Table 1 Preclinical Platforms for ENDS Inhalation Toxicology. Various systems, living and non-living, bioengineered and non-bioengineered, reviewed in this article
System Classification | Components | Characteristics (Pros and Cons) | Provided Biological Information | Application Examples |
|---|---|---|---|---|
2D and 3D Static Cell Culture Models | Human lung epithelial cell lines (e.g., Beas-2B); TWI models of primary hAEpCs | Pros: 2D Cultures: easy to culture, amenable for medium-to-high throughput testing. TWIs: recreation of in vivo-seen differentiated airway epithelium. Cons: 2D Cultures: lack differentiation into mucociliated airway epithelium, do not capture inter-individual variability. TWIs: lack dynamic interaction between lung epithelium and systemic immune system, limited multicellularity, absence of blood-like fluidic flow and physiological vascular shear, lack sub-epithelial extracellular matrix. | Cytotoxicity, inflammatory response, oxidative stress. | BEAS-2B cells to investigate cytotoxicity and inflammatory response to EC aerosols. |
Lung Spheroids and Organoids | 3D structures mimicking airway and alveoli derived from lung cells, iPSCs or tumor cells | Pros: More closely mimic tissue architecture and cellular interactions. Cons: Lack vasculature, ALI, hard to control cell ratio and aggregate size, inability to recapitulate dynamic mechanical forces with blood and air flows. | Differentiation into various lung cell types, cellular interactions. | Bronchial spheroids (derived from BEAS-2B cells) to study response to diesel exhaust particles. |
Precision Cut Lung Slices (PCLS) | Uniform whole lung sections (150–500 µm thick) | Pros: Mimic cellular and architectural complexity of lung. Cons: Limited viability, lack vascular circulation, high variability, absence of epithelial ALI. | Tissue-level responses, antiviral responses. | Human PCLS to study effects of vaping extract and IAV infection. |
Animal Models | Mostly mice (e.g., C57BL/6) or rats (e.g., Sprague Dawley) | Pros: Systemic effects, multi-organ responses. Cons: Ethical concerns, interspecies differences, time-consuming. | Pulmonary and systemic inflammation, immune responses, toxicological outcomes. | Mice exposed to EC aerosols to study inflammatory and immune responses. |
Organs-on-Chips | Microfluidic devices populated with human cells (e.g., Lung Small Airway-on-a-Chip, Vasculature-on-a-Chip) | Pros: Reproduce tissue‒tissue interfaces, mechanical cues, vascular perfusion. Cons: Low throughput, costly, lack certain tissue complexities. | Lung pathophysiology, cytokine secretion, immune cell recruitment, therapeutic responses. | Human Lung Small Airway-on-a-Chip to study response to EC aerosols under physiologically relevant breathing conditions. |
Computational Approaches | QSAR models, CFPD-PBTK models | Pros: Predict toxicity and particle deposition, reduce animal usage. Cons: Require high-quality data, need validation, may not account for all physical and chemical interactions. | Predictive toxicology, pharmacokinetics, molecular interactions. | QSAR models to predict inhalation toxicity of ENDS chemicals. |
Physico-chemical Analyses | QCM, Cascade Impactors, NMR, GC-MS | Pros: Provide detailed chemical composition and physical characteristics. Cons: Often terminal endpoints, not real-time, scalability issues. | Particle size distribution, chemical composition, toxic compound identification. | QCM to quantify particulate mass from aerosols, GC-MS for chemical analysis of e-liquids. |
Bioinspired Robotics | HUMITIPAA | Pros: Simulate human vaping behavior and respiration mechanics, measure real-time particle inhalation. Cons: Need expansion for measuring nanoparticles, association with biological impact needed. | Real-time particle size distribution, inhaled particle quantity, inhalation dynamics. | HUMITIPAA to assess inhaled particle profiles (quantity and size distribution) from ECs containing VEA or menthol. |
