An Integrated Study Towards Curing Neurodegenerative Disorders Using Materials Science And Stem Cell-Based Tissue Engineering Approaches

Neurodegenerative diseases affect around one billion people globally that are characterized by irreversible degeneration of brain tissues. These diseases cause serious effects on patients degrading their brain functions and causing enormous physical and mental health issues. Parkinson\u27s disease (PD) is one of the most common neurodegenerative disorder affecting millions of people worldwide which results from loss of dopaminergic (DA) neurons in the mid-brain. Unfortunately, no medical treatment is effective to date for these significant brain disorders, except some symptomatic therapies only focusing on improving the quality of patient\u27s life. Two current approaches hold great promise in targeting PD as well as other neurodegenerative diseases, by surgically implanting electrodes for deep brain stimulation (DBS) and transplanting healthy neuronal cells at the site of tissue loss, due to disease in the brain. However, cells for transplantation need to be delivered via a scaffold. Nerve regeneration in a scaffold of appropriate biomaterial is of great importance while being implanted inside the animal body for further clinical applications. In this Dissertation, both approaches for treating PD were incorporated by in vitro studies using surface-engineering and tissue-engineering techniques. For the first approach, graphene oxide (GO) coatings on commercially available 316L stainless steel (SS) surfaces was done to reduce the neurotoxicity of SS and modified surfaces showed hydrophilicity, biocompatibility, cell proliferation, and decreased reactive oxygen species (ROS) expression with SHSY-5Y neuroblastoma cell lines. Transplantation of stem cells in vivo is another approach for reducing the progression of PD by reversing the loss of affected DA neurons. So, our second approach included differentiation of mesenchymal stem cells into DA neurons using Sonic hedgehog, Fibroblast growth factor, Basic fibroblast growth factor and Brain-derived neurotrophic factor, while they were cultured within collagen coated three-dimensional (3D) Graphene foams. 3D multilayer graphene scaffold could mimic the actual brain tissue environment and more closely exhibit morphologies, functions and other necessary characteristics compared to 2D culture on tissue culture plastic. The graphene-based scaffolds were not cytotoxic as cells seemed to retain viability and proliferated substantially during in vitro culture. These results suggest the utility of Graphene-based materials towards neuronal and stem cell culture, which is an important step for neural tissue engineering applications