Folding artificial mucosa with cell-laden hydrogels guided by mechanics models

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 proc...

Full description

Bibliographic Details
Main Authors: Meng, Hu, Leong, Kam W., Chan, Hon Fai, Zhao, Ruike, Parada Hernandez, German Alberto, Griffith, Linda G, Zhao, Xuanhe
Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering
Format: Article
Published: National Academy of Sciences (U.S.) 2019
Online Access:http://hdl.handle.net/1721.1/120544
https://orcid.org/0000-0002-9292-5267
https://orcid.org/0000-0001-7922-0249
https://orcid.org/0000-0002-1801-5548
https://orcid.org/0000-0001-5387-6186
Description
Summary: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. Keywords: mucosa; hydrogel; mechanical instabiity; tissue engineering; biomechanics