Abstract

Healthy and Diseased Lung-on-Chip Models For Preclinical Applications

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

Organs-on-chip are widely seen as being the next generation of in-vitro models. In contrast to standard models based on Petri dish technology, they allow in an unprecedented way to reproduce the cellular environment found in-vivo. A further benefit of these systems is the small amount of cells required to perform a cell-based assay. This is an important condition when scarce patients’ material is tested. The micro-engineered environment enables the cells to maintain their original functions. This enables the creation of in-vitro models with higher drugs’ response prediction capability in humans. However, prior to seeing organs-on-chip integrated in preclinical routine assays, requirements such as robustness, reliability and simplicity of use need equally to be met. We report on lung alveolar models that accurately mimic the physiological or the pathophysiological lung parenchyma situation. Furthermore they are designed in a robust way that guarantees a high reliability and ease of use. A first system reproduces the environment of the alveolar barrier, including an ultra-thin, porous and flexible membrane and the three-dimensional cyclic mechanical strain of the breathing motions. Primary cells from patients cultured at the air-liquid interface and exposed to a physiological cyclic mechanical stress are shown to preserve their typical alveolar epithelial phenotype and their barrier function. With a second system, an acute lung injury model is presented, which demonstrates the effect of the physiological, mechanical stress on the lung endothelial cells exposed to bacterial infection. In view to making this system compatible with a preclinical setting an array of 12 individual lung-on-chips was developed and integrated in a multi-well plate. The system is compatible with standard equipment used in a cell biology laboratory, such as a plate reader, microscopes and multi-pipette robots.