Drug transport from blood to extravascular tissue can locally be achieved by increasing the vascular permeability through ultrasound-activated microbubbles. However, the mechanism remains unknown, including whether short and long cycles of ultrasound induce the same onset rate, spatial distribution, and amount of vascular permeability increase. Accurate models are necessary for insights into the mechanism so a microvessel-on-a-chip is developed with a membrane-free extravascular space.
View Article and Find Full Text PDFModern drug development increasingly requires comprehensive models that can be utilized in the earliest stages of compound and target discovery. Here we report a phenotypic screening exercise in a high-throughput Organ-on-a-Chip setup. We assessed the inhibitory effect of 1537 protein kinase inhibitors in an angiogenesis assay.
View Article and Find Full Text PDFTraditionally, to quantify permeability of a biological barrier, the initial slope is used, based on the assumption of sink condition (concentration of the donor is constant, and the receiver increases less than 10%). With on-a-chip barrier models, this assumption fails in cell-free or leaky conditions, which requires the use of the exact solution. To encounter a time delay from performing the assay and acquiring the data, we present a protocol with the exact equation modified to incorporate a time offset.
View Article and Find Full Text PDFThe vasculature system plays a critical role in inflammation processes in the body. Vascular inflammatory mechanisms are characterized by disruption of blood vessel wall permeability together with increased immune cell recruitment and migration. There is a critical need to develop models that fully recapitulate changes in vascular barrier permeability in response to inflammatory conditions.
View Article and Find Full Text PDFReactive oxygen species (ROS) have different properties and biological functions. They contribute to cell signaling and, in excessive amounts, to oxidative stress (OS). Although ROS is pivotal in a wide number of physiological systems and pathophysiological processes, direct quantification in vivo is quite challenging and mainly limited to in vitro studies.
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