Prey Capturing Dynamics and Nanomechanically Graded Cutting Apparatus of Dragonfly Nymph.

Aquatic predatory insects, like the nymphs of a dragonfly, use rapid movements to catch their prey and it presents challenges in terms of movements due to drag forces. Dragonfly nymphs are known to be voracious predators with structures and movements that are yet to be fully understood. Thus, we examine two main mouthparts of the dragonfly nymph (Libellulidae: Insecta: Odonata) that are used in prey capturing and cutting the prey. To observe and analyze the preying mechanism under water, we used high-speed photography and, electron microscopy. The morphological details suggest that the prey-capturing labium is a complex grasping mechanism with additional sensory organs that serve some functionality. The time taken for the protraction and retraction of labium during prey capture was estimated to be 187 ± 54 ms, suggesting that these nymphs have a rapid prey mechanism. The Young's modulus and hardness of the mandibles were estimated to be 9.1 ± 1.9 GPa and 0.85 ± 0.13 GPa, respectively. Such mechanical properties of the mandibles make them hard tools that can cut into the exoskeleton of the prey and also resistant to wear. Thus, studying such mechanisms with their sensory capabilities provides a unique opportunity to design and develop bioinspired underwater deployable mechanisms.

In silico optimization of targeted aerosol delivery in upper airways via Inhaled Volume Tracking.

BACKGROUND: Despite the widespread use of aerosol inhalation as a drug delivery method, targeted delivery to the upper airways remains an ongoing challenge in the quest for improved clinical response in respiratory disease. METHODS: Here, we examine in silico flow and particle dynamics when using an oral Inhaled Volume Tracking manoeuvre. A short pulsed aerosol bolus is injected during slow inhalation flow rates followed by clean air, and a breath-hold is initiated once it reaches the desired depth. We explore the fate of a broad particle size range (1-40 µm) for both upright and supine positions. FINDINGS: Our findings illustrate that despite attempts to mitigate dispersion using slower flow rates, the laryngeal jet disperses the aerosol bolus and thus remains a hurdle for efficient targeted delivery. Nevertheless, we show a decrease in extra-thoracic deposition; large aerosols in the range of 10-30 µm potentially outperform existing inhalation methods, showing deposition fractions of up to 80% in an upright orientation. INTERPRETATION: The improved deposition during Inhaled Volume Tracking shows promise for clinical applications and could be leveraged to deliver larger payloads to the upper airways.

In situ-Like Aerosol Inhalation Exposure for Cytotoxicity Assessment Using Airway-on-Chips Platforms.

Lung exposure to inhaled particulate matter (PM) is known to injure the airway epithelium via inflammation, a phenomenon linked to increased levels of global morbidity and mortality. To evaluate physiological outcomes following PM exposure and concurrently circumvent the use of animal experiments, in vitro approaches have typically relied on traditional assays with plates or well inserts. Yet, these manifest drawbacks including the inability to capture physiological inhalation conditions and aerosol deposition characteristics relative to in vivo human conditions. Here, we present a novel airway-on-chip exposure platform that emulates the epithelium of human bronchial airways with critical cellular barrier functions at an air-liquid interface (ALI). As a proof-of-concept for in vitro lung cytotoxicity testing, we recapitulate a well-characterized cell apoptosis pathway, induced through exposure to 2 µm airborne particles coated with αVR1 antibody that leads to significant loss in cell viability across the recapitulated airway epithelium. Notably, our in vitro inhalation assays enable simultaneous aerosol exposure across multiple airway chips integrated within a larger bronchial airway tree model, under physiological respiratory airflow conditions. Our findings underscore in situ-like aerosol deposition outcomes where patterns depend on respiratory flows across the airway tree geometry and gravitational orientation, as corroborated by concurrent numerical simulations. Our airway-on-chips not only highlight the prospect of realistic in vitro exposure assays in recapitulating characteristic local in vivo deposition outcomes, such platforms open opportunities toward advanced in vitro exposure assays for preclinical cytotoxicity and drug screening applications.

