Assessment of the toxicity of acrolein on an alveolus microphysiological system

With the advancement of industrialization, public concerns about air pollution have been increasing. As the primary site of gas exchange in the respiratory system, the human lung is highly susceptible to the toxic effects of environmental pollutants. Among these, acrolein, an ubiquitous environmental contaminant, poses significant health risks to humans. In this study, we evaluated the impact of acrolein exposure using a novel alveolus microphysiological system (MPS), which mimics the key alveolar-capillary unit via the co-culturing of human alveolar epithelial cells and microvascular endothelial cells under fluid flow conditions. Following acrolein exposure, marked injuries were observed on the chip, including disrupted alveolar-capillary barrier, increased pro-inflammatory cytokine release, disruption of metabolic function, and mitochondrial impairment. Furthermore, we performed a drug screening on the alveolus MPS, which showed dexamethasone and prednisolone could partially mitigate acrolein-induced alveolar injury in the model. Together, these findings demonstrate that the alveolus MPS can quickly probe human lung responses to acrolein exposure, providing a human-relevant alternative for the rapid assessment of health risks posed by environmental pollutants.