Evaluation of toxicity of heated tobacco products aerosol and cigarette smoke to BEAS-2B cells based on 3D biomimetic chip model

It is still a controversial topic about evaluating whether heated tobacco products (HTP) really reduce harm, which involves the choice of an experimental model. Here, a three-dimensional (3D) biomimetic chip model was used to evaluate the toxicity of aerosols came from HTP and smoke produced by cigarettes (Cig). Based on cell-related experiments, we found that the toxicity of Cig smoke extract diluted four times was also much higher than that of undiluted HTP, showing higher oxidative stress response and cause mitochondrial dysfunction. Meanwhile, both tobacco products all affect the tricarboxylic acid cycle (TCA), which is manifested by a significant decrease in the mRNA expression of TCA key rate-limiting enzymes. Summarily, 3D Biomimetic chip technology can be used as an ideal model to evaluate HTP. It can provide important data for tobacco risk assessment when 3D chip model was used. Our experimental results showed that HTP may be less harmful than tobacco cigarettes, but it does show significant cytotoxicity with the increase of dose. Therefore, the potential clinical effects of HTP on targeted organs such as lung should be further studied. Schematic overview of the experimental design. (A) Preparation of aqueous aerosol extracts. (B) 3D chip model construction and working principle. (C) Detailed experimental evaluation. [Display omitted] •The in vitro 3D biomimetic chip model was used to better evaluate the controversial heated cigarette products, which solved the shortcomings of two-dimensional cell culture and animal models.•It is more obvious that the toxicity of traditional cigarettes is much higher than that of heated cigarette products, and the toxicity of cigarette extract diluted four times under the same number of puffs is higher than that of undiluted heated cigarettes. Both tobacco products cause oxidative stress damage to mitochondria, which may affect the tricarboxylic acid cycle in energy metabolism.•This study provides the necessary important data for risk assessment, proving that HTP may be less harmful than tobacco cigarettes, but it does show significant cytotoxicity with the increase of dosage.