Abstract

A Bioinspired Lung Alveoli Model with Physiological Relevance for Drug Discovery Research

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

The high attrition rate and the huge costs related to the drug development process have recently led to the emergence of advanced in-vitro models that better reproduce the cellular and biophysical/-chemical environment found in-vivo. In contrast to standard in-vitro systems, these models, called organs-on-chip, are expected to better predict drugs’s response in humans and are thus widely seen as having the potential to revolutionize the way drug discovery is made. The objectives of the ARTORG Lung Regeneration Technologies Lab are the development of advanced in-vitro models able to mimic specific parameters of the environment of healthy or diseased lungs. These systems, based on microfluidics, are aimed at better understanding the pathophysiology and –mechanism of specific respiratory diseases. One of the research directions under investigation in the lab focuses on the reproduction of a healthy and diseased (lung fibrosis) lung alveolar environment. A bioinspired microfluidic chip mimicking the air-blood barrier was developed that reproduces the cyclic mechanical strain induced by the respiration. Permeability assays performed with bronchial cell line revealed the effect of the mechanical strain as well as the size of the molecules studied. In a second set of experiment, primary epithelial cells from patients undergoing partial lung resection were exposed to cyclic stretch during 24h. The effect of the stretch was clearly demonstrated on those cells with a clear increase of inflammation marker IL-8 compared to the cells were cultured in a static mode. Finally, a model aimed at reproducing the alveolar epithelial microinjuries that are typical to pulmonary fibrosis will be shown.