Graphene Oxide and Mesenchymal Stem Cells for Nerve Tissue Engineering: Approaches in Functional Repair and Regeneration After Neural Injury

Neural injuries cause disruptions to the motor, sensory, and autonomic functions that significantly impact a person’s quality of life. Nerves have a limited ability to regenerate, and there are a lack of available treatments that restore the functional capabilities that are lost. Nerve tissue engineering and regenerative medicine offer a promising area of research for developing novel therapeutics to restore function through repair and regeneration after neural injury. Through five chapters, this dissertation investigates, develops, and evaluates novel therapeutics for functional nerve repair involving the components of graphene oxide (GO) and mesenchymal stem cells (MSCs). GO is a carbon-based nanomaterial whose physicochemical and electrical properties have shown promise influencing cell behavior for functional nerve repair; MSCs are multipotent cells derived from a variety of adult tissue sources which have shown promise as a supportive immunomodulator after injury. The first chapter explores these components, in addition to other biomaterials and cell types, that have been commonly used in nerve tissue engineering. The second chapter takes the components poly (lactic-co-glycolic acid) (PLGA) and GO to develop a novel nerve guidance conduit, seeded with MSCs, as a degradable, therapeutic implant for peripheral nerve injuries. We evaluate the biocompatibility and efficacy of the conduit in a sciatic nerve defect model for 6-months. The third chapter advances the cellular component of our therapeutic implant by developing neurospheres, a foundational 3D environment to be co-cultured with MSCs for enhanced functional repair. The fourth chapter aims to improve our understanding of how GO influences neurogenesis, which impacts the timing of implantation after injury. We also evaluate the material’s feasibility as an implant for penetrating traumatic brain injuries. The fifth chapter takes the PLGA and GO components and alters their chemistry for fabrication using resin-based printing. This allows for the expansion of applications from peripheral to central nervous system injuries. Overall, this dissertation improves our understanding of nerve tissue engineering, advances PLGA and GO as a therapeutic scaffold for peripheral and central nerve injuries, and advances MSCs to 3D multi-cellular spheroids, to improve functional repair and regeneration after neural injury.