Controlling the fate of stem cells through two-and three-dimensional scaffolds based on bioresorbable polymers and graphenen derivativesa study towards nerve tissue regeneration

Abstract

Neurological disorders are the major cause of long-term impairment and the second largest cause of death worldwide. Hence, there is an urgent need for new treatments that allow the functional recovery of damaged tissue. Among the experimental treatments, bioresorbable polyesters are showing great results in preclinical and clinical trials due to their biocompatibility, tunable degradability, versatility and physicochemical and mechanical properties. In this PhD thesis nanostructured scaffolds based on bioresorbable polymers and graphene oxide were developed to study the attachment, aligned growth and migration of both murine and human stem cells, avoiding the use of extracellular matrix-like compounds coatings. The use of murine neural stem cells allowed to study the differentiation pattern of the cells over the nanostructuredscaffolds, focusing on the achievement of a balanced neuronal and glial support, for a long-term survival of the cultures in vitro. The use of a relatively new source of stem cells, now considered clinical waste, like the dental pulp stem cells, allowed to minimize the ethical concerns and provide an actual alternative for personalized medicine in future therapies. To test this alternative, the regeneration capabilities of the nanostructured scaffolds were studied after the impairment of the rostral migratory stream in a rodent model in vivo. And with the aim of addressing the enhanced restoration capabilities of the personalized advanced medical products combining polymeric materials and human stem cells, the regeneration of the rostral migratory stream was compared when grafting the dental pulp stem cells, alone or in combination with our nanostructured scaffolds.Finally, to better resemble the neural niche in vitro graphene derivatives-based three-dimensional scaffolds with tunable geometry, mechanical and electrical conductive features were fabricated and their effect studied on cell survival and differentiation. Afterward, cerium oxide nanoparticles were incorporated to provide enhanced antioxidant and neuroprotective features and their effect on the establishment of balanced neuronal and glial co-cultures studied.Overall, this thesis gives new insights into the design of polymeric materials based on graphene derivatives for future personalized advanced medical products in combination with human stem cells for the restoration of the nervous system.