Cardiovascular diseases are often caused by changes in structure and function of small blood vessels. For instance, self-reported rates of hypertension suggest that the rate is increasing, says a 2003 report from the National Health and Nutrition Examination Survey. A microfluidic platform simulating the biological response of an artery could not only enable organ-based screens to occur more frequently throughout a drug development trial, but also yield a comprehensive understanding of the underlying mechanisms behind pathologic changes in small arteries and develop better treatment strategies. Axel Gunther from the University of Toronto argues that such MEMS-based devices could potentially help in the assessment of a patient's microvascular status in a clinical setting (personalized medicine).
Conventional methods used to examine intrinsic properties of isolated resistance vessels (arterioles and small arteries with diameters varying between 30 µm and 300 µm) include the pressure myography technique. However, such methods currently require manually skilled personnel and are not scalable. An artery-on-a-chip could overcome several of these limitations by accommodating an artery onto a platform which would be scalable, inexpensive and possibly automated in its manufacturing.
An organ-based microfluidic platform has been developed as a lab-on-a-chip onto which a fragile blood vessel can be fixed, allowing for determinants of resistance artery malfunctions to be studied.
The artery microenvironment is characterized by surrounding temperature, transmural pressure, and luminal & abluminal drug concentrations. The multiple inputs from a microenvironment cause a wide range of mechanical or chemical stimuli on the smooth muscle cells (SMCs) and endothelial cells (ECs) that line the vessel's outer and luminal walls, respectively. Endothelial cells are responsible for releasing vasoconstriction and vasodilator factors, thus modifying tone. Vascular tone is defined as the degree of constriction inside a blood vessel relative to its maximum diameter. Pathogenic concepts currently believe that subtle changes to this microenvironment have pronounced effects on arterial tone and can severely alter peripheral vascular resistance. The engineers behind this design believe that a specific strength lies in its ability to control and simulate heterogeneous spatiotemporal influences found within the microenvironment, whereas myography protocols have, by virtue of their design, only established homogeneous microenvironments.  They proved that by delivering phenylephrine through only one of the two channels providing superfusion to the outer walls, the drug-facing side constricted much more than the drug opposing side.
The artery-on-a-chip is designed for reversible implantation of the sample. The device contains a microchannel network, an artery loading area and a separate artery inspection area. There is a microchannel used for loading the artery segment, and when the loading well is sealed, it is also used as a perfusion channel, to replicate the process of nutritive delivery of arterial blood to a capillary bed in the biological tissue.  Another pair of microchannels serves to fix the two ends of the arterial segment. Finally, the last pair of microchannels is used to provide superfusion flow rates, in order to maintain the physiological and metabolic activity of the organ by delivering a constant sustaining medium over the abluminal wall. A thermoelectric heater and a thermoresistor are connected to the chip and maintain physiological temperatures at the artery inspection area.
The protocol of loading and securing the tissue sample into the inspection zone helps understand how this approach acknowledges whole organ functions. After immersing the tissue segment into the loading well, the loading process is driven by a syringe withdrawing a constant flow rate of buffer solution at the far end of the loading channel. This causes the transport of the artery towards its dedicated position. This is done with closed fixation and superfusion in/outlet lines. After stopping the pump, sub-atmospheric pressure is applied through one of the fixation channels. Then after sealing the loading well shut, the second fixation channel is subjected to a sub-atmospheric pressure. Now the artery is symmetrically established in the inspection area, and a transmural pressure is felt by the segment. The remaining channels are opened and constant perfusion and superfusion are adjusted using separate syringe pumps.
Vessel-on-chips have been applied to study many disease processes. For example, Alireza Mashaghi and his co-workers developed a model to study viral hemorrhagic syndrome, which involves virus induced vascular integrity loss. The model was used to study Ebola virus disease and to study anti-Ebola drugs. In 2021, the approach has been adapted to model Lassa fever and to show the therapeutic effects of peptide FX-06 for Lassa virus disease.