Engineering a Dynamic Model of the Alveolar Interface for the Study of Aerosol Deposition

Nano and micro particles are widely used in industrial, household and medicinal applications. These dispersed particles can cause inflammation and stress in lung tissue, leading to the development of disease. Moreover, their effect on human tissue is complex and not completely understood, since it is mediated by different factors. To understand the complex interaction between particles and lung tissue, an in vitro model that mimics the alveolar microenvironment was designed. This system, named DALI (Dynamic model for ALveolar Interface), consists of an aerosol generator and a bioreactor with a moving membrane placed between an air-liquid interface to study drug and nanoparticles deposition and passage. To mimic natural breathing, an external compressed air system is used to stretch the membrane where alveolar epithelial cells are seeded. Finally, a Quartz Crystal Microbalance (QCM) was designed to quantify the amount of aerosolized nanoparticles on the cell layer. The system was validated in terms of liquid and air tightness, biocompatibility of the materials, and capability in applying a cyclic strain. A biohybrid electrospun membrane made of Bionate®:gelatin was selected to replicate the alveolar barrier, since it is porous, cell adhesive and elastic. Deposition measurements were performed using the QCM to verify its capability in quantifying the nebulized nanoparticles. Biological studies were also performed to investigate the effects of the cell culture media flow and mechanical stretch on the growing cells. Even if a cell culture protocol still need to be optimized and exposure tests still need to be performed, this system paves the way towards relevant studies of aerosol and drug delivery and toxicology.