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

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.