| Pulmonary hypoplasia and pulmonary hypertension account for nearly 40-50% of the mortality rate among newborn human babies. Impaired lung growth in babies has led pediatric surgeons to investigate regulators for lung development, and to design strategies to overcome hypoplasia and promote prenatal lung growth prenatally. Throughout development, the lung is filled with liquid and is influenced by mechanical factors like lung liquid induced stretch, fetal breathing movements and airway peristalsis (AP). Although it is well documented that mechanical forces regulate lung growth and maturation, their precise effect is still not completely understood. Computational models simulating the mechanical environment in which lung develops can help us understand the role of these physical forces. In this study we have used measurements and estimates from developing embryonic lung to build a computational fluid-structure model that simulates AP. Peristalsis towards a closed end has not been modeled before.;The objective of this study is to build a framework for understanding the mechanics of Airway Peristalsis (AP) in the embryonic lung. This model will allow us to make predictions about the effects of AP on prenatal growth. As a pilot study it also provides important results that can be used for building more complex models of airway contractions.;Our simulations suggest several interesting results affecting cellular mechanotransduction in the different regions of the lung. First, in the case of an open trachea, high fluid velocities and flow reversal over a period of one cycle can potentially regulate development through mechanosensing in the stalk region, but not in the distal end where flow is negligible. Second, the tissue stretch in the stalk is primarily influenced by the local smooth muscle load, however hydrostatic pressure regulates tissue stretch in the tips. Third, our parametric analysis shows that peak stresses and strains depend on the ratio FT/E, where F is the smooth muscle force density, T is the tissue thickness and E is the tissue stiffness. In the case of an open trachea, we observe that some of the peak stresses and strains were affected by lumen fluid viscosity. Fourth, depending on whether the trachea is open or closed we observe different flow phenomena and tissue deformations, suggesting that tracheal ligation can influence mechanosensing that might not have occurred under normal conditions.;Since some flow characteristics in the model depend on the viscosity, we measured the microviscosity of the lumen fluid in prenatal mouse lung using particle tracking microrheology (PTM). We determined the lumen fluid to be more viscous than blood. |
