Impaired wound healing of alveolar lung epithelial cells in a breathing lung-on-a-chip

Felder, Marcel (ARTORG Center, Medical Faculty, University of Bern, Bern, Switzerland) ; Trueeb, Bettina (ARTORG Center, Medical Faculty, University of Bern, Bern, Switzerland) ; Stucki, Andreas Oliver (ARTORG Center, Medical Faculty, University of Bern, Bern, Switzerland) ; Borcard, Sara (ARTORG Center, Medical Faculty, University of Bern, Bern, Switzerland ; School of Engineering, HES-SO Valais-Wallis, HEI, HES-SO // University of Applied Sciences Western Switzerland) ; Stucki, Janick Daniel (ARTORG Center, Medical Faculty, University of Bern, Bern, Switzerland ; AlveoliX, Bern, Switzerland) ; Schnyder, Bruno (School of Engineering, HES-SO Valais-Wallis, HEI, HES-SO // University of Applied Sciences Western Switzerland) ; Geiser, Thomas (Pulmonary Medicine Department, University Hospital of Bern, Bern, Switzerland) ; Guenat, Olivier Thierry (ARTORG Center, Medical Faculty, University of Bern, Bern, Switzerland ; AlveoliX, Bern, Switzerland ; Pulmonary Medicine Department, University Hospital of Bern, Bern, Switzerland ; Thoracic Surgery Department, University Hospital of Bern, Bern, 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 potentially 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.


Article Type:
scientifique
Faculty:
Ingénierie et Architecture
School:
HEI-VS
Institute:
Institut Technologies du vivant
Date:
2019-01
Pagination:
5 p.
Published in:
Frontiers in Bioengineering and Biotechnology
Numeration (vol. no.):
2019, vol. 7, article no. 3
DOI:
ISSN:
2296-4185
Appears in Collection:



 Record created 2020-01-17, last modified 2020-01-21

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