Gas embolism is a medical condition leading to the blockage of blood flow in the microvasculature by gas bubbles. While reported as rare, gas embolism often has devastating, fatal physiological consequences. Despite this acute importance, the genesis and evolution of air bubbles in blood vessels under different physiological conditions, such as blood viscosity and blood flow rate, is still understudied, largely because of difficult experimentation and in situ visualization. The objective of this work was to study the gas embolism phenomenon in vitro, using a microfluidic system that mimicked the architecture of microvasculature. The microfluidic systems comprised linear channels with two different air inlet types, namely, T- and Y-junctions with three different widths (20 µm, 40 µm, and 60 µm), and a 30 µm width honeycombed network with three bifurcation angles (30°, 60°, and 90°). Three synthetic liquids equivalent to 0%, 20%, and 46% hematocrit that mimicked the physiological blood viscosity and hematocrit concentrations were used. Our results show that: (i) 20 µm and 40 µm width channels had an elevated risk of gas embolism due to wide fluctuations in the total slug sizes; (ii) the resistance to the flow of air bubbles increased with the increase in the equivalent concentration of hematocrit; (iii) gas bubbles causing blockages and dampening of the flow velocity were frequently observed in 20 µm channels, and lastly (iv) increased risk of gas embolism was observed in the honeycomb architecture with 60° and 30° bifurcations. This work suggests that in vitro experimentation using microfluidic devices with microvascular tissue-like structures opens the possibility of studying this medical condition with high reproducibility and impacts the fact-based medical guidelines for preventing or mitigating iatrogenic occurrences.

Cutaneous wound healing is a complex multi-stage process involving direct and indirect cell communication events with the aim of efficiently restoring the barrier function of the skin. One key aspect in cutaneous wound healing is associated with cell movement and migration into the physically, chemically and biologically injured area resulting in wound closure. Understanding the conditions under which cell migration is impaired and elucidating the cellular and molecular mechanisms that improve healing dynamics is therefore crucial in devising novel therapeutic strategies to elevate patient suffering, reduce scaring and eliminate chronic wounds. Following the global trend towards automation, miniaturization and integration of cell-based assays into microphysiological systems, conventional wound healing assays such as the scratch assay or cell exclusion assay have recently been translated and improved using microfluidics and lab-on-a-chip technologies. These miniaturized cell analysis systems allow precise spatial and temporal control over a range of dynamic microenvironmental factors including shear stress, biochemical and oxygen gradients to create more reliable in vitro models that resemble the in vivo microenvironment of a wound more closely on a molecular, cellular, and tissue level. The current review provides (a) an overview on the main molecular and cellular processes that take place during wound healing, (b) a brief introduction into conventional in vitro wound healing assays, and (c) a perspective on future cutaneous and vascular wound healing research using microfluidic technology.