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Response of neuroglia to hypoxia-induced oxidative stress using enzymatically crosslinked hydrogels

Abstract

Three-dimensional cultures have exciting potential to mimic aspects of healthy and diseased brain tissue to examine the role of physiological conditions on neural biomarkers, as well as disease onset and progression. Hypoxia is associated with oxidative stress, mitochondrial damage, and inflammation, key processes potentially involved in Alzheimer’s and multiple sclerosis. We describe the use of an enzymatically-crosslinkable gelatin hydrogel system within a microfluidic device to explore the effects of hypoxia-induced oxidative stress on rat neuroglia, human astrocyte reactivity, and myelin production. This versatile platform offers new possibilities for drug discovery and modeling disease progression.

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Acknowledgments

The authors acknowledge Dr. Austin Cyphersmith (IGB, University of Illinois) for the assistance with fluorescence imaging, Mai Ngo for the assistance with microfluidic chips, and Zona Hrnjak and Aidan Gilchrist for the compression testing methodology and the custom MATLAB code for modulus analysis. The authors gratefully acknowledge support from the Scott H. Fisher IGB Graduate Student Research Fund. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health (NIH) under Award Number R01 CA197488, the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number R01 DK099528, as well as the Chemical Transformations Initiative at Pacific Northwest National Laboratory (PNNL) under the Laboratory Directed Research and Development Program at PNNL, a multiprogram national laboratory operated by Battelle for the U.S. Department of Energy (DOE). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the DOE. The authors are also grateful for additional funding provided by the Department of Chemical & Biomolecular Engineering and the Carl R. Woese Institute for Genomic Biology at the University of Illinois at Urbana-Champaign.

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Correspondence to Sara Pedron.

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These authors contributed equally to this work.

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Zambutot, S.G., Serranot, J.F., Vilbert, A.C. et al. Response of neuroglia to hypoxia-induced oxidative stress using enzymatically crosslinked hydrogels. MRS Communications 10, 83–90 (2020). https://doi.org/10.1557/mrc.2019.159

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