Effects of inhaled particulate matter on alveolar collapse and respiratory disease using inkjet bioprinted three-dimensional alveolar barrier

Abstract

Particulate matter (PM) travels into our body via the airway tract and causes damages to our respiratory system. This damage induced many pulmonary diseases, so it is significant to analyze the effect of PM on the respiratory system. For this reason many studies have been investigated, however, most of them have carried out in 2D cell culture, animal models and epidemiological investigation. In order to verify the exact mechanisms of PM, it is necessary to examine using 3D structured model which mimics human alveoli. In this study, we applied atmospheric PM, Arizona test dust A1 on our previously developed 3D alveolar barrier model which generated by inkjet bioprinting process. As a result, our bioprinted alveolar barrier model was exposed to PM, we observed dramatic cell death and decreased proliferation rate. Based on the damages in cellular levels, we also observed an increased pro-inflammatory cytokines, IL-1β and TNF-α, which stiumulates the secretion of matrix metalloproteinase(MMP)-1 and -9. To analyze the effect of increased immune responses caused by PM, we treated PM in dose- and time-dependent manner and then confirmed an alveolar tissue disintegration which might induce a collapse of the structure and a decreased barrier tightness. We further investigated a cancer-related and pulmonary surfactant protein-related genes in PM-treated alveolar tissue then we could estimate the possible harmful effect of PM on lung cancer and surfactant dysfunction. This study demonstrated the physiological impact of PM on cytotoxicity effects, alveolar barrier rigidity, surfactant secretion, and pulmonary diseases using inkjet bioprinted alveolar barrier in gene expression level. It has also been demonstrated that PM can have serious consequences that can lead to the collapse of the alveolar barrier. We expect that this strategy using in vitro inkjet bioprinted 3D alveolar barrier is able to be a valuable tool for the identification of air pollutant exposure-related diseases.