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Front. Bioeng. Biotechnol. | doi: 10.3389/fbioe.2019.00003

Impaired Wound Healing of Alveolar Lung Epithelial Cells in a Breathing Lung-on-a-chip

Marcel Felder1, Bettina S. Trüeb1,  Andreas O. Stucki1, Sarah Borcard1, 2, Janick D. Stucki1, 3,  Bruno Schnyder2, Thomas Geiser4 and  Olivier Guenat1, 3, 4, 5*
  • 1ARTORG Center for Biomedical Engineering, University of Bern, Switzerland
  • 2Institute of Life Technologies, University of Applied Sciences and Arts of Western Switzerland, Switzerland
  • 3AlveoliX AG, Switzerland
  • 4Universitätsklinik für Pneumologie, Inselspital, Switzerland
  • 5Universitätsklinik für Thoraxchirurgie, Inselspital, Switzerland

The lung alveolar region experiences remodeling during several acute and chronic lung diseases, as for instance idiopathic pulmonary fibrosis (IPF), a fatal disease, whose onset is correlated with repetitive microinjuries to the lung alveolar epithelium and abnormal alveolar wound repair. Although a high degree of mechanical stress (>20% linear strain) is thought to induce IPF, the effect of lower, physiological levels of strain (5–12% linear strain) on IPF pathophysiology remains unknown. In this study, we examined the influence of mechanical strain on alveolar epithelial wound healing. For this purpose, we adopted the “organ-on-a-chip” approach, which provides the possibility of reproducing unique aspects of the in vivo cellular microenvironment, in particular its dynamic nature. Our results provide the first demonstration that a wound-healing assay can be performed on a breathing lung-on-a-chip equipped with an ultra-thin elastic membrane. We cultured lung alveolar epithelial cells to confluence, the cells were starved for 24 h, and then wounded by scratching with a standard micropipette tip. Wound healing was assessed after 24 h under different concentrations of recombinant human hepatic growth factor (rhHGF) and the application of cyclic mechanical stretch. Physiological cyclic mechanical stretch (10% linear strain, 0.2 Hz) significantly impaired the alveolar epithelial wound-healing process relative to culture in static conditions. This impairment could be partially ameliorated by administration of rhHGF. This proof-of-concept study provides a way to study of more complex interactions, such as a co-culture with fibroblasts, endothelial cells, or immune cells, as well as the study of wound healing at an air–liquid interface.

Keywords: Wound Healing, organ-on-a-chip (OOC), air-blood barrier, Cyclic stretch, Idiopathic pulmonary fibrosis (IPF)

Received: 27 Sep 2018; Accepted: 03 Jan 2019.

Edited by:

Qasem Ramadan, Agency for Science, Technology and Research (A*STAR), Singapore

Reviewed by:

Andrea Peloso, Policlinico San Matteo Fondazione (IRCCS), Italy
Samy Gobaa, Institut Pasteur, France  

Copyright: © 2019 Felder, Trüeb, Stucki, Borcard, Stucki, Schnyder, Geiser and Guenat. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Olivier Guenat, University of Bern, ARTORG Center for Biomedical Engineering, Bern, 3012, Bern, Switzerland,