Reversed-engineered human alveolar lung-on-a-chip model

Huang, Di; Liu, Tingting; Liao, Junlong; Maharjan, Sushila; Xie, Xin; P�rez, Montserrat; Anaya, Ingrid; Wang, Shiwei; Mayer, Alan Tirado; Kang, Zhixin; Kong, Weijia; Mainardi, Valerio Luca; Garciamendez-Mijares, Carlos Ezio; Mart�nez, Germ�n Garc�a; Moretti, Matteo; Zhang, Weijia; Gu, Zhongze; Ghaemmaghami, Amir M.; Zhang, Yu Shrike

Abstract

Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.

Citation

Huang, D., Liu, T., Liao, J., Maharjan, S., Xie, X., Pérez, M., Anaya, I., Wang, S., Mayer, A. T., Kang, Z., Kong, W., Mainardi, V. L., Garciamendez-Mijares, C. E., Martínez, G. G., Moretti, M., Zhang, W., Gu, Z., Ghaemmaghami, A. M., & Zhang, Y. S. (2021). Reversed-engineered human alveolar lung-on-a-chip model. Proceedings of the National Academy of Sciences, 118(19), Article e2016146118. https://doi.org/10.1073/pnas.2016146118

• Journal Article Type: Article
• Acceptance Date: Apr 2, 2021
• Online Publication Date: May 3, 2021
• Publication Date: May 11, 2021
• Deposit Date: May 11, 2021
• Publicly Available Date: May 11, 2021
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Print ISSN: 0027-8424
• Electronic ISSN: 1091-6490
• Publisher: National Academy of Sciences
• Peer Reviewed: Peer Reviewed
• Volume: 118
• Issue: 19
• Article Number: e2016146118
• DOI: https://doi.org/10.1073/pnas.2016146118
• Keywords: Multidisciplinary
• Public URL: https://nottingham-repository.worktribe.com/output/5521505
• Publisher URL: https://www.pnas.org/content/118/19/e2016146118