Conclusion
In summary, our study is the first to utilize organ-on-a-chip and
organoid technologies, optimizing both the smoke generation process and
chip design to create a model that closely replicates contemporary
fire-related smoke-induced lung injury. By integrating advanced
technologies such as proteomics and computational biology, alongside
organoid technology and animal models, we identified potential
pathogenic pathways and genes. Simultaneously, various cell types’
responses to smoke injury were analyzed at the organ level, and
potential therapeutic drugs and combinations were screened. This
approach provides a powerful tool for studying the mechanisms and
developing treatments for fire-related SI-ALI. However, there are areas
for improvement in our study. First, the chip model primarily focuses on
early lung injury, neglecting late-stage pathologies such as fibroblast
activation and extracellular matrix deposition that may occur following
smoke exposure. These factors can contribute to the development of
pulmonary fibrosis, significantly impairing respiratory function and
affecting patients’ quality of life, with currently no effective
treatments available. Therefore, future research should delve deeper
into the mechanisms of pulmonary fibrosis induced by smoke exposure.
Additionally, while the results obtained from the A549 cell line were
validated using lung organoids, future studies should consider employing
primary lung epithelial cells to more authentically replicate the
pathophysiological processes of the lung. Furthermore, the bidirectional
flow provided by the perfusion system, along with the absence of
neutrophils in the immune cell population, may influence the model’s
injury responses, warranting further optimization in subsequent
research. Lastly, this study did not incorporate mechanical stretching
of the lung. Previous research indicates that respiratory motion can
affect the pathophysiological processes of the lung
barrier[62], and rapid breathing can lead to shear
stress[61] injuries during smoke exposure,
potentially exacerbating lung damage. This complexity may complicate the
investigation of mechanisms related to smoke-induced toxicity.
Consequently, a static model was selected for this study. Future
research will build upon these findings to further investigate the
mechanisms of smoke-induced lung injury under conditions of respiratory
motion.