Engineered Airway Models to Study Liquid Plug Splitting at Bifurcations: Effects of Orientation and Airway Size.

Abstract

Delivery of biological fluids, such as surfactant solutions, into lungs is a major strategy to treat respiratory disorders including respiratory distress syndrome that is caused by insufficient or dysfunctional natural lung surfactant. The instilled solution forms liquid plugs in lung airways. The plugs propagate downstream in airways by inspired air or ventilation, continuously split at airway bifurcations to smaller daughter plugs, simultaneously lose mass from their trailing menisci, and eventually rupture. A uniform distribution of the instilled biofluid in lung airways is expected to increase the treatments success. The uniformity of distribution of instilled liquid in the lungs greatly depends on the splitting of liquid plugs between daughter airways, especially in the first few generations from which airways of different lobes of lungs emerge. To mechanistically understand this process, we developed a bioengineering approach to computationally design three-dimensional bifurcating airway models using morphometric data of human lungs, fabricate physical models, and examine dynamics of liquid plug splitting. We found that orientation of bifurcating airways has a major effect on the splitting of liquid plugs between daughter airways. Changing the relative gravitational orientation of daughter tubes with respect to the horizontal plane caused a more asymmetric splitting of liquid plugs. Increasing the propagation speed of plugs partially counteracted this effect. Using airway models of smaller dimensions reduced the asymmetry of plug splitting. This work provides a step toward developing delivery strategies for uniform distribution of therapeutic fluids in the lungs.