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3D Hyaluronic Acid Hydrogels for Modeling Oligodendrocyte Progenitor Cell Behavior as a Function of Matrix Stiffness

View ORCID ProfileDeniz B. Unal, View ORCID ProfileSteven R. Caliari, View ORCID ProfileKyle J. Lampe
doi: https://doi.org/10.1101/2020.04.01.020412
Deniz B. Unal
1Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22903, United States
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Steven R. Caliari
1Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22903, United States
2Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22903, United States
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  • For correspondence: lampe@virginia.edu caliari@virginia.edu
Kyle J. Lampe
1Department of Chemical Engineering, University of Virginia, Charlottesville, Virginia 22903, United States
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  • For correspondence: lampe@virginia.edu caliari@virginia.edu
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Abstract

The lack of regenerative solutions for demyelination within the central nervous system (CNS) motivates the need for better understanding of the oligodendrocytes that give rise to myelination. In this work, we introduce a 3D hyaluronic acid (HA) hydrogel system to study the effects of mechanical properties on the behavior of oligodendrocyte progenitor cells (OPCs), the cells that differentiate into myelin-producing oligodendrocytes in the CNS. We tuned the stiffness of the hydrogels to match brain tissue (storage modulus 200 – 2000 Pa) and studied the effects of stiffness on metabolic activity, proliferation, and cell morphology of OPCs over a 7 day period. Although hydrogel mesh size decreased with increasing stiffness, all hydrogel groups facilitated OPC proliferation and mitochondrial metabolic activity to similar degrees. However, OPCs in the two lower stiffness hydrogel groups (169.8 ± 42.1 Pa and 793.9 ± 203.3 Pa) supported greater adenosine triphosphate (ATP) levels per cell than the highest stiffness hydrogels (2178.7 ± 127.2 Pa). Lower stiffness hydrogels also supported higher levels of cell viability and larger cell spheroid formation compared to the highest stiffness hydrogels. Together, these data suggest that 3D HA hydrogels are a useful platform for studying OPC behavior and that OPC growth/metabolic health may be favored in lower stiffness microenvironments mimicking brain tissue mechanics.

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Posted April 02, 2020.
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3D Hyaluronic Acid Hydrogels for Modeling Oligodendrocyte Progenitor Cell Behavior as a Function of Matrix Stiffness
Deniz B. Unal, Steven R. Caliari, Kyle J. Lampe
bioRxiv 2020.04.01.020412; doi: https://doi.org/10.1101/2020.04.01.020412
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3D Hyaluronic Acid Hydrogels for Modeling Oligodendrocyte Progenitor Cell Behavior as a Function of Matrix Stiffness
Deniz B. Unal, Steven R. Caliari, Kyle J. Lampe
bioRxiv 2020.04.01.020412; doi: https://doi.org/10.1101/2020.04.01.020412

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