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Stress relaxation amplitude of hydrogels determines migration, proliferation, and morphology of cells in 3-D

Jonas Hazur, Nadine Endrizzi, Dirk W. Schubert, Aldo R. Boccaccini, View ORCID ProfileBen Fabry
doi: https://doi.org/10.1101/2021.07.08.451608
Jonas Hazur
aInstitute of Biomaterials, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
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Nadine Endrizzi
bDepartment of Physics, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
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Dirk W. Schubert
cInstitute for Polymer Materials, University of Erlangen-Nürnberg, Martensstraße 7, 91058, Erlangen, Germany
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Aldo R. Boccaccini
aInstitute of Biomaterials, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
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Ben Fabry
bDepartment of Physics, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
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  • ORCID record for Ben Fabry
  • For correspondence: ben.fabry@fau.de
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Abstract

The viscoelastic behavior of hydrogel matrices sensitively influences the cell behavior in 3D culture and biofabricated tissue model systems. Previous reports have demonstrated that cells tend to adhere, spread, migrate and proliferate better in hydrogels with pronounced stress relaxation. However, it is currently unknown if cells respond more sensitively to the amplitude of stress relaxation, or to the relaxation time constant. To test this, we compare the behavior of fibroblasts cultured for up to 10 days in alginate and oxidized alginate hydrogels with similar Young’s moduli but diverging stress relaxation behavior. We find that fibroblasts elongate, migrate and proliferate better in hydrogels that display a higher stress relaxation amplitude. By contrast, the cells’ response to the relaxation time constant was less pronounced and less consistent. Together, these data suggest that it is foremost the stress relaxation amplitude of the matrix that determines the ability of cells to locally penetrate and remodel the matrix, which subsequently leads to better spreading, faster migration, and higher cell proliferation. We conclude that the stress relaxation amplitude is a central design parameter for optimizing cell behavior in 3-D hydrogels.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 09, 2021.
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Stress relaxation amplitude of hydrogels determines migration, proliferation, and morphology of cells in 3-D
Jonas Hazur, Nadine Endrizzi, Dirk W. Schubert, Aldo R. Boccaccini, Ben Fabry
bioRxiv 2021.07.08.451608; doi: https://doi.org/10.1101/2021.07.08.451608
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Stress relaxation amplitude of hydrogels determines migration, proliferation, and morphology of cells in 3-D
Jonas Hazur, Nadine Endrizzi, Dirk W. Schubert, Aldo R. Boccaccini, Ben Fabry
bioRxiv 2021.07.08.451608; doi: https://doi.org/10.1101/2021.07.08.451608

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