Abstract

Lung-on-Chip Models for Drug Discovery Applications

Olivier Guenat, Head, Organs-on-Chip Technologies, ARTORG Center for Biomedical Engineering Research, University of Bern-Switzerland

Commercially available in vitro models of the lung poorly represent the complex architecture and the dynamic environment of the air-blood barrier. Here we present two lung-on-chip models that mimic a number of aspects found in this particular environment. The first lung-on-chip model reproduces the thin alveolar barrier and the cyclic movements induced by the respiration. Results obtained with lung epithelial and endothelial cells demonstrate that a physiological mechanical strain significantly affects the cells response.  In addition to the capabilities of this in vitro model to mimic the in vivo response, this lung-on-chip model is designed to be robust and comprise an array of three wells in view to its further implementation as a drug discovery tool. A second model reproduces the lung microvasculature. It is made of endothelial and primary pericytes from patients that self-assemble in a microfluidic construct filled with fibrin gel in a tight, stable and perfusable microvessels network. The role of the pericytes revealed to be crucial to the stability and tightness of the microvessels. In addition, their presence enabled to restore one of the key functions of those capillaries: their vasoconstriction. Such organs-on-chip systems have the potential to be used to screen new molecules for their efficacy in a very near future.