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It is important to clarify the transport of biomolecules and chemicals to tissues. Herein, we present an electrochemical imaging method for evaluating the endothelial permeability. In this method, the diffusion of electrochemical tracers, [Fe(CN) 6 ] 4– , through a monolayer of human umbilical vein endothelial cells (HUVECs) was monitored using a large-scale integration-based device containing 400 electrodes. In conventional tracer-based assays, tracers that diffuse through an HUVEC monolayer into another channel are detected. In contrast, the present method does not employ separated channels. In detail, a HUVEC monolayer is immersed in a solution containing [Fe(CN) 6 ] 4– on the device. As [Fe(CN) 6 ] 4– is oxidized and consumed at the packed electrodes, [Fe(CN) 6 ] 4– begins to diffuse through the monolayer from the bulk solution to the electrodes and the obtained currents depend on the endothelial permeability. As a proof-of-concept, the effects of histamine on the monolayer were monitored. Also, an HUVEC monolayer was cocultured with cancer spheroids, and the endothelial permeability was monitored to evaluate the metastasis of the cancer spheroids. Unlike conventional methods, the device can provide spatial information, allowing the interaction between the monolayer and the spheroids to be monitored. The developed method is a promising tool for organs-on-a-chip and drug screening in vitro.

Three-dimensional organs and tissues can be constructed using hydrogels as support matrices for cells. For the assembly of these gels, chemical and physical reactions that induce gluing should be induced locally in target areas without causing cell damage. Herein, we present a novel electrochemical strategy for gluing hydrogel fibers. In this strategy, a microelectrode electrochemically generated HClO or Ca2+, and these chemicals were used to crosslink chitosan–alginate fibers fabricated using interfacial polyelectrolyte complexation. Further, human umbilical vein endothelial cells were incorporated into the fibers, and two such fibers were glued together to construct “+”-shaped hydrogels. After gluing, the hydrogels were embedded in Matrigel and cultured for several days. The cells spread and proliferated along the fibers, indicating that the electrochemical glue was not toxic toward the cells. This is the first report on the use of electrochemical glue for the assembly of hydrogel pieces containing cells. Based on our results, the electrochemical gluing method has promising applications in tissue engineering and the development of organs on a chip.

Vascular form vascular organs and the walls of blood vessels play a crucial role in transporting nutritive compounds and drugs. Vascular cells also release factors required to maintain the homeostasis of the organs. Since cancer cells travel from tumors to secondary sites during metastasis through the vasculature, it is important to investigate the interactions of vascular and cancer cells. In vitro vascular models, including endothelial cell monolayers, tubular structures in three‐dimensional culture scaffolds, and microfluidic cultures, have been developed to facilitate research on drug discovery and in‐depth disease mechanisms. In addition to the common optical methods proposed for the evaluation of these models, electrochemical assays have been applied for evaluating cell activities and drug effects owing to their numerous advantages such as low invasion, real‐time detection, or high sensitivity and selectivity. The present review focuses on electrochemical assays related to vascular model structure and function. First, we summarize strategies for the electrochemical detection of nitric oxide and reactive oxygen species; assessment of endothelial cell barrier integrity using transepithelial electrical resistance measurements; endothelial permeability measurement using electrochemical tracers; evaluation of respiration activity, topography, and mRNA expression via electrochemical collection. We further discuss the methods for electrochemical cell analysis in detail, along with the variety of electrochemical systems available for these purposes, including microfluidic devices and electrochemical scanning probe microscopes. Finally, we conclude our review and propose perspectives for research that are likely to become relevant in the field.

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