Development of a 3D bioengineered human lung submucosal gland ductal airway model to study mucociliary clearance in vitro

Mucociliary clearance (MCC) is critical in maintaining lung health and preventing respiratory infections. MCC is impaired in people with cystic fibrosis, due to accumulation of thick, sticky mucus resulting from defective cystic fibrosis transmembrane conductance regulator channel function. In this study, we developed a unique 3D lung submucosal gland ductal airway model utilizing primary human submucosal gland epithelial cells, which enables the formation of physiologically relevant architecture of the ductal epithelium including ciliary cells within a 3D bioprinted scaffold. Our observation demonstrates that this model not only enables the fabrication of human lung submucosal gland ductal airway-like structure mimicking <i>in vivo</i> physiology, also facilitates quantitative measurement of patient-specific MCC and determines pharmacological effects. Our results suggest that this model could be a valuable tool for understanding mechanisms underlying impaired MCC and testing the efficacy of novel therapeutic strategies for the treatment of respiratory diseases such as cystic fibrosis.