3.2 Modeling and characterizing fire-related SI-ALI on the LOC
The combustion control system and non-metallic materials, including polyimide foam, rubber, sound insulation pads, acrylic paint, floor adhesive, nitrile rubber, and modified ethylene resin, are illustrated in Figures 2B-a and 2B-c. Combustion byproducts were monitored using a portable Fourier Transform Infrared Spectrometer (FTIR) (Figure 2B-b). To evaluate combustion stability, emissions of gases, including nitrous oxide (N₂O), carbon monoxide (CO), styrene (C₈H₈), and hydrogen cyanide (HCN), were quantified. The results showed consistent trends in the concentration changes of these gases across different batches of material during combustion (Supplementary Figure 2C), with detailed compositions provided in Supplementary Text 1.
To replicate the SI-ALI process observed in vivo (Figures 1A and 3F), the collected smoke was introduced into the lower compartments of the lung chip using a syringe to simulate alveolar smoke exposure (Figure 2C). Oxidative stress and apoptosis assays demonstrated increased ROS production (Figure 3C) and elevated cell apoptosis (Figure 3A) following smoke exposure. Transmission electron microscopy (TEM) revealed significant damage to the mitochondria and endoplasmic reticulum (Figure 3E). Leakage assays detected the rapid translocation of macromolecular substances (FITC-dextran, 40 kDa) from the vascular to the alveolar channel under smoke exposure (Figure 3B), indicating a compromised alveolar-capillary barrier. Additionally, a marked increase in the adhesion of activated THP-1 cells to the barrier was observed in the smoke-exposed group compared to the control group (Figure 3D). Inflammation- and apoptosis-related genes, including IL-6, TNF-α, and caspase-3, were upregulated in both epithelial and endothelial cells (Figure 4A-b, c, e), while IL-1β and NF-κB were predominantly upregulated in epithelial cells alone (Figure 4A-a, f). Notably, IL-10 expression remained unchanged (Figure 4A-d). ELISA results further confirmed that smoke exposure stimulates the release of TNF-α, IL-6, and IL-1β, independent of THP-1 cell presence (Figure 4B). These findings underscore the detrimental impact of smoke on the alveolar-capillary barrier, including the induction of oxidative stress, cellular apoptosis, mitochondrial damage, and the initiation of an inflammatory cascade accompanied by enhanced inflammatory cell adhesion.