European Respiratory Journal

Yara-Maria Proust, Nuria Roldan, Nicole Schneider-Daum, Claus Michael-Lehr, Hanno Huwer, Tobias Krebs, Olivier T. Guenat, Janick D. Stucki, Nina Hobi


The widespread application of nanoparticles has drawn intense concerns about their impact on the environment and human health. The major route of nanoparticles into the human body are the alveolar ducts, leading possibly to adverse effects on the epithelial cells, covering and protecting these lung cavities. Therefore, it is of great interest to evaluate potential risks of nanoparticles on the alveolar epithelial cells under physiological conditions. Here, we introduce the first breathing human alveolar-on-chip model allowing simultaneous exposure of 12 alveolar barriers to liquid aerosols. 

Human primary alveolar epithelial cells were cultured on chip. As a first step, the adaptation of the cells to air-liquid interface (ALI) and stretch conditions was tested. For that, cells were cultured for 7 days in static conditions until reaching confluency and tightness, before applying cyclic 3D stretch and ALI. After 14 days, the toxicological effect of ZnO was investigated by liquid and aerosol exposure on stretched and non-stretched cells. Cell integrity and inflammation status were assessed by TEER, cell viability and cytokine response at different timepoints. 

Results demonstrate that on-chip culturing, applying stretch and ALI conditions, stimulate cell viability and in-vivo like differentiation. Furthermore, we could show that ZnO nanotoxicity was drastically enhanced in stretched cells. These results propose the alveolar-on-chip exposure model as valuable tool for drug and molecules safety studies. Further studies using different nanoparticles are needed to strengthen our hypothesis.