Glycopolymer Biomaterials for Regulating Adaptive Reprogramming in Glia

ABSTRACT Disruption of the central nervous system (CNS) by injury or neural device implantation results in glial cells deprioritizing neuronal support functions and undergoing an adaptive reprogramming. This adaptive reprogramming enables the acquisition of new functions by glial cells, allowing them to isolate and protect local, spared neural tissue. Chronically, isolation of spared neural tissue can be counterproductive, limiting neural regeneration and device integration. Therefore, it is critical to understand the mechanisms that regulate adaptive reprogramming and to develop tools to modulate the intensity and duration of the adaptive reprogramming response. I hypothesize that adaptive glial responses involve coordinated, multicellular, and temporally- regulated programs that are conserved across injury and foreign body contexts which can be altered by specific structural, mechanical, and surface chemistry properties of implanted biomaterials. To investigate this hypothesis, I will develop glycan-derived biomaterials to (1) test the ability of inherently bioactive glycans to stimulate glia-based repair following stroke, and (2) present unique chemical moieties and mechanical properties to establish and characterize synthetic glial interfaces. This work will contribute to the development of biomaterials for the CNS by creating a set of general principles that outline chemical motifs that can be used to direct glial responses, allowing for enhanced therapeutic outcomes following CNS injury and increased longevity of implanted neural devices.