01847nas a2200313   4500000000100000000000100001008004100002260001500043653001800058653001700076100002200093700002000115700001900135700001900154700002100173700001400194700002600208700002300234700001600257700001800273700002000291700002200311245010600333856005500439300000900494490000600503520101000509022001401519       2021                            d  c2021-02-0510aBiotechnology10aCell biology1 aPauline Zamprogno1 aSimon Wüthrich1 aSven Achenbach1 aGiuditta Thoma1 aJanick D. Stucki1 aNina Hobi1 aNicole Schneider-Daum1 aClaus-Michael Lehr1 aHanno Huwer1 aThomas Geiser1 aRalph A. Schmid1 aOlivier T. Guenat00aSecond-generation lung-on-a-chip with an array of stretchable alveoli made with a biological membrane  uhttps://www.nature.com/articles/s42003-021-01695-0  a1-100 v43 aThe 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.  a2399-3642