Disrupting Experimental Strategies for Inhalation Toxicology: The Emergence of Microengineered Breathing-Smoking Human Lung-on-a-Chip

Abstract

Cigarette smoking is major public health problem and a substantial contributor to the pathogenesis of respiratory disorders such as chronic obstructive pulmonary disease and lung cancer. In addition, our society faces the rapidly growing use of tobacco-related products such as electronic cigarettes. Thus, we need reliable model systems that can accurately predict the biological impact of exposure to inhaled smoke and vape and allow recreation of clinically relevant organ-level responses. In this study, we describe the emergence of ''Breathing-Smoking Human Lung-on-a-Chip'' microdevice at the interface of tissue microengineering, pulmonary biology, toxicopathology, and systems biology to enable study of smoke-induced lung injuries with high fidelity and precision in vitro. We also address the ability of this novel microfluidic system to overcome several major limitations of widely used animal models and static in vitro cultures of smoke exposure. While at its infancy, this technological advancement offers significant potential on how experimental inhalation toxicity studies can be performed.

Emerging Technologies for In Vitro Inhalation Toxicology

“…It could also determine the relevant in vivo pharmacokinetic parameters such as mean Lethal Dose (LD50) or half-maximal inhibitory concentration (IC50). [59]…”

Advances in Smoking Related In Vitro Inhalation Toxicology: A Perspective Case of Challenges and Opportunities from Progresses in Lung-on-Chip Technologies

“…For the purpose of identifying the adverse effects of smoke inhalation, the researchers essentially connected the custom-made smoke machine to the LOC microfluidic device. 68 Researchers are further developing a smoking block for a tobacco product, ecigarettes, and e-liquids to investigate smoking-induced abnormal biological responses that happen in the microengineered small areas of different lung regions, particularly designing microalveoli-on-chip format. 62 A very convincing evidence on the tissue affected form such a study was found to be consistent with data from literature.…”

“…Tobacco product-induced/associated lung injuries and diseases remain a very important public health concern in both developed and developing countries. For the purpose of identifying the adverse effects of smoke inhalation, the researchers essentially connected the custom-made smoke machine to the LOC microfluidic device . Researchers are further developing a smoking block for a tobacco product, e-cigarettes, and e-liquids to investigate smoking-induced abnormal biological responses that happen in the microengineered small areas of different lung regions, particularly designing microalveoli-on-chip format .…”

Airway-On-A-Chip: Designs and Applications for Lung Repair and Disease

“…Once established, a dynamic ALI can also be utilized to conduct exposure studies in a more physiologically and clinically relevant context [ 6 ]. Benam et al created a custom smoking machine to replicate biomimetic exposure, however their non-exposed systems remain in a semi-dynamic state [ 59 ].…”

“…In general, co-culture systems are more physiological relevant, as they mimic the complex in vivo microenvironment better than monoculture systems and can be utilized to investigate direct and indirect cell-to-cell interactions that occur between homotypic and heterotypic cell populations. With appropriate cell selection, ALI and shear forces it has been shown that lung-on-a-chip models have the ability to replicate lung barrier function [ 20 , 23 , 26 , 49 , 55 ], lung injury [ 17 , 18 ], inflammation [ 23 , 26 , 49 ], and immune response to cigarette smoke [ 23 , 59 ] and infection [ 23 , 27 , 48 , 55 ].…”