Models of Surfactant Replacement Therapy in Neonatal Lungs

Surfactant replacement therapy (SRT) is a widely used treatment for neonatal respiratory distress syndrome (NRDS), a condition caused by surfactant deficiency that leads to alveolar collapse and impaired gas exchange. While SRT has significantly improved clinical outcomes for neonates, challenges remain in achieving uniform and effective surfactant delivery throughout the lung. This review provides an overview of the pulmonary surfactant, lung development, and the underlying causes of NRDS to establish the physiological context of SRT. We then examine key advancements in experimental and computational modeling approaches that have been used to study surfactant transport and optimize delivery techniques. Computational models have provided insight into fundamental aspects of transport of surfactant as liquid boli or aerosols and the influence of airway geometry on surfactant spreading on airway walls and distribution in the airway tree. Benchtop models, including 3D multigeneration airway models and planar microfluidic devices, have enabled experimental control and visualization of surfactant spreading in airways. And studies using animal models have enabled testing different dosing strategies and delivery methods with full lung models, albeit interspecies differences in the lung anatomy make direct translation to humans difficult. Together, research using these models has highlighted the importance of optimizing delivery parameters such as dose volume, instillation flow rate, aerosol particle size, and lung orientation to improve therapeutic outcomes. The integration of these multidisciplinary approaches is critical to advance next-generation SRT strategies that are more efficient, less invasive, and better suited to the unique physiology of preterm infants.