한빛사논문
Mark J. Mondrinos1,*, Farid Alisafaei2, Alex Y. Yi1, Hossein Ahmadzadeh2, Insu Lee3, Cassidy Blundell1, Jeongyun Seo1, Matthew Osborn1, Tae-Joon Jeon4, Sun Min Kim3, Vivek B. Shenoy2,5 and Dongeun Huh1,5,6,†
1Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
2Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
3Department of Mechanical Engineering, Inha University, Incheon, Korea.
4Department of Biological Engineering, Inha University, Incheon, Korea.
5NSF Science and Technology Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
6Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
†Corresponding author.
*Present address: Department of Biomedical Engineering, Tulane University, New Orleans, LA 70118, USA.
Abstract
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.
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