Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
Proc Natl Acad Sci U S A. 2018 Jul 17;115(29):7503-7508. doi: 10.1073/pnas.1802361115. Epub 2018 Jul 2.
The surfaces of many hollow or tubular tissues/organs in our respiratory, gastrointestinal, and urogenital tracts are covered by mucosa with folded patterns. The patterns are induced by mechanical instability of the mucosa under compression due to constrained growth. Recapitulating this folding process in vitro will facilitate the understanding and engineering of mucosa in various tissues/organs. However, scant attention has been paid to address the challenge of reproducing mucosal folding. Here we mimic the mucosal folding process using a cell-laden hydrogel film attached to a prestretched tough-hydrogel substrate. The cell-laden hydrogel constitutes a human epithelial cell lining on stromal component to recapitulate the physiological feature of a mucosa. Relaxation of the prestretched tough-hydrogel substrate applies compressive strains on the cell-laden hydrogel film, which undergoes mechanical instability and evolves into morphological patterns. We predict the conditions for mucosal folding as well as the morphology of and strain in the folded artificial mucosa using a combination of theory and simulation. The work not only provides a simple method to fold artificial mucosa but also demonstrates a paradigm in tissue engineering via harnessing mechanical instabilities guided by quantitative mechanics models.
我们的呼吸、胃肠道和泌尿生殖道中的许多中空或管状组织/器官的表面都覆盖着具有折叠图案的黏膜。这些图案是由黏膜在受限生长下受压时的机械不稳定性引起的。在体外再现这种折叠过程将有助于理解和工程化各种组织/器官中的黏膜。然而，人们很少关注解决黏膜折叠的挑战。在这里，我们使用附着在预拉伸坚韧水凝胶基底上的细胞负载水凝胶膜来模拟黏膜折叠过程。细胞负载水凝胶构成了基质上的人上皮细胞衬里，以再现黏膜的生理特征。预拉伸坚韧水凝胶基底的松弛对细胞负载水凝胶膜施加压缩应变，使细胞负载水凝胶膜发生机械不稳定性并演变成形态图案。我们使用理论和模拟的组合来预测黏膜折叠的条件以及折叠人工黏膜的形态和应变。这项工作不仅提供了一种简单的折叠人工黏膜的方法，而且通过利用定量力学模型指导的机械不稳定性，为组织工程提供了一个范例。
