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. 2019 Apr 3;10:1496. doi: 10.1038/s41467-019-09331-6

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 8 — Consistency of overall results from the multiple experimental model systems under study. Epithelial cells (re)populating collagenase-softened (treated) substrates expressed significantly higher levels of limbal markers and lower levels of differentiation and active mechanotransduction markers compared to the untreated (control) tissues, independently of the system’s degree of complexity (i.e., topography, biochemical composition). In addition, the maintenance of limbal cell morphology and failure to elicit major pro-inflammatory responses after tissue softening were similarly observed for all in vitro, ex vivo, and in vivo experiments. The comparable results obtained on both simple and complex substrates supported the notion that the cellular effects were derived from the modulation of tissue biomechanics, and not due to tissue topography or composition (i.e., exposure to cryptic biochemical cues or growth factors)