Design of a System with a 3D Biomimetic Stretchable Substrate for Maintenance and Study of Alveolar Epithelial Cells

Traditional in vitro alveolar epithelial cell (AEC) models lack physiological architectural cues required for regulating cell functionality. While 3D AEC organoids incorporate some characteristics of alveolar microarchitecture, they are challenging to analyze, not easily scalable, and their architecture cannot be easily controlled. Lung-on-Chips have successfully reproduced some key features of lung tissue through customized microenvironments with precise mechanical, fluidic, and structural control. However, these models lack the geometry of alveolar lumen. Thus, we developed an Alveoli-on-a-Chip that mimicked alveolar curvature and distension during respiration. We demonstrated that cells were viable and responsive to patterns of tensional forces in our chip. Additionally, through characterization of YAP localization and actin remodeling, we showed that our chip is able to recapitulate mechanosensitive response of AECs to architectural cues. We envision this technology will provide a platform to maintain iPSC derived distal epithelial cells that will be valuable for disease modeling and drug testing.M.H.Sc