A 3D tissue-engineered airway model for the assessment of epithelial responses to novel nanotherapeutics

Recent studies showed that nasal high flow (NHF) with or without supplemental oxygen can assist ventilation of patients with chronic respiratory and sleep disorders. The hypothesis of this study was to test whether NHF can clear dead space in two different models of the upper nasal airways. The first was a simple tube model consisting of a nozzle to simulate the nasal valve area, connected to a cylindrical tube to simulate the nasal cavity. The second was a more complex anatomically representative upper airway model, constructed from segmented CT-scan images of a healthy volunteer. After filling the models with tracer gases, NHF was delivered at rates of 15, 30, and 45 l/min. The tracer gas clearance was determined using dynamic infrared CO2 spectroscopy and 81mKr-gas radioactive gamma camera imaging. There was a similar tracer-gas clearance characteristic in the tube model and the upper airway model: clearance half-times were below 1.0 s and decreased with increasing NHF rates. For both models, the anterior compartments demonstrated faster clearance levels (half-times < 0.5 s) and the posterior sections showed slower clearance (half-times < 1.0 s). Both imaging methods showed similar flow-dependent tracer-gas clearance in the models. For the anatomically based model, there was complete tracer-gas removal from the nasal cavities within 1.0 s. The level of clearance in the nasal cavities increased by 1.8 ml/s for every 1.0 l/min increase in the rate of NHF. The study has demonstrated the fast-occurring clearance of nasal cavities by NHF therapy, which is capable of reducing of dead space rebreathing.

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Application value of 3D printing airway model in clinical management of difficult airway

Minerva Medica ◽

10.23736/s0026-4806.21.07724-7 ◽

2021 ◽

Author(s):

Jimin WU ◽

Peiyi MEI ◽

Yini WU ◽

Linfei JIN ◽

Qiaomin XU ◽

...

Keyword(s):

3D Printing ◽

Difficult Airway ◽

Clinical Management ◽

Airway Model

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Establishment and characterization of an in vitro human small airway model (SmallAir™)

European Journal of Pharmaceutics and Biopharmaceutics ◽

10.1016/j.ejpb.2016.12.006 ◽

2017 ◽

Vol 118 ◽

pp. 68-72 ◽

Cited By ~ 19

Author(s):

Song Huang ◽

Bernadett Boda ◽

Jimmy Vernaz ◽

Emilie Ferreira ◽

Ludovic Wiszniewski ◽

...

Keyword(s):

Small Airway ◽

Airway Model

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Dynamics of Liquid Plugs of Buffer and Surfactant Solutions in a Micro-Engineered Pulmonary Airway Model

Langmuir ◽

10.1021/la903038a ◽

2010 ◽

Vol 26 (5) ◽

pp. 3744-3752 ◽

Cited By ~ 29

Author(s):

Hossein Tavana ◽

Chuan-Hsien Kuo ◽

Qian Yi Lee ◽

Bobak Mosadegh ◽

Dongeun Huh ◽

...

Keyword(s):

Surfactant Solutions ◽

Pulmonary Airway ◽

Airway Model

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Airway pressures in an asymmetrically branched airway model of the dog respiratory system

Journal of Applied Physiology ◽

10.1152/jappl.1984.57.4.1222 ◽

1984 ◽

Vol 57 (4) ◽

pp. 1222-1230 ◽

Cited By ~ 8

Author(s):

Andrew C. Jackson ◽

Mehrdad Tabrizi ◽

Michael I. Kotlikoff ◽

Jon R. Voss

Keyword(s):

Respiratory System ◽

High Frequency ◽

High Frequency Ventilation ◽

Tissue Properties ◽

Pressure Distributions ◽

Lumped Parameter ◽

Airway Opening ◽

Frequency Ventilation ◽

Lung Periphery ◽

Airway Model

A computer model of the mechanical properties of the dog respiratory system based on the asymmetrically branching airway model of Horsfield et al. (11) is described. The peripheral ends of this airway model were terminated by a lumped-parameter impedance representing gas compression in the alveoli, and lung and chest wall tissue properties were derived from measurements made in this laboratory. Using this model we predicted the respiratory system impedance and the distribution of pressures along the airways in the dog lung. Predicted total respiratory system impedances for frequencies between 4 and 64 Hz at three lung volumes were found to compare quite closely to measured impedances in dogs. Serial pressure distributions were found to be frequency-dependent and to result in higher pressures in the lung periphery than at the airway opening at some frequencies. The implications of this fading for high-frequency ventilation are discussed. impedance; high-frequency ventilation; central airway resistance; respiratory system resistance; airway pressure distribution; distribution of ventilation Submitted on November 14, 1983 Accepted on May 8, 1984

