Novel organ-on-chip microfluidic device based on hydraulically actuated hydrogel layers

Organs-on-chips (ooc) are small devices aiming to recapitulate the physiology and/or pathology of a living organism. Contrarily to commonly used flasks and dishes, ooc devices are designed to recapitulate the physico-chemical microenvironment of the cells. Thanks to these mimics of higher relevance, ooc devices are able to enhance cell differentiation compared to 2D culture techniques.

The field of ooc is still young, and many improvements remain to be done. For instance, one of the first organ-on-chip, produced by Huh et al. (2010), submitted epithelial and endothelial cells to mechanical stimuli by stretching a thin perforated PDMS membrane on which cells were attached. While extremely efficient, this setup presents several shortcomings, such as the high stiffness of PDMS compared to that of soft living tissues, and the poor relevance of a perforated membrane to study extravasation.

The HAHL (Hydraulically Actuated Hydrogel Layer) project relies on a soft biocompatible hydrogel to culture cells and submit them to mechanical stimuli. The use of a hydrogel enables cell culture both on its surface and within its bulk, mimicking a greater tissue complexity, including notably a “stromal compartment” in addition to the usual epithelium-endothelium dual culture. Relying on a pressure differential between each side of the hydrogel layer, the hydrogel can be stretched. Plus, hydraulic resistances can be used to control the flow. Thus, in the final setup, most physico-chemical parameters (stiffness, flow, strain, functionalization, etc.) are under the control of the operator to suit the desired organ and application at best.

The current goal of the project is to provide a proof of relevance, by reproducing Shigella infection on chip with a greater level of complexity than achieved before. More generally, the HAHL chip should be for interesting to investigate barrier tissue physiology and pathology (lung, gut, etc.).