Towards homogenization of liquid plug distribution in reconstructed 3D upper airways of the preterm infant

Elias-Kirma, Shani; Artzy‐Schnirman, Arbel; Sabatan, Hadas; Dabush, Chelli; Waisman, Dan; Sznitman, Josué

doi:10.1016/j.jbiomech.2021.110458

Cited by 3 publications

(2 citation statements)

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“…), with end points geared for example at pharmaco-kinetics and dynamics. In parallel, guaranteeing a hydrophilic environment is also critical when considering in vitro models for the transport of liquid plugs along the airway lumen; for such physiological scenarios, surface tension dynamics arising at the triple gas–liquid–liquid interface (i.e., air–liquid plug-lumen) must be adequately reproduced. − …”

Section: Alveolar Distensions During Breathing: Mimicking Wall Motion...mentioning

confidence: 99%

“…Transport phenomena relevant to the thin liquid lining layer covering the luminal surface of the acinar airways are discussed elsewhere, − with extensive details on its composition and characteristics. , We recall that under normal physiological conditions, the thickness of the surfactant-rich alveolar liquid lining layer is a mere 0.1–0.2 μm and is thereby over 3 orders of magnitude smaller than the typical acinar airway dimensions. Hence, dynamic interactions that may arise between the air and liquid phase (i.e., as a resultant of boundary conditions at the fluid–fluid interface) are acknowledged to become most significant with the formation of liquid plugs ,, that fill the entire luminal space under diseased conditions (e.g., chronic obstructive pulmonary disease, cystic fibrosis, Acute Respiratory Distress Syndrome) or alternatively during surfactant replacement therapy , (SRT) and related liquid-based ventilation maneuvers. While beyond the scope of the present review, we simply comment that the past decade has witnessed important microfluidic-based efforts to investigate the propagation dynamics and rupture of liquid plugs , (including mucus plugs) in models of both single airways and bifurcating trees, ,− including the role of elevated wall shear stresses (WSS) toward epithelial cell wounding and damage. ,, …”

Section: Fundamentals Of Respiratory Airflows In the Deep Lungsmentioning

confidence: 99%

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Revisiting Airflow and Aerosol Transport Phenomena in the Deep Lungs with Microfluidics

Sznitman

2021

Chem. Rev.

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The dynamics of respiratory airflows and the associated transport mechanisms of inhaled aerosols characteristic of the deep regions of the lungs are of broad interest in assessing both respiratory health risks and inhalation therapy outcomes. In the present review, we present a comprehensive discussion of our current understanding of airflow and aerosol transport phenomena that take place within the unique and complex anatomical environment of the deep lungs, characterized by submillimeter 3D alveolated airspaces and nominally slow resident airflows, known as low-Reynolds-number flows. We exemplify the advances brought forward by experimental efforts, in conjunction with numerical simulations, to revisit past mechanistic theories of respiratory airflow and particle transport in the distal acinar regions. Most significantly, we highlight how microfluidic-based platforms spanning the past decade have accelerated opportunities to deliver anatomically inspired in vitro solutions that capture with sufficient realism and accuracy the leading mechanisms governing both respiratory airflow and aerosol transport at true scale. Despite ongoing challenges and limitations with microfabrication techniques, the efforts witnessed in recent years have provided previously unattainable in vitro quantifications on the local transport properties in the deep pulmonary acinar airways. These may ultimately provide new opportunities to explore improved strategies of inhaled drug delivery to the deep acinar regions by investigating further the mechanistic interactions between airborne particulate carriers and respiratory airflows at the pulmonary microscales.

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Section: Alveolar Distensions During Breathing: Mimicking Wall Motion...mentioning

confidence: 99%

Section: Fundamentals Of Respiratory Airflows In the Deep Lungsmentioning

confidence: 99%

Revisiting Airflow and Aerosol Transport Phenomena in the Deep Lungs with Microfluidics

Sznitman

2021

Chem. Rev.

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Additive manufacturing in respiratory sciences – Current applications and future prospects

Bock

Rades

Scherließ

2022

Advanced Drug Delivery Reviews

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Design and fabrication of a three-dimensional asymmetric neonate lung model to study surfactant transport in airways

Combs,

Heiss,

Beaty

et al. 2024

Innov. Emerg. Technol.

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Neonatal respiratory distress syndrome is a potentially life-threatening condition that is often treated with the delivery of exogenous surfactants through a process called surfactant replacement therapy. This therapy includes the administration of the liquid surfactant through an endotracheal tube and mechanical ventilation. Due to the difficulty of imaging neonate lungs during this therapy, the success of surfactant delivery is often determined by observational techniques and evaluation of blood oxygen levels. The limitation of imaging creates challenges in evaluating the distribution of surfactant in airways. To address this limitation, we designed a computational, eight-generation, asymmetric neonate lung model using morphometric data to mimic the geometric structure of the human airway tree and fabricated it using an additive manufacturing technique. We used our model to study two-aliquot delivery of a clinically rated liquid surfactant under two different orientations to evaluate its distribution in airways. Our study offers a complex lung airway tree design that mimics the native geometry of the human airway tree to enable studies of therapeutics transport in airways.

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Towards homogenization of liquid plug distribution in reconstructed 3D upper airways of the preterm infant

Cited by 3 publications

References 43 publications

Revisiting Airflow and Aerosol Transport Phenomena in the Deep Lungs with Microfluidics

Revisiting Airflow and Aerosol Transport Phenomena in the Deep Lungs with Microfluidics

Additive manufacturing in respiratory sciences – Current applications and future prospects

Design and fabrication of a three-dimensional asymmetric neonate lung model to study surfactant transport in airways

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