Tissue-scale in vitro epithelial wrinkling and wrinkle-to-fold transition

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Although epithelial folding is commonly studied using in vivo animal models, such models exhibit critical limitations in terms of real-time observation and independent control of experimental parameters. Here, we develop a tissue-scale in vitro epithelial bilayer folding model that incorporates an epithelium and extracellular matrix (ECM) hydrogel, thereby emulating various folding structures found in in vivo epithelial tissue. Beyond mere folding, our in vitro model realizes a hierarchical transition in the epithelial bilayer, shifting from periodic wrinkles to a single deep fold under compression. Experimental and theoretical investigations of the in vitro model imply that both the strain-stiffening of epithelium and the poroelasticity of ECM influence the folded structures of epithelial tissue. The proposed in vitro model will aid in investigating the underlying mechanism of tissue-scale in vivo epithelial folding relevant to developmental biology and tissue engineering.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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