Determination of Benzopyrene-Induced Lung Inflammatory and Cytotoxic Injury in a Chemical Gradient-Integrated Microfluidic Bronchial Epithelium System.

Environmental pollution is one of the largest sources responsible for human diseases and premature death worldwide. However, the methodological development of a spatiotemporally controllable and high-throughput investigation of the environmental pollution-induced biological injury events is still being explored. In this study, we describe a chemical gradient generator-aided microfluidic cell system for the dynamic study of representative environmental pollutant-induced bronchial epithelium injury in a throughput manner. We demonstrated the stability and reliability of operation-optimized microfluidic system for precise and long-term chemical gradient production. We also performed a microenvironment-controlled microfluidic bronchial epithelium construction with high viability and structure integration. Moreover, on-chip investigation of bronchial epithelium injury by benzopyrene stimulation with various concentrations can be carried out in the single device. The varying bronchial inflammatory and cytotoxic responses were temporally monitored and measured based on the well-established system. The benzopyrene directionally led the bronchial epithelium to present observable cell shrinkage, cytoskeleton disintegration, Caspase-3 activation, overproduction of reactive oxygen species, and various inflammatory cytokine (TNF-α, IL-6, and IL-8) secretion, suggesting its significant inflammatory and cytotoxic effects on respiratory system. We believe the microfluidic advancement has potential applications in the fields of environmental monitoring, tissue engineering, and pharmaceutical development.