Toxicity Test of Total Particulate Matter in Mainstream Cigarette Smoke Based on Lung‐Hepatocyte Vascularised Microfluidic Chip

Microfluidic chips have relatively short test cycles, and their ability to reproduce tissue structure, environment and function with a certain degree of complexity greatly improves the accuracy of toxicity test models. In this study, a vascularised microfluidic chip containing lung‐hepatocytes was constructed to test the toxicity of total particulate matter (TPM) in mainstream cigarette smoke. After exposure to TPM for 3 consecutive days, there was a significant increase in LDH release from chip cells, significant changes in the MUC5AC and ZO‐1 proteins of Calu‐3 and a significant increase in the relative expression level of the CYP1A1 gene of HepG2 in a dose‐dependent manner. These results indicate that TPM can penetrate through Calu‐3 cultured at the air‐liquid interface in the upper chamber of the chip and HUVEC in the middle chamber, affecting HepG2 in the lower chamber. This reflects the entire in vivo exposure process of TPM under 3D conditions. The chip constructed in this study can assess key toxicological endpoints of TPM. It not only simulates the primary pulmonary response to TPM but also captures the subsequent hepatic metabolic activation. This provides a more comprehensive and physiologically relevant toxicity assessment and offers a new method for TPM toxicity testing.