In Silico Optimization of Fiber-Shaped Aerosols in Inhalation Therapy for Augmented Targeting and Deposition across the Respiratory Tract.

Motivated by a desire to uncover new opportunities for designing the size and shape of fiber-shaped aerosols towards improved pulmonary drug delivery deposition outcomes, we explore the transport and deposition characteristics of fibers under physiologically inspired inhalation conditions in silico, mimicking a dry powder inhaler (DPI) maneuver in adult lung models. Here, using computational fluid dynamics (CFD) simulations, we resolve the transient translational and rotational motion of inhaled micron-sized ellipsoid particles under the influence of aerodynamic (i.e., drag, lift) and gravitational forces in a respiratory tract model spanning the first seven bifurcating generations (i.e., from the mouth to upper airways), coupled to a more distal airway model representing nine generations of the mid-bronchial tree. Aerosol deposition efficiencies are quantified as a function of the equivalent diameter (dp) and geometrical aspect ratio (AR), and these are compared to outcomes with traditional spherical particles of equivalent mass. Our results help elucidate how deposition patterns are intimately coupled to dp and AR, whereby high AR fibers in the narrow range of dp = 6-7 µm yield the highest deposition efficiency for targeting the upper- and mid-bronchi, whereas fibers in the range of dp= 4-6 µm are anticipated to cross through the conducting regions and reach the deeper lung regions. Our efforts underscore previously uncovered opportunities to design the shape and size of fiber-like aerosols towards targeted pulmonary drug delivery with increased deposition efficiencies, in particular by leveraging their large payloads for deep lung deposition.

In silico approaches to respiratory nasal flows: A review.

The engineering discipline of in silico fluid dynamics delivers quantitative information on airflow behaviour in the nasal regions with unprecedented detail, often beyond the reach of traditional experiments. The ability to provide visualisation and analysis of flow properties such as velocity and pressure fields, as well as wall shear stress, dynamically during the respiratory cycle may give significant insight to clinicians. Yet, there remains ongoing challenges to advance the state-of-the-art further, including for example the lack of comprehensive CFD modelling on varied cohorts of patients. The present article embodies a review of previous and current in silico approaches to simulating nasal airflows. The review discusses specific modelling techniques required to accommodate physiologically- and clinically-relevant findings. It also provides a critical summary of the reported results in the literature followed by an outlook on the challenges and topics anticipated to drive research into the future.

Targeting inhaled aerosol delivery to upper airways in children: Insight from computational fluid dynamics (CFD).

Despite the prevalence of inhalation therapy in the treatment of pediatric respiratory disorders, most prominently asthma, the fraction of inhaled drugs reaching the lungs for maximal efficacy remains adversely low. By and large drug delivery devices and their inhalation guidelines are typically derived from adult studies with child dosages adapted according to body weight. While it has long been recognized that physiological (e.g. airway sizes, breathing maneuvers) and physical transport (e.g. aerosol dynamics) characteristics are critical in governing deposition outcomes, such knowledge has yet to be extensively adapted to younger populations. Motivated by such shortcomings, the present work leverages in a first step in silico computational fluid dynamics (CFD) to explore opportunities for augmenting aerosol deposition in children based on respiratory physiological and physical transport determinants. Using an idealized, anatomically-faithful upper airway geometry, airflow and aerosol motion are simulated as a function of age, spanning a five year old to an adult. Breathing conditions mimic realistic age-specific inhalation maneuvers representative of Dry Powder Inhalers (DPI) and nebulizer inhalation. Our findings point to the existence of a single dimensionless curve governing deposition in the conductive airways via the dimensionless Stokes number (Stk). Most significantly, we uncover the existence of a distinct deposition peak irrespective of age. For the DPI simulations, this peak (∼ 80%) occurs at Stk ≈ 0.06 whereas for nebulizer simulations, the corresponding peak (∼ 45%) occurs in the range of Stk between 0.03-0.04. Such dimensionless findings hence translate to an optimal window of micron-sized aerosols that evolves with age and varies with inhalation device. The existence of such deposition optima advocates revisiting design guidelines for optimizing deposition outcomes in pediatric inhalation therapy.