460307 Oligodendrocyte Survival, Proliferation, and Intracellular Redox State Is Dependent on 3D Hydrogel Mechanics
Here, we investigate how simply tuning the mechanical stiffness of a polyethylene glycol (PEG) based hydrogel affects the proliferation and intracellular redox state of two different oligodendrocyte precursor cell lines. PEG-dimethacrylate hydrogels with storage moduli from 230 to 1000 Pa were formed by tuning the concentration and molecular weight from 6% to 10% (wt/v) and 4600 to 8000 Da, respectively. When cells were encapsulated in the hydrogels, they proliferated in a stiffness dependent trend, where the largest increases in ATP and DNA concentrations were found in the most compliant hydrogel formulation. In gels with storage moduli of 230 Pa, the concentration of ATP was found to increase 12 fold over seven days while DNA increased 44% over seven days. To test the influence of antioxidants, we incorporated lactic acid into the hydrogel both as a soluble factor or into the polymer backbone where it can be released through hydrolytic degradation. As a measure of intracellular redox state, glutathione content within cells was measured in its reduced GSH form and in its oxidized GSSG disulfide form. Results from determining the ratio of reduced GSH to total glutathione (GSH and GSSG) suggest that incorporating lactic acid further reduces the intracellular redox state and increases cellular proliferation. These findings suggest the potential use of tunable PEG hydrogel systems to promote OPC growth, increase oligodendrocyte maturation, and repair the myelin sheath.