Significance This work reports the development of a physiologically relevant human alveolar lung-on-a-chip model, composed of a three-dimensional (3D) porous hydrogel made of gelatin methacryloyl (GelMA) featuring an inverse opal structure, bonded to a compartmentalized chip device that provides air–liquid interface and cyclic breathing motions. Significantly, this GelMA structure has a high similarity to native human alveolar sacs in that they both possess sac-like pores and interconnecting windows between the sacs, in addition to a stiffness similar to the native human distal lung. We showed through multiscale analyses that our 3D GelMA inverse opal structure was better able to maintain the functions of primary human alveolar epithelial cells in a more in vivo-like manner compared with planar models. 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.
【저자키워드】 alveoli, three-dimensional, lung-on-a-chip, inverse opal, distal lung,