A next-generation system for smoke inhalation integrated with a breathing lung-on-chip to model human lung responses to cigarette exposure DOI Creative Commons
Arunima Sengupta, Simone Schmid,

Noémie Grangier

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: May 25, 2025

Continuous exposure to cigarette smoke (CS) significantly contributes the development and progression of chronic obstructive pulmonary disease (COPD) lung cancer. Animal models that inhale nasally have different physiology from humans may not accurately replicate smoke-induced health effects. Furthermore, traditional in vitro fail lung's dynamic mechanical forces realistic inhalation patterns, limiting their relevance preclinical research. Here, we introduce an advanced inhalation-based lung-on-chip system, Flow AX12 (CFAX12), investigate CS-induced cellular responses a physiologically relevant manner. Unlike previous technologies, CFAX12 integrates cyclic stretch with controlled whole-smoke exposure, allowing for more accurate recreation alveolar microenvironment dynamics barrier integrity responses. Using human epithelial cells, microvascular endothelial macrophages mono- co-culture under air-liquid interface (ALI) conditions breathing-like (Str), simulated key features. Our results show CS using induced ~ 60% reduction trans-barrier electrical resistance (TER), increased ROS generation depending on model complexity, 4.5-fold increase IL-8 gene expression, all hallmarks early COPD pathogenesis. These findings underscore damage, inflammation, oxidative stress, which contribute dysfunction progression. Also, provides alternative submerged extract (CSE) treatments, offering VC10 Smoking Robot, ensuring precisely regulated delivery. Additionally, inclusion surfactant reduced IL8 levels by 5 folds. Hence, integrating biological offers robust platform assessing inhaled effects identifying therapeutic targets. It's application drug screening can facilitate discovery compounds preserve integrity, reduce mitigate ultimately bridging gap between regulatory research applications.

Language: Английский

A next-generation system for smoke inhalation integrated with a breathing lung-on-chip to model human lung responses to cigarette exposure DOI Creative Commons
Arunima Sengupta, Simone Schmid,

Noémie Grangier

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: May 25, 2025

Continuous exposure to cigarette smoke (CS) significantly contributes the development and progression of chronic obstructive pulmonary disease (COPD) lung cancer. Animal models that inhale nasally have different physiology from humans may not accurately replicate smoke-induced health effects. Furthermore, traditional in vitro fail lung's dynamic mechanical forces realistic inhalation patterns, limiting their relevance preclinical research. Here, we introduce an advanced inhalation-based lung-on-chip system, Flow AX12 (CFAX12), investigate CS-induced cellular responses a physiologically relevant manner. Unlike previous technologies, CFAX12 integrates cyclic stretch with controlled whole-smoke exposure, allowing for more accurate recreation alveolar microenvironment dynamics barrier integrity responses. Using human epithelial cells, microvascular endothelial macrophages mono- co-culture under air-liquid interface (ALI) conditions breathing-like (Str), simulated key features. Our results show CS using induced ~ 60% reduction trans-barrier electrical resistance (TER), increased ROS generation depending on model complexity, 4.5-fold increase IL-8 gene expression, all hallmarks early COPD pathogenesis. These findings underscore damage, inflammation, oxidative stress, which contribute dysfunction progression. Also, provides alternative submerged extract (CSE) treatments, offering VC10 Smoking Robot, ensuring precisely regulated delivery. Additionally, inclusion surfactant reduced IL8 levels by 5 folds. Hence, integrating biological offers robust platform assessing inhaled effects identifying therapeutic targets. It's application drug screening can facilitate discovery compounds preserve integrity, reduce mitigate ultimately bridging gap between regulatory research applications.

Language: Английский

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