Human lung cell models to study aerosol delivery – considerations for model design and development

•Numerous in vitro models can represent upper or lower respiratory tract.•Choice of model and mode of aerosol exposure depend on the relevant scenario.•(Co-culture) models can mimic healthy or diseased tissues.•Lung models complement other pre-clinical models, e.g. in silico or in vivo. Human lung tissue models range from simple monolayer cultures to more advanced three-dimensional co-cultures. Each model system can address the interactions of different types of aerosols and the choice of the model and the mode of aerosol exposure depends on the relevant scenario, such as adverse outcomes and endpoints of interest. This review focuses on the functional, as well as structural, aspects of lung tissue from the upper airway to the distal alveolar compartments as this information is relevant for the design of a model as well as how the aerosol properties determine the interfacial properties with the respiratory wall. The most important aspects on how to design lung models are summarized with a focus on (i) choice of appropriate scaffold, (ii) selection of cell types for healthy and diseased lung models, (iii) use of culture condition and assembly, (iv) aerosol exposure methods, and (v) endpoints and verification process. Finally, remaining challenges and future directions in this field are discussed. [Display omitted]