(E-182) Design and Fabrication of an Asymmetric Three-Dimensional Neonate Lung Model to Study Surfactant Transport in the Airways

Introduction:: Neonatal Respiratory Distress Syndrome (NRDS) affects pre-term infants with underdeveloped lungs. Lack or insufficient pulmonary surfactant in NRDS results in high surface tension forces in alveoli and can lead to lung collapse (1,2). NRDS treatment consists of intratracheal delivery of an exogenous surfactant known as surfactant replacement therapy. The objective of the treatment is to form a surfactant plug in the trachea and propagate it downstream using forced air to continuously split the plug(s) in airway bifurcations and deliver surfactant to alveoli. A uniform distribution of the instilled surfactant is critical to restore normal breathing. However, the inability to safely image pre-term infants’ lungs hinders direct evaluation of treatment success. The goal of this study was to develop a 3D physiologic neonate lung airway model and investigate the distribution of instilled surfactant in airways.

Materials and Methods::
An eight-generation, 3D, asymmetric lung airway model was designed in SolidWorks (Figure 1a) and fabricated using stereolithography (Formlabs, INC) with a semi-transparent, rigid material (Clear V4 resin) (Figure 1b). The model was cleaned thouroughly by agitating in an isopropaly alcohol bath and soaking for 24 hours. Prior to experiments, each model was rendered hydrophilic using oxygen plasma (Harrick Plasma) and the inside of the airway was pre-wet using distilled water. A 140 uL plug of Infasurf surfactant (ONY, Inc) was instilled in the trachea (airway generation z=0) and propagated using forced air from a syringe pump (Chemyx) at a Capillary number of Ca=0.016 to represent physiologic flow. The propagation of the plug was recorded at 25 fps using four cameras from the front, side, top, and bottom views.









Results, Conclusions, and Discussions::
We designed an asymmetric neonatal lung model from morphometric data of human adult lungs, including length, diameter, tapering of airways, rotation of airways in the gravitational space, and bifurcation angle between airways (3,4). We scaled the measurements of each airway from an adult lung to a neonate lung using a scaling factor developed by dividing the diameter of the neonate trachea (3.5 mm) by the diameter of the adult trachea (20.0 mm). Each adult airway size was multiplied by the scaling factor to obtain the size of the neonate airway. Using these dimensions, we constructed the eight-generation airway tree as a single part in SolidWorks starting with the trachea (z=0). We attached the next generation (z=1) by creating a bifurcation. To create the bifurcation, we started with a sketch outline (Figure 2a) (5). We then added a plane to the sketch, created the outside diameter of the bifurcation zone, used the loft feature to develop the bifurcation zone and hollowed out the airway using the loft cut feature (Figure 2b-2d). Using similar steps, we connected the z=1 airway to the bifurcation zone (Figure 2e, 2f). We continued this progression creating a full asymmetric eight-generation neonate lung model. Similar to native airways, this model contains three lobes of airways in the right lung and two lobes of airways in the left lung (Figure 1a). We used the computational model to successfully fabricate a physical model. We then placed a plug of Infasurf surfactant in the trachea and propagated it through the airways (Figure 3). We will quantify the distribution and efficiency of the surfactant. The distribution index is defined as the volume of surfactant that enters each of the five lobes to the instilled volume. The efficiency index is defined as the percentage of the instilled dose to reach the fifth-generation airways. We successfully designed a 3D asymmetric neonatal lung model. Our semi-transparent eight-generation lung model will guide future studies to successfully quantify the distribution and efficiency of surfactant transport through the airways. Further developments of this model will consider cyclic breathing and offer practical insights into improving surfactant replacement therapy.




Acknowledgements (Optional): :
Financial support from NSF grant 1904210.




References (Optional): :
1. Tavana, H. et al., Lab. Medicine, 2009. 40: p. 203-209. 2. Stevens, T.P. et al., Chest, 2007. 121: p. 1577-1582. 3. Weibel, E.R et al., Science, 1962. 137: p. 577-585. 4. Raabe, O.G. et al., Lavelace Foundation, 1976.




5. Copploe, A. et al., Ann Biomed Eng, 2019, 47: p. 1435-1445.