Description
Pulmonary surfactant deficiency or dysfunction is associated with several respiratory pathologies, including neonatal respiratory distress syndrome (RDS). In premature infants, lung immaturity limits surfactant production, increasing alveolar surface tension and causing severe breathing difficulties. To treat this condition, surfactant replacement therapy (SRT), based on intratracheal instillation of exogenous surfactant, was developed and has proven highly effective in neonates, becoming standard clinical practice.
SRT was later explored in adults, particularly for acute respiratory distress syndrome (ARDS), but clinical outcomes have been inconclusive. We hypothesize that this discrepancy arises from differences in surfactant distribution between adult and neonatal lungs, due to the greater geometric complexity of the pulmonary tree and the presence of an airway mucus layer.
To date, exogenous pulmonary surfactant propagation has been studied mainly through theoretical models and numerical simulations[1], while experimental investigations remain scarce[2]. In particular, surfactant–mucus interactions and their impact on surfactant distribution in branched adult airway geometries have not been systematically explored.
Here, we propose a microfluidic approach to experimentally study the propagation of exogenous pulmonary surfactant (Curosurf®) in simplified geometries that mimic distal pulmonary airway bifurcations. These bifurcations, representative of the last generations of the airways in adults, are regions where geometric confinement, capillarity, and interfacial effects are dominant, and where the most relevant surfactant–mucus interaction phenomena are expected to occur during propagation.
The system is based on PDMS microfluidic bifurcations, in which the surfactant is introduced in the form of plugs generated via classical T-junction configuration [3–5].
In a first stage, the study focuses on uncoated microfluidic devices, with the aim of establishing a reproducible experimental baseline for surfactant distribution in simple bifurcations. In a later stage, the system evolves toward more biomimetic configurations by incorporating polymeric coatings based on snail mucin as a model of pulmonary mucus, in order to investigate how the presence of this viscoelastic layer affects surfactant propagation and distribution in pulmonary bifurcations.
[1] Filoche, M., Tai, C. F., & Grotberg, J. B. (2015). Three-dimensional model of surfactant replacement therapy. Proceedings of the National Academy of Sciences, 112(30), 9287-9292.
[2] Kazemi, A., Louis, B., Isabey, D., Nieman, G. F., Gatto, L. A., Satalin, J., ... & Filoche, M. (2019). Surfactant delivery in rat lungs: Comparing 3D geometrical simulation model with experimental instillation. PLoS Computational Biology, 15(10), e1007408.
[3] Baroud, C. N., Gallaire, F., & Dangla, R. (2010). Dynamics of microfluidic droplets. Lab on a Chip, 10(16), 2032-2045.
[4] Garstecki, P., Fuerstman, M. J., Stone, H. A., & Whitesides, G. M. (2006). Formation of droplets and bubbles in a microfluidic T-junction—scaling and mechanism of break-up. Lab on a Chip, 6(3), 437-446.
[5] Ody, C. P., Baroud, C. N., & De Langre, E. (2007). Transport of wetting liquid plugs in bifurcating microfluidic channels. Journal of colloid and interface science, 308(1), 231-238.