Abstract

Lung-on-Chip Models of the Healthy and Diseased Lung Parenchyma

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

The complexity of the lung can be illustrated by its delicate tree-like architecture that ends with the alveolar sacs, where the gas exchanges take place. This whole environment is subjected to a cyclic, mechanical constraint induced by the respiratory movements. We recently reported about an advanced in-vitro model of the lung parenchyma that mimics the key aspects of the lung alveolar environment in an unprecedented way (Stucki et al., Lab Chip, 2015). The system reproduces the three-dimensional mechanical strain induced by the respiratory movements, the air-liquid interface and the ultra-thin barrier, using an elastic membrane made of a 3um thin PDMS porous (3um pores) layer on which cells can be cultured on both sides. We could demonstrate that the physiological mechanical stress significantly affects a number of barrier functions, such as the transport of molecules though the barrier. Furthermore, in view to make the system widely accessible, great care was taken to make it robust and simple to use. In contrast to the lung-on-chip reported by the Wyss Institute in Boston (Huh et al. Science 2010), our device mimics the three-dimensional movements induced by the respiration (instead of a unidirectional stress in the Wyss lung-on-chip). We also demonstrated that the three-dimensional breathing motions of the alveolar barrier can be monitored in real time with a micro-impedance tomography system (Mermoud et al., Sensors and Actuators B: 2018). The development of the lung-on-chip was awarded with a number of prizes, including the Venturekick awards, a nomination at the Swiss Medtech Award in 2017 and is currently under development at AlveoliX, a start-up aimed at bringing organs-on-chip on the market. Recently, we reported about another part of the lung alveolar barrier, the lung microvasculature.  Lung endothelial cells and lung pericytes seeded in a micro-engineered environment filled with fibrin gel, self-assemble to build a network of perfusable and contractile microvessels of only a few tens of micrometers in diameter (Bichsel et al., Tissue Eng. A, 2015). We could demonstrate for the first time in-vitro that microvessels contract upon exposure to a vasoconstrictor. This model, made of primary human cells of the lung is of great relevance for the investigation of pathomechanism of lung diseases.