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Article

Modulation of Cell-Cycle Progression by Hydrogen Peroxide-Mediated Cross-Linking and Degradation of Cell-Adhesive Hydrogels

Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, Toyonaka 560-8531, Osaka, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Rustem E. Uzbekov, Claude Prigent and Ludger Hengst
Cells 2022, 11(5), 881; https://doi.org/10.3390/cells11050881
Received: 13 January 2022 / Revised: 24 February 2022 / Accepted: 1 March 2022 / Published: 3 March 2022
(This article belongs to the Special Issue The Regulation of the Cell Cycle)
The cell cycle is known to be regulated by features such as the mechanical properties of the surrounding environment and interaction of cells with the adhering substrates. Here, we investigated the possibility of regulating cell-cycle progression of the cells on gelatin/hyaluronic acid composite hydrogels obtained through hydrogen peroxide (H2O2)-mediated cross-linking and degradation of the polymers by varying the exposure time to H2O2 contained in the air. The stiffness of the hydrogel varied with the exposure time. Human cervical cancer cells (HeLa) and mouse mammary gland epithelial cells (NMuMG) expressing cell-cycle reporter Fucci2 showed the exposure-time-dependent different cell-cycle progressions on the hydrogels. Although HeLa/Fucci2 cells cultured on the soft hydrogel (Young’s modulus: 0.20 and 0.40 kPa) obtained through 15 min and 120 min of the H2O2 exposure showed a G2/M-phase arrest, NMuMG cells showed a G1-phase arrest. Additionally, the cell-cycle progression of NMuMG cells was not only governed by the hydrogel stiffness, but also by the low-molecular-weight HA resulting from H2O2-mediated degradation. These results indicate that H2O2-mediated cross-linking and degradation of gelatin/hyaluronic acid composite hydrogel could be used to control the cell adhesion and cell-cycle progression. View Full-Text
Keywords: gelatin; hyaluronic acid; Fucci2; horseradish peroxidase; degradation gelatin; hyaluronic acid; Fucci2; horseradish peroxidase; degradation
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MDPI and ACS Style

Mubarok, W.; Elvitigala, K.C.M.L.; Nakahata, M.; Kojima, M.; Sakai, S. Modulation of Cell-Cycle Progression by Hydrogen Peroxide-Mediated Cross-Linking and Degradation of Cell-Adhesive Hydrogels. Cells 2022, 11, 881. https://doi.org/10.3390/cells11050881

AMA Style

Mubarok W, Elvitigala KCML, Nakahata M, Kojima M, Sakai S. Modulation of Cell-Cycle Progression by Hydrogen Peroxide-Mediated Cross-Linking and Degradation of Cell-Adhesive Hydrogels. Cells. 2022; 11(5):881. https://doi.org/10.3390/cells11050881

Chicago/Turabian Style

Mubarok, Wildan, Kelum Chamara Manoj Lakmal Elvitigala, Masaki Nakahata, Masaru Kojima, and Shinji Sakai. 2022. "Modulation of Cell-Cycle Progression by Hydrogen Peroxide-Mediated Cross-Linking and Degradation of Cell-Adhesive Hydrogels" Cells 11, no. 5: 881. https://doi.org/10.3390/cells11050881

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