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Surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue
Here, we present an approach to model and adapt the mechanical regulation of morphogenesis that uses contractile cells as sculptors of engineered tissue anisotropy in vitro. Our method uses heterobifunctional cross-linkers to create mechanical boundary constraints that guide surface-directed sculpti...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954445/ https://www.ncbi.nlm.nih.gov/pubmed/33712463 http://dx.doi.org/10.1126/sciadv.abe9446 |
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author | Mondrinos, Mark J. Alisafaei, Farid Yi, Alex Y. Ahmadzadeh, Hossein Lee, Insu Blundell, Cassidy Seo, Jeongyun Osborn, Matthew Jeon, Tae-Joon Kim, Sun Min Shenoy, Vivek B. Huh, Dongeun |
author_facet | Mondrinos, Mark J. Alisafaei, Farid Yi, Alex Y. Ahmadzadeh, Hossein Lee, Insu Blundell, Cassidy Seo, Jeongyun Osborn, Matthew Jeon, Tae-Joon Kim, Sun Min Shenoy, Vivek B. Huh, Dongeun |
author_sort | Mondrinos, Mark J. |
collection | PubMed |
description | Here, we present an approach to model and adapt the mechanical regulation of morphogenesis that uses contractile cells as sculptors of engineered tissue anisotropy in vitro. Our method uses heterobifunctional cross-linkers to create mechanical boundary constraints that guide surface-directed sculpting of cell-laden extracellular matrix hydrogel constructs. Using this approach, we engineered linearly aligned tissues with structural and mechanical anisotropy. A multiscale in silico model of the sculpting process was developed to reveal that cell contractility increases as a function of principal stress polarization in anisotropic tissues. We also show that the anisotropic biophysical microenvironment of linearly aligned tissues potentiates soluble factor-mediated tenogenic and myogenic differentiation of mesenchymal stem cells. The application of our method is demonstrated by (i) skeletal muscle arrays to screen therapeutic modulators of acute oxidative injury and (ii) a 3D microphysiological model of lung cancer cachexia to study inflammatory and oxidative muscle injury induced by tumor-derived signals. |
format | Online Article Text |
id | pubmed-7954445 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-79544452021-03-24 Surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue Mondrinos, Mark J. Alisafaei, Farid Yi, Alex Y. Ahmadzadeh, Hossein Lee, Insu Blundell, Cassidy Seo, Jeongyun Osborn, Matthew Jeon, Tae-Joon Kim, Sun Min Shenoy, Vivek B. Huh, Dongeun Sci Adv Research Articles Here, we present an approach to model and adapt the mechanical regulation of morphogenesis that uses contractile cells as sculptors of engineered tissue anisotropy in vitro. Our method uses heterobifunctional cross-linkers to create mechanical boundary constraints that guide surface-directed sculpting of cell-laden extracellular matrix hydrogel constructs. Using this approach, we engineered linearly aligned tissues with structural and mechanical anisotropy. A multiscale in silico model of the sculpting process was developed to reveal that cell contractility increases as a function of principal stress polarization in anisotropic tissues. We also show that the anisotropic biophysical microenvironment of linearly aligned tissues potentiates soluble factor-mediated tenogenic and myogenic differentiation of mesenchymal stem cells. The application of our method is demonstrated by (i) skeletal muscle arrays to screen therapeutic modulators of acute oxidative injury and (ii) a 3D microphysiological model of lung cancer cachexia to study inflammatory and oxidative muscle injury induced by tumor-derived signals. American Association for the Advancement of Science 2021-03-12 /pmc/articles/PMC7954445/ /pubmed/33712463 http://dx.doi.org/10.1126/sciadv.abe9446 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Mondrinos, Mark J. Alisafaei, Farid Yi, Alex Y. Ahmadzadeh, Hossein Lee, Insu Blundell, Cassidy Seo, Jeongyun Osborn, Matthew Jeon, Tae-Joon Kim, Sun Min Shenoy, Vivek B. Huh, Dongeun Surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue |
title | Surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue |
title_full | Surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue |
title_fullStr | Surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue |
title_full_unstemmed | Surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue |
title_short | Surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue |
title_sort | surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954445/ https://www.ncbi.nlm.nih.gov/pubmed/33712463 http://dx.doi.org/10.1126/sciadv.abe9446 |
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