Exploring The Regenerative Response To Peripheral Nervous System Injury PDF Download

Damage to tissues in the central nervous system (CNS) and peripheral nervous system (PNS) is of serious concern since they possess a limited capacity to regenerate. A new generation of interventions centered on the essential element magnesium (Mg) offers a promising proposition to improve treatment options for nervous tissue trauma. The long-term goal of our research is to understand how ionic and metallic Mg can be used to therapeutically interact with CNS and PNS tissues. Initial experiments focused on studying the interaction between Mg ion (Mg2+) solutions and CNS-derived neural stem/progenitor cells (NSCs) in vitro. Latter studies focused on using Mg metal as a novel biomaterial in peripheral nerve tissue engineering. The use of Mg2+ solutions to treat traumatic brain injury (TBI) and stroke is well documented and shows tremendous promise in animal models; however, there are still obstacles to translating these findings into effective treatments for humans. When administered systemically, Mg2+ can attenuate a host of complex, harmful biochemical cascades that occur in CNS tissue in the hours and days after injury, though the exact mechanisms are still unclear. With this in mind, we sought to develop a culture system that would be responsive to changes in Mg2+ in an effort to better understand the interactions between Mg2+ and CNS tissue (NSCs). The central hypothesis of this work was that neural cells (NSCs) would show altered biological responses, including beneficial effects, to moderately elevated Mg2+ concentrations in vitro. Severe injuries to the PNS are also resistant to current treatment methods. There is a great clinical need for an engineered alternative to autografts, the current standard of treatment for nerve defects greater than 3cm. It has been hypothesized that nerve conduits are ineffective at bridging defects greater than 3cm because of inadequate mechanical support for tissue regeneration in the conduit lumen. We proposed that metallic Mg, which has been shown to be biocompatible and biodegradable in orthopedic and vascular applications, could serve as a physical support, a scaffold, within a nerve conduit. The central hypothesis of this work was that metallic Mg, placed in the lumen of a nerve conduit, would improve nerve regeneration by serving as a scaffold that would safely resorb into the body after mechanical support was no longer required by regenerating tissue. The results from the research in this dissertation identify a culture system for studying Mg2+ supplementation using primary CNS-derived stem cells and present a novel use for metallic Mg as a biodegradable scaffold in PN tissue engineering. New methods for monitoring neural cell health in vitro are described, as are methods for monitoring the response of nerve tissue in the presence of Mg metal and the resorption of Mg metal surrounded by nerve tissue in situ. The findings of this research will contribute toward the development of more sophisticated culture systems for studying the interaction between neural cells and Mg2+ and also toward the further development of biodegradable metals as tissue engineering scaffolds for the improvement of PN tissue repair.