Airborne toxicological assessment: The potential of lung-on-a-chip as an alternative to animal testing

Recent studies have shown that there exists a direct relationship between environmental pollutants (PM2.5, smog), the respiratory system, and the morbidity and mortality of cardiovascular diseases. However, the mechanism and principle of how these harmful substances are deposited in lung tissues and impair lung function remain unclear. It is important to gain improved understanding of the interaction between environmental pollutants and human lungs. Owing to the complexity of air pollution and toxicological risks, it is difficult to predict and evaluate the response of human lungs toward the damage caused by air pollution. Although animal models can be used as a basis for toxicological classification, the toxic effect on the human body could be very different from that on animals owing to the distinctive features of different species. This article provides a comprehensive review of in vitro lung-on-a-chip technologies and their application in the toxicological assessment of environmental pollutants. A lung-on-a-chip uses a bionic structure mimicking the physiological characteristic of lungs, features of a real airway, and condition of the physiological airflow. Accordingly, it can be used to reveal the intrinsic interaction between lung tissues and particulate matter and provide new insights into the effect of the toxicology of environmental particles on lungs. In addition, the development of novel and optimized lung-on-a-chip devices and their application devices in the health assessment of air pollution are expected to overcome the limitations of the current in vitro toxicological tests. They are also anticipated to provide effective and accurate methods for drug screening and toxicity testing. Finally, the application potential of in vitro lung-on-a-chip models is emphasized in this review.