessing neurovascular interaction as a novel strategy to regenerate the central nervous system. The third phase of the dissertation focuses on improving the biomaterial composition to enhance the infiltration of host axons into the scaffold. Specifically, the permissivity of a RADA-16I nanofiber peptide material is evaluated by measuring axon growth and levels of serotonin receptors within the scaffold. Taken together, this work advances the field of tissue engineering and regenerative medicine by demonstrating the potential of vascularized scaffolds to repair the damaged spinal cord.