Date of Award
Doctor of Philosophy
Comparative and Experimental Medicine
Mahdu Dhar, Stacey Stephenson, Alex Biris
Peripheral neuropathies are a debilitating problem in human and animal patients resulting in a diminished quality of life. The current gold standard methods for repair of critical size peripheral neuropathies have limitations that overall diminish the quality of life for patients. The use of nerve scaffolds composed of synthetic polymer-based materials to heal damaged nerves has become an attractive approach in regenerative medicine research. Studies have shown the biomaterial characteristics of graphene oxide to have potential in applications for regenerating damaged peripheral nerves. Studies have also shown that incorporating Mesenchymal Stem Cell (MSC) therapies into neural scaffold designs can significantly improve the quality of tissue healing as well. The hypothesis of this study is that a novel synthetic thin film composed of electro spun polycaprolactone (PCL) and modified with surface coating of Graphene Oxide (GO) and cultures of Human Mesenchymal Stem Cells (hMSC) will have the potential to regenerate a critical size peripheral nerve defect. The first objective studied the potential cytotoxic effect of graphene surfaces with different oxidative group saturation levels to adipose derived Rat MSC cultures. This objective also manufactured PCL materials of fibrous and smooth surface topographies using both electrospinning and polymer-drop techniques. The second objective assessed the in-vitro capabilities of High Oxygen Graphene (hGO) and GO surface modifications of both fibrous and smooth surface PCL material templates seeded with adipose derived hMSCs for materials effectiveness in supporting and guiding trans-differentiation of hMSC into a Schwann like cell lineage. The final objective involved the development of an approved critical nerve defect model in Rats to assess the in-vivo performance of electro-spun PCL films with GO surface modification and hMSC platform to stimulate nerve regeneration at a critical nerve defect. The degree of nerve regeneration was determined by exogenous detection of gait patterns in the rats during nerve repair and tissue identification/ measurements thru Histology sections. This study to date has shown that neural wraps composed of electro-spun PCL surface coated with GO can support the hMSC in both static and trans-differentiated forms and can stimulate nerve regeneration in a critical nerve defect rodent model.
Steiner, Richard, "Graphene-Based Nanomaterials in the Design of Nerve Conduits for Regenerative Medicine Applications. " PhD diss., University of Tennessee, 2019.