Clot Accumulation in 3D Microfluidic Bifurcating Microvasculature Network.

The microvasculature, which makes up the majority of the cardiovascular system, plays a crucial role in the process of thrombosis, with the pathological formation of blood clots inside blood vessels. Since blood microflow conditions significantly influence platelet activation and thrombosis, accurately mimicking the structure of bifurcating microvascular networks and emulating local physiological blood flow conditions are valuable for understanding blood clot formation. In this work, we present an in vitro model for blood clotting in microvessels, focusing on 3D bifurcations that align with Murray's law, which guides vascular networks by maintaining a constant wall shear rate throughout.

A double-edged sword: The complex interplay between engineered nanoparticles and platelets.

Nanoparticles (NP) play a crucial role in nanomedicine, serving as carriers for localized therapeutics to allow for precise drug delivery to specific disease sites and conditions. When injected systemically, NP can directly interact with various blood cell types, most critically with circulating platelets. Hence, the potential activation/inhibition of platelets following NP exposure must be evaluated a priori due to possible debilitating outcomes.

A Fibrin-Thrombin Based In Vitro Perfusion System to Study Flow-Related Prosthetic Heart Valves Thrombosis.

Prosthetic heart valve (PHV) replacement has increased the survival rate and quality of life for heart valve-diseased patients. However, PHV thrombosis remains a critical problem associated with these procedures. To better understand the PHV flow-related thrombosis problem, appropriate experimental models need to be developed.

Exploring the role of electrostatic deposition on inhaled aerosols in alveolated microchannels.

Large amounts of net electrical charge are known to accumulate on inhaled aerosols during their generation using commonly-available inhalers. This effect often leads to superfluous deposition in the extra-thoracic airways at the cost of more efficient inhalation therapy. Since the electrostatic force is inversely proportional to the square of the distance between an aerosol and the airway wall, its role has long been recognized as potentially significant in the deep lungs.

A Novel Trans-Tracheostomal Retrograde Inhalation Technique Increases Subglottic Drug Deposition Compared to Traditional Trans-Oral Inhalation.

Subglottic stenosis represents a challenging clinical condition in otolaryngology. Although patients often experience improvement following endoscopic surgery, recurrence rates remain high. Pursuing measures to maintain surgical results and prevent recurrence is thus necessary.

In vitro-in silico correlation of three-dimensional turbulent flows in an idealized mouth-throat model.

There exists an ongoing need to improve the validity and accuracy of computational fluid dynamics (CFD) simulations of turbulent airflows in the extra-thoracic and upper airways. Yet, a knowledge gap remains in providing experimentally-resolved 3D flow benchmarks with sufficient data density and completeness for useful comparison with widely-employed numerical schemes. Motivated by such shortcomings, the present work details to the best of our knowledge the first attempt to deliver in vitro-in silico correlations of 3D respiratory airflows in a generalized mouth-throat model and thereby assess the performance of Large Eddy Simulations (LES) and Reynolds-Averaged Numerical Simulations (RANS).

Exploring pulmonary distribution of intratracheally instilled liquid foams in excised porcine lungs.

The applicability of inhalation therapy to some severe pulmonary conditions is often compromised by limited delivery rates (i.e. total dose) and low deposition efficiencies in the respiratory tract, most notably in the deep pulmonary acinar airways.

PEG-fibrinogen hydrogel microspheres as a scaffold for therapeutic delivery of immune cells.

Recent advances in the field of cell therapy have proposed new solutions for tissue repair and regeneration using various cell delivery approaches. Here we studied a novel topical delivery system of encapsulated cells in hybrid polyethylene glycol-fibrinogen (PEG-Fb) hydrogel microspheres to respiratory tract models. We investigated basic parameters of cell encapsulation, delivery and release in conditions of inflamed and damaged lungs of bacterial-infected mice.

Shear thinning effect on liquid foam distribution in heterogeneously constricted in vitro airway models.

Treating diseased lung regions using inhalation therapy is often limited due to airway constrictions and obstructions that significantly reduce aerosol deposition efficiency. Intratracheal administration of liquid foams is a potential strategy to improve pulmonary drug delivery to these affected airway regions. Here, we use effective viscosity measurements and in vitro small-airway models to examine how shear thinning effects in the foam can be leveraged to achieve a more uniform distribution within heterogeneously constricted or partially obstructed airways.

