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A lung-on-a-chip array with an integrated bio-inspired respiration mechanism

Significance statement

The drug discovery process is hampered by an extremely poor successful rate (only about 10%) and tremendous costs. The reasons of this dramatic failure rate are drug toxicity and inefficacy issues that are not identified early on by standard in-vitro and in-vivo models. The lung-on-a-chip presented in this article, which mimics in an unprecedented way the biophysical microenvironment of the air-blood barrier, is expected to better predict the effects of respiratory drug candidates in humans and thus reduce the costs of clinical trials. As an example, we show that the permeability of the air-blood barrier is significantly affected by the mechanical strain induced by the breathing movements. The concentration of inhaled particles (from pollution, aerosols or inhalation drugs) that enters in the blood stream via the lung barrier therefore importantly depends on this dynamic environment. Another important aspect that was tested with this lung-on-chip for the first time, is the use of primary healthy lung alveolar cells from patients who underwent a lung resection. These primary cells behaved differently in a physiological dynamic environment vs. a static environment. This is a major step in view of personalised medicine assays carried out in in-vivo-like conditions.

A lung-on-a-chip array with an integrated bio-inspired respiration mechanism. Global Medical Discovery

 

 

 

 

 

 

 

 

 

Journal Reference

Stucki AO, Stucki JD, Hall SR, Felder M, Mermoud Y, Schmid RA, Geiser T, Guenat OT. Lab Chip. 2015 Mar 7;15(5):1302-10.

ARTORG Center for Biomedical Engineering Research, Lung Regeneration Technologies, University of Berne, Switzerland.

Email: [email protected]

Abstract

We report a lung-on-a-chip array that mimics the pulmonary parenchymal environment, including the thin alveolar barrier and the three-dimensional cyclic strain induced by breathing movements. The micro-diaphragm used to stretch the alveolar barrier is inspired by the in vivo diaphragm, the main muscle responsible for inspiration. The design of this device aims not only at best reproducing the in vivo conditions found in the lung parenchyma but also at making the device robust and its handling easy. An innovative concept, based on the reversible bonding of the device, is presented that enables accurate control of the concentration of cells cultured on the membrane by easily accessing both sides of the membranes. The functionality of the alveolar barrier could be restored by co-culturing epithelial and endothelial cells that form tight monolayers on each side of a thin, porous and stretchable membrane. We showed that cyclic stretch significantly affects the permeability properties of epithelial cell layers. Furthermore, we also demonstrated that the strain influences the metabolic activity and the cytokine secretion of primary human pulmonary alveolar epithelial cells obtained from patients. These results demonstrate the potential of this device and confirm the importance of the mechanical strain induced by breathing in pulmonary research.

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