4.7 Article

Second-generation lung-on-a-chip with an array of stretchable alveoli made with a biological membrane

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COMMUNICATIONS BIOLOGY
卷 4, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s42003-021-01695-0

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  1. Swiss National Science Foundation [185365]

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A new generation lung-on-a-chip utilizing a biological membrane made of collagen and elastin has been developed to mimic an array of tiny alveoli with in vivo-like dimensions. This membrane outperforms traditional PDMS in terms of stability, biodegradability, and tunability, offering the potential to more accurately reproduce air-blood barrier functions.
The air-blood barrier with its complex architecture and dynamic environment is difficult to mimic in vitro. Lung-on-a-chips enable mimicking the breathing movements using a thin, stretchable PDMS membrane. However, they fail to reproduce the characteristic alveoli network as well as the biochemical and physical properties of the alveolar basal membrane. Here, we present a lung-on-a-chip, based on a biological, stretchable and biodegradable membrane made of collagen and elastin, that emulates an array of tiny alveoli with in vivo-like dimensions. This membrane outperforms PDMS in many ways: it does not absorb rhodamine-B, is biodegradable, is created by a simple method, and can easily be tuned to modify its thickness, composition and stiffness. The air-blood barrier is reconstituted using primary lung alveolar epithelial cells from patients and primary lung endothelial cells. Typical alveolar epithelial cell markers are expressed, while the barrier properties are preserved for up to 3 weeks. Zamprogno et al. report a lung-on-a-chip of the second generation that mimics an array of alveoli with in vivo-like dimensions, based on a thin, stretchable collagen-elastin membrane used to reproduce the air-blood barrier functions. The membrane is stable, can be cultured on both sides for weeks, is biodegradable and its elastic properties allow mimicking respiratory motions by mechanically stretching the cells.

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