Engineered modular microphysiological models of the human airway clearance phenomena

Abstract

Mucociliary clearance is a crucial mechanism that supports the elimination of inhaled particles, bacteria, pollution, and hazardous agents from the human airways, and it also limits the diffusion of aerosolized drugs into the airway epithelium. In spite of its relevance, few in vitro models sufficiently address the cumulative effect of the steric and interactive barrier function of mucus on the one hand, and the dynamic mucus transport imposed by ciliary mucus propulsion on the other hand. Here, ad hoc mucus models of physiological and pathological mucus are combined with magnetic artificial cilia to model mucociliary transport in both physiological and pathological states. The modular concept adopted in this study enables the development of mucociliary clearance models with high versatility since these can be easily modified to reproduce phenomena characteristic of healthy and diseased human airways while allowing to determine the effect of each parameter and/or structure separately on the overall mucociliary transport. These modular airway models can be available off‐the‐shelf because they are exclusively made of readily available materials, thus ensuring reproducibility across different laboratories.

Heterogeneity governs 3D-cultures of clinically relevant microbial communities

“…28 As CF mucus characteristics vary, not only between patients, but also within a single patient in a short period of time, [29][30][31][32][33] the concentration of Ca 2+ ions was varied to produce CF-Mu 3 Gel with viscoelastic properties (Supplementary Fig. 1a and b) tailorable to the desired stiffness according to disease progression 34 or even patient-speci c to support personalised pharmacological treatment. The average mesh size, estimated for all tested CF-Mu 3 Gel formulations, was similar independently of the composition.…”

“…(w/v) porcine stomach type III mucin (Sigma-Aldrich, M1778; lot# SLBQ7188V, Germany) and 0.71% (wt/vol) sodium chloride that falls within the ranges previously determined in CF sputum, 26,27 produced in MHB, LBB or in 7.07mg/ml NaCl exploiting the licensed technology of Bac 3 Gel, Lda, Portugal. 34 Brie y, G-CF-Mu 3 Gel® was produced through controlled diffusion of different concentrations of Ca 2+ ions ranging from 0.12-1.20% (w/v) to a mucin-based precursor solution leading to the generation of 3D structures with spatial gradients.…”

Microscopic artificial cilia – a review

“…An in vitro microphysiological model based on artificial cilia, mimicking the structure and dynamics of the human mucociliary clearance apparatus could not only help understand this process, but could also be used to test potential treatments for individuals in which this process is impaired. A first model has been demonstrated, 210 but this is still based on relatively large artificial cilia, and the challenge here is to shrink these to physiological dimensions and to include the layered structure of fluid representing the mucus film. A similar approach could be used to understand the clearance function of motile cilia present in the middle ear.…”

Microfluidic Applications of Artificial Cilia: Recent Progress, Demonstration, and Future Perspectives

“…By changing the acoustic-electric field, both transporting and trapping beads in the aqueous medium were achieved by the same microarchitecture of the ciliary band. Pacheco et al [ 188 ] proposed a study where the modular materials such as L-Mu 3 Gel and CF-Mu 3 Gel, equivalent to the physiological and CF mucus, respectively, were transported successfully with the magnetic artificial cilia. The artificial mucus models L-Mu 3 Gel and CF-Mu 3 Gel can be created using readily available materials.…”

“…As a milestone in the viscoelastic particle transportation by artificial cilia, physiological and pathological mucus were modeled using L-Mu 3 Gel and CF-Mu 3 Gel and achieved transportation in the respiratory airway model by artificial cilia. The figure was reproduced with permission from [ 188 ], published by John Wiley and Sons, 2021.…”