Programmable Tissue Folding Patterns in Structured Hydrogels

Folding of mucosal tissues, such as within the epithelium of the upper respiratory airways, is critical for organ function. Studying the influence of folded tissue patterns on cellular function is challenging mainly due to the lack of suitable cell culture platforms that can recreate dynamic tissue folding in vitro. Here, we describe a bilayer hydrogel folding system composed of alginate/polyacrylamide double network (DN) and hyaluronic acid (HA) hydrogels to generate static folding patterns based on mechanical instabilities. By encapsulating human fibroblasts into patterned HA hydrogels, human bronchial epithelial cells formed a folded pseudostratified monolayer. Using micromagnetic particles, DN hydrogels reversibly folded into pre-defined patterns and enabled programmable on-demand folding of cell-laden hydrogel systems upon applying a magnetic field. This hydrogel construct provides a dynamic culture system for mimicking tissue folding in vitro, which is extendable to other cell types and organ systems. This article is protected by copyright. All rights reserved