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Effect of vitamin D3 on lung damage induced by cigarette smoke in mice

Open Medicine ◽

10.1515/med-2019-0096 ◽

2019 ◽

Vol 14 (1) ◽

pp. 827-832

Author(s):

Xin Zheng ◽

Nini Qu ◽

Lina Wang ◽

Guoli Wang ◽

Rui Jiao ◽

...

Keyword(s):

Cigarette Smoking ◽

Cigarette Smoke ◽

Vitamin D3 ◽

Lung Diseases ◽

Low Dose ◽

Lung Damage ◽

Over Expression ◽

Ifn Γ ◽

Airway Model ◽

Morphological Assessment

AbstractCigarette smoking is known to induce serious lung diseases, but there is not an effective method to solve this problem. The present study investigated vitamin D3 on over-expression of CXCR3 and CXCL10 in mice induced by cigarette smoking. A pulmonary airway model was designed, and morphological assessment of emphysema, IL-4, IFN-γ and CXCL10 concentration in bronchoalveolar lavage fluids, expression of CXCR3 and CXCL10 were detected. Emphysema of the mice only exposed to cigarette smoke was significant, and concentration of IL-4, IFN-γ and CXCL10 was also increased. In addition, CXCR3 and CXCL10 were over-expressed. The degree of emphysema, concentration of IL-4, IFN-γ and CXCL10, and expression of CXCR3 and CXCL10 in mice administrated with low dose vitamin D3 were similar to the normally treated mice. Low dose of vitamin D3 can effectively protect the lung from the damage induced by cigarette smoke.

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Distinct Mucoinflammatory Phenotype and the Immunomodulatory Long Noncoding Transcripts Associated with SARS-CoV-2 Airway Infection

10.1101/2021.05.13.21257152 ◽

2021 ◽

Author(s):

Dinesh Devadoss ◽

Arpan Acharya ◽

Marko Manevski ◽

Kabita Pandey ◽

Glen M Borchert ◽

...

Keyword(s):

Nasopharyngeal Swab ◽

Differential Modulation ◽

Primary Target ◽

Respiratory Epithelial Cells ◽

Tissue Model ◽

Cell Responses ◽

Elevated Expression ◽

Respiratory Epithelial ◽

Airway Model ◽

Dual Staining

Respiratory epithelial cells are the primary target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated the 3D human airway tissue model to evaluate innate epithelial cell responses to SARS-CoV-2 infection. A SARS-CoV-2 clinical isolate productively infected the 3D-airway model with a time-dependent increase in viral load (VL) and concurrent upregulation of airway immunomodulatory factors (IL-6, ICAM-1, and SCGB1A1) and respiratory mucins (MUC5AC, MUC5B, MUC2, and MUC4), and differential modulation of select long noncoding RNAs (lncRNAs i.e., LASI, TOSL, NEAT1, and MALAT1). Next, we examined these immunomodulators in the COVID-19 patient nasopharyngeal swab samples collected from subjects with high- or low-VLs (~100-fold difference). As compared to low-VL, high-VL patients had prominent mucoinflammatory signature with elevated expression of IL-6, ICAM-1, SCGB1A1, SPDEF, MUC5AC, MUC5B, and MUC4. Interestingly, LASI, TOSL, and NEAT1 lncRNA expressions were also markedly elevated in high-VL patients with no change in MALAT1 expression. In addition, dual-staining of LASI and SARS-CoV-2 nucleocapsid N1 RNA showed predominantly nuclear/perinuclear localization at 24 hpi in 3D-airway model as well as in high-VL COVID-19 patient nasopharyngeal cells, which exhibited high MUC5AC immunopositivity. Collectively, these findings suggest SARS-CoV-2 induced lncRNAs may play a role in acute mucoinflammatory response observed in symptomatic COVID-19 patients.

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