(114e) Polyethylene Glycol Microgel-Based Hydrogels for Neural Stem Cell Growth

Our goal, as a research team, is to understand how neural cells interact with their environment to design novel solutions that support nerve regeneration. Neural stem cells have the potential to give birth to new neurons through adulthood, yet little is known about niche microenvironment influences cellular response. As neural stem cells sense both the presence of bioactive signals and the mechanical properties of the extracellular matrix, microgel-based scaffolds are considered as a promising platform with the potential to decouple the mechanical and bioactive characterization of the microenvironment. We hypothesized that this platform could provide integrin-mediated adhesion to alter neural stem cell growth and differentiation through mechanotransduction. In this work, we developed hydrogel systems based on polyethylene glycol diacrylate (PEGDA) microgels generated via precipitation polymerization in an aqueous environment. First, 3 kDa PEGDA was synthesized with a 96% degree of acrylation based on H-NMR measurements. Then, it was combined with different ratios of acryl-PEG-amine to form functionalized microgels serving as building blocks for the hydrogels. These microgels will be characterized for morphology, size, and amine functionalization. Multiarmed PEG-NHS is then used in different concentrations to couple the microgels and modulate the stiffness of the formed scaffolds. The bioactive protein, laminin 511-E8 fragment, was used to promote stem cell adhesion through integrin α6β1. Neural stem cells were cultured on the scaffold to investigate their growth and differentiation and mechanotransduction was measured via YAP translocation. This study will help increase the understanding of complex molecular pathways, which in turn would help develop new tissue engineering alternatives.