Engineered Tissue Folding by Mechanical Compaction of the Mesenchyme

Publication date: Available online 28 December 2017
Source:Developmental Cell
Author(s): Alex J. Hughes, Hikaru Miyazaki, Maxwell C. Coyle, Jesse Zhang, Matthew T. Laurie, Daniel Chu, Zuzana Vavrušová, Richard A. Schneider, Ophir D. Klein, Zev J. Gartner
Many tissues fold into complex shapes during development. Controlling this process in vitro would represent an important advance for tissue engineering. We use embryonic tissue explants, finite element modeling, and 3D cell-patterning techniques to show that mechanical compaction of the extracellular matrix during mesenchymal condensation is sufficient to drive tissue folding along programmed trajectories. The process requires cell contractility, generates strains at tissue interfaces, and causes patterns of collagen alignment around and between condensates. Aligned collagen fibers support elevated tensions that promote the folding of interfaces along paths that can be predicted by modeling. We demonstrate the robustness and versatility of this strategy for sculpting tissue interfaces by directing the morphogenesis of a variety of folded tissue forms from patterns of mesenchymal condensates. These studies provide insight into the active mechanical properties of the embryonic mesenchyme and establish engineering strategies for more robustly directing tissue morphogenesis ex vivo.

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Teaser

A key challenge for tissue engineering is to harness the organizational principles that generate complex tissue topography in vivo. Hughes et al. find that mesenchymal compaction processes are sufficient to generate curvature at tissue interfaces and develop a framework to engineer curvature trajectories of reconstituted tissues via patterns of mesenchymal condensates.


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