Transport of Clinical Surfactant in a Three-Dimensional Lung Model of Neonates: A Quantitative Experimental-Computational Study*

Neonatal respiratory distress syndrome is mainly treated with the intratracheal delivery of pulmonary surfactants. The success of the therapy depends on the uniformity of distribution and efficiency of the delivery of the instilled surfactant solution to the respiratory zone of the lungs. Direct imaging of the surfactant distribution and quantifying the efficiency of delivery is not feasible in neonates. To address this major limitation, we designed an eight-generation model of neonate lung airway tree using morphometric and geometric data of human lungs and fabricated it using additive manufacturing. Using this model, we performed systematic experimental studies of delivery of a clinical surfactant either at a single aliquot or at two aliquots under different orientations of the airway tree in the gravitational space to mimic rolling a neonate on their side during the procedure. In addition, we developed an efficient computational fluid mechanics algorithm based on the concept of Pore Network Models (PNM) to simulate the delivery of clinical surfactants in complex biological transport networks. The computational algorithm is used to explore the delivery and distribution of clinical agents in lung networks for a wide range of input variables including lung orientations, instillation flow rates, and network morphology.  Our study offers both a novel lung airway model and new insights into the effects of the orientation of the lung airways and the presence of a pre-existing surfactant film on how the instilled surfactant solution distributes in airways.