A Three-Dimensional Model of Human Lung Airway Tree to Study Therapeutics Delivery in the Lungs.

Abstract

Surfactant instillation into the lungs is used to treat several respiratory disorders such as neonatal respiratory distress syndrome (NRDS). The success of the treatments significantly depends on the uniformity of distribution of the instilled surfactant in airways. This is challenging to directly evaluate due to the inaccessibility of lung airways and great difficulty with imaging them. To tackle this problem, we developed a 3D physical model of human lung airway tree. Using a defined set of principles, we first generated computational models of eight generations of neonates' tracheobronchial tree comprising the conducting zone airways. Similar to native lungs, these models contained continuously-branching airways that rotated in the 3D space and reduced in size with increase in the generation number. Then, we used additive manufacturing to generate physical airway tree models that precisely replicated the computational designs. We demonstrated the utility of the physical models to study surfactant delivery in the lungs and showed the effect of orientation of the airway tree in the gravitational field on the distribution of instilled surfactant between the left and right lungs and within each lung. Our 3D lung airway tree model offers a novel tool for quantitative studies of therapeutics delivery.