Surface-directed engineering of tissue anisotropy in microphysiological models of musculoskeletal tissue

Mark J. Mondrinos, Farid Alisafaei, Alex Y. Yi, Hossein Ahmadzadeh, Insu Lee, Cassidy Blundell, Jeongyun Seo, Matthew Osborn, Tae Joon Jeon, Sun Min Kim, Vivek B. Shenoy, Dongeun Huh

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


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.

Original languageEnglish (US)
Article numbereabe9446
JournalScience Advances
Issue number11
StatePublished - Mar 12 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General


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