Design, fabrication, and testing of a bioprinted nerve graft

Abstract

Injuries to nerves vary in their consequences, from weakened sensation and motor function to partial or complete paralysis. In the latter case, affecting about twenty thousand Americans yearly, the injury is debilitating and results in a significant decrease in quality of life. Currently there is no effective treatment for damage to the central nervous system, in particular the spinal cord. Compared to the injuries to the central nervous system, damage in the peripheral nerves, is more common, with about sixty thousand occurrences annually. The cost of associated surgical procedures and due to loss of function is in the billions. In this thesis we present work towards the construction and testing of a fully cellular, patented nerve graft, one amongst the first of its kind. For the fabrication of the graft we are the first to employ bioprinting (either implemented through a special purpose 3D bioprinter or manually), a novel tissue engineering method rapidly gaining acceptance and utility. We first review the status of bioprinting. We then detail the fabrication process. Next we report on the testing of the graft in an in vivo animal model through electrophysiology and histology. This is followed by the introduction of a novel in vitro model, aimed at providing a fast, inexpensive and reliable method to test engineered nerve grafts. We describe our work on the optimization of the in vitro assay and then the testing of the graft using the optimized assay. We conclude with a summary of our accomplishments and make suggestions for some exciting future applications of our approach.