Collagen Tube-Based Model to Study Small Airway Collapse-Reopening Dynamics

The human respiratory system consists of a hierarchical network of extracellular matrix based tubular structures, lined by an epithelium that is exposed to complex biomechanical stimuli. Airway collapse-reopening dynamics has previously been studied numerically and in experiments performed in synthetic polymer tubes. Microfluidic airway-on-a-chip models have replicated the spatial arrangement of different cells and circumferential stretch. Their reliance on rigid synthetic membranes or walls however fails to mimic the composition, softness and resulting compliance of human airways. Here, we present a soft 3D collagen-based, tubular airway model with a lumen lined by an epithelial layer. The collapsible, stretchable, and perfusable nature of this structure recapitulates physiological airway dynamics, including wall shear stress, cyclic stretch, overdistension, as well as compliant repetitive collapse and reopening phenomena.

Relationships between the transmural pressure and the tube cross section favorably compare with previous studies performed in synthetic tubes. We further explore conditions relevant to ventilation induced lung injury and captured both the overdistension as well as the collapse and reopening scenarios. Our findings suggest the former to not significantly affect cell viability while the latter lead to acute cell death. We observed that increasing expiratory airflow resistance resulted in a slower collapse velocity and reduced severity of cell injury. The integrity of the epithelial barrier was compromised during repetitive collapse and reopening cycles but remained intact during overdistension. Our extracellular matrix based small airway model provides a valuable and adaptable platform for studying lung physiology, particularly related to conditions relevant in ventilation-induced lung injury. The ability to replicate the complex biomechanical microenvironment of the respiratory system enhances our understanding of small airway epithelial function and disease progression.



The presented approach enhances our understanding of lung physiology, especially for ventilation-induced lung injury, while holding promise for broad application in organ-on-a-chip models for different tubular tissues.