Stent implantations have been used for the treatment of coronary artery disease and various methods for preventing restenosis have been developed since then. In particular, drug-eluting stents (DES) have significantly inhibited neointimal hyperplasia of a vessel and reduced the incidence of restenosis compared to bare metal stents. On the other hand, there have been recent reports that drug-eluting stents have a higher incidence of stent thrombosis than bare metal stents. Stent thrombosis is a dangerous complication that is acute and fatal even if the rate of incidence is relatively low. In addition, it is very difficult to predict the time of onset after stenting. The precise mechanism of stent thrombosis due to drug-eluting stents has not been established. However, the main reason for stent thrombosis is that the drug released from the stent slows down the process of covering blood vessels with endothelial cells, resulting in platelet activation and acute thrombosis by the coagulation proteins of the exposed blood vessels.
Stent thrombosis is most commonly seen within 30 days after coronary stenting. Patients currently undergoing stenting are receiving antiplatelet agents for one week to prevent stent thrombosis.
However, despite the risk of acute stent thrombosis, there is little research on thrombus formation on the surface of the stent. Previous studies have evaluated the drug used in drug-eluting stents and have not paid attention to the hematological changes of the surface due to stent chemical structure.
Herein, an analytic tool to study the mechanism between pharmacokinetics and dynamics on the surface of DES is required. Thus, we propose the QCN-D sensor as a potential tool for anticipating the efficacy of medications of DES, as well as the risk of restenosis. This study was designed to investigate the mechanism of stent thrombosis and to find optimal conditions for minