“…Recapitulating lung tissue in vitro is challenging due to the complexity of the organ, which contains various components such as an air-exposed epithelium, a structurally intrinsic extracellular matrix, a complex vasculature network, and a myriad of immune components ( 203 ) ( Figure 1 ), as well as a unique microbiome that contributes to the exchange of chemical signals in this microenvironment ( 6 , 204 , 205 ). The airway itself varies in shape and size, transitioning from the bronchi to bronchioles to the alveoli, reflecting a change in function from a conducting section to a gas exchange section ( 200 , 202 , 206 ), as well as regional differences in cell phenotypes and histology. For example, the small airways are lined with pseudostratified columnar ciliated epithelium with interspersed mucin secreting goblet cells; these features are functionally equipped to generate and move mucus, an important immune defense against extracellular microbes ( 136 , 207 , 208 ).…”