A breathing lung-on-chip model of alveolar inflammation illustrating human drug response

June 30, 2023

Poster MPS Berlin 2023

Clémentine Richter1,2, Patrick Carius1,2, Daria Harig1,2, Nuria Roldan3, Janick Stucki3, Nina Hobi3, Tobias Krebs4, Brigitta Loretz1, Lorenz Latta1, Alberto Hidalgo1, Nicole Schneider-Daum1 and Claus-Michael Lehr1,2
1 Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany
2 Department of Pharmacy, Saarland University, Saarbrücken, Germany
3 AlveoliX AG, Swiss Organs-on-Chip Innovation, Bern, Switzerland
4 Vitrocell® Systems GmbH, Waldkirch, Germany

Macrophages, breathing dynamics and airliquid interface are key parameters when modelling alveoli and alveolar inflammation. This model is intended as complex and relevant model for inhaled anti-inflammatory drug efficacy testing.

The deep lung is characterized by a very large surface area (~140 m²), a high vascularization and a very thin epithelial barrier separating the blood stream from the inhaled air, including possible toxins and pathogens. This makes the deep lung a primary starting point for inflammatory and infectious diseases, but also for inhaled pharmaceutical agents. In this study, we established an inflamed alveolus model on a breathing lung-on-chip to mimic (patho-) physiological processes and predict human anti-inflammatory drug response. To reconstitute the air-blood-barrier in the lung-on-chip “AX12”a, we used the human alveolar epithelial cell line Arlob. To enhance the physiological relevance of the model, the importance of certain parameters was investigated, including the presence of alveolar macrophage surrogates as the main immune system component during early acute lung inflammation, the application of stretching of the epithelial cells to emulate the breathing motion in the alveoli, and the nebulization of anti-inflammatory treatment.

View Poster

News overview