Abstract The lungs play a critical role in gas exchange and overall respiratory functions, relying on a delicate balance of pulmonary mechanics and surfactant homeostasis. Surfactant replacement therapy (SRT) is a life-saving intervention for conditions such as neonatal respiratory distress syndrome (NRDS), where surfactant deficiency impairs alveolar stability and normal gas exchange. To improve treatment strategies of lung disorders such as NRDS, researchers have developed a variety of computational, benchtop, and animal models to investigate surfactant transport and drug delivery in the lungs. This review explores the evolution of lung modeling approaches, from computational fluid dynamics simulations to physical macroscale airway models and microfluidic lung-on-a-chip devices, highlighting their contributions to our understanding of pulmonary mechanics and therapeutics transport in the lungs. While computational and benchtop models provide valuable insights into fluid dynamics of propagation and deposition of instilled or inhaled therapeutics in airways, they lack the dynamic compliance and biomechanical properties of a functioning lung. Animal models, such as ex vivo rat lungs, remain essential for bridging this gap, allowing researchers to validate findings under physiologically relevant conditions. By integrating these approaches, researchers can refine intratracheal drug delivery techniques, enhance aerosolized and liquid surfactant therapies, and develop more effective treatments for respiratory diseases.
Combs et al. (Mon,) studied this question.