A Microfluidic Model Artery for Studying the Mechanobiology of Endothelial Cells.

Recent vascular mechanobiology studies find that endothelial cells (ECs) convert multiple mechanical forces into functional responses in a nonadditive way, suggesting that signaling pathways such as those regulating cytoskeleton may be shared among the processes of converting individual forces. However, previous in vitro EC-culture platforms are inherent with extraneous mechanical components, which may saturate or insufficiently activate the shared signaling pathways and accordingly, may misguide EC mechanobiological responses being investigated. Here, a more physiologically relevant model artery is reported that accurately reproduces most of the mechanical forces found in vivo, which can be individually varied in any combination to pathological levels to achieve diseased states. Arterial geometries of normal and diseased states are also realized. By mimicking mechanical microenvironments of early-stage atherosclerosis, it is demonstrated that the elevated levels of the different types of stress experienced by ECs strongly correlate with the disruption of barrier integrity, suggesting that boundaries of an initial lesion could be sites for efficient disease progression.

Microfluidic valvular chips and a numerical lymphatic vessel model for the study of lymph transport characteristics.

Lymph transport inside lymphatic vessels is highly complex and not yet fully understood. So far, a consensus has not been reached among existing analytical models on how spatiotemporal coordination of contracting adjacent lymphangions affects lymph transport. To understand complex lymph transport, we created a novel microfluidic valvular chip with flexible bicuspid valves and segmental pneumatic pumps based on a microfluidic device with an inside 3D structure made of hydrogels. Inside the chip, water moved unidirectionally when the microfluidic channel was locally compressed, with its velocity profile closely resembling the waveform of lymph observed in vivo. Furthermore, for a systematic and mechanistic study, we constructed a numerical model based on fluid-structure interaction and validated the model via demonstration of similarities in water transport characteristics between the model and the chip. Using this model, we examined various mechanical and time-dependent parameters, such as period, phase delay, sequence, and strength of contractions, valve compliance, fluid viscosity, and pressure differences, for their effects on water transport. Although our model is simplified, it enabled a parametric study that helped clarify the mechano-temporal correlations between compressions of adjacent chambers via transmissions of hydrodynamic forces, which regulate complex lymph transport. Moreover, our chip demonstrated technical advances that enable unidirectional discrete movement of fluid in the picoliter range by phenumatic pumping. The velocity profile is also similar to the pulse waveform of arteries under pathological conditions such as increased aortic stiffness, allowing our chip to be used for in vitro mechanobiology studies of endothelial cells.

Superabsorbent Polymer Network Degradable by a Human Urinary Enzyme.

Owing to its superior water absorption capacity, superabsorbent polymer (SAP) based on a poly (acrylic acid) network is extensively used in industrial products such as diapers, wound dressing, or surgical pads. However, because SAP does not degrade naturally, a massive amount of non-degradable waste is discarded daily, posing serious environmental problems. Considering that diapers are the most widely used end-product of SAP, we created one that is degradable by a human urinary enzyme. We chose three enzyme candidates, all of which have substrates that were modified with polymerizable groups to be examined for cleavable crosslinkers of SAP. We found that the urokinase-type plasminogen activator (uPA) substrate, end-modified with acrylamide groups at sufficient distances from the enzymatic cleavage site, can be successfully used as a cleavable crosslinker of SAP. The resulting SAP slowly degraded over several days in the aqueous solution containing uPA at a physiological concentration found in human urine and became shapeless in ~30 days.