Ventilation-induced epithelial injury drives biological onset of lung trauma in vitro and is mitigated with prophylactic anti-inflammatory therapeutics.

Mortality rates among patients suffering from acute respiratory failure remain perplexingly high despite the maintenance of blood oxygen homeostasis during ventilatory support. The biotrauma hypothesis advocates that mechanical forces from invasive ventilation trigger immunological mediators that spread systemically. Yet, how these forces elicit an immune response remains unclear.

Micro-particle entrapment dynamics in microfluidic pulmonary capillary networks.

The journey of vascular targeted carriers (VTC) in the circulatory system is highly intricate and includes navigation through different vessel structures, such as the vast pulmonary capillary network (PCN) in the lungs where particles can get entrapped and lead to blockage. Here, we leverage microfluidic PCN models to explore, for the first time, micro-particle capillary entrapment, in a well-controlled biophysical environment mimicking human physiological hemodynamics at true scale. This in vitro strategy mimics the challenges of vascular carrier transport during their journey in the smallest capillaries of the body (∼5 µm).

Fate of inhaled aerosols under the influence of glottal motion in a realistic in silico human tracheobronchial tree model.

Despite the prevalence of inhalation therapy in the treatment of various respiratory diseases, predicting and optimizing lung deposition fractions of inhaled drugs for maximal efficacy remains challenging due to the complex anatomical structures of the extra-thoracic airways, notably the glottal region. One of the widespread speculations in current insilico simulations lies in assuming a static glottis during inhalation, while in reality inhalation leads to significant glottis cross-sectional area expansion. The present work attempts to explore, insilico, the influence of transient movement of the glottal structures on inhalation therapy outcomes.

Human Multi-Compartment Platform for Emulating Respiratory Airborne Transmission: From Nose to Pulmonary Acini.

The past decade has witnessed tremendous endeavors to deliver novel preclinical lung models for pulmonary research endpoints, including foremost with the advent of and . With growing interest in aerosol transmission and infection of respiratory viruses within a host, most notably the SARS-CoV-2 virus amidst the global COVID-19 pandemic, the importance of crosstalk between the different lung regions (i.e.

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

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.

PerfuPul-A Versatile Perfusable Platform to Assess Permeability and Barrier Function of Air Exposed Pulmonary Epithelia.

Complex models, especially those based on human cells and tissues, may successfully reduce or even replace animal models within pre-clinical development of orally inhaled drug products. Microfluidic lung-on-chips are regarded as especially promising models since they allow the culture of lung specific cell types under physiological stimuli including perfusion and air-liquid interface (ALI) conditions within a precisely controlled environment. Currently, though, such models are not available to a broad user community given their need for sophisticated microfabrication techniques.

Airborne transmission of respiratory viruses.

The COVID-19 pandemic has revealed critical knowledge gaps in our understanding of and a need to update the traditional view of transmission pathways for respiratory viruses. The long-standing definitions of droplet and airborne transmission do not account for the mechanisms by which virus-laden respiratory droplets and aerosols travel through the air and lead to infection. In this Review, we discuss current evidence regarding the transmission of respiratory viruses by aerosols-how they are generated, transported, and deposited, as well as the factors affecting the relative contributions of droplet-spray deposition versus aerosol inhalation as modes of transmission.

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

Liquid plug therapies are commonly instilled in premature babies suffering from infant respiratory distress syndrome (IRDS) by a procedure called surfactant replacement therapy (SRT) in which a surfactant-laden bolus is instilled endotracheally in the neonatal lungs, dramatically reducing mortality and morbidity in neonatal populations. Since data are frequently limited, the optimal method for surfactant delivery has yet to be established towards more standardized guidelines. Here, we explore the dynamics of liquid plug transport using an anatomically-relevant, true-scale in vitro 3D model of the upper airways of a premature infant.

Circulating Wnt Ligands Activate the Wnt Signaling Pathway in Mature Erythrocytes.

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Focused targeting of inhaled magnetic aerosols in reconstructed in vitro airway models.

The pulmonary tract is an attractive route for topical treatments of lung diseases. Yet, our ability to confine the deposition of inhalation aerosols to specific lung regions, or local airways, remains still widely beyond reach. It has been hypothesized that by coupling magnetic particles to inhaled therapeutics the ability to locally target airway sites can be substantially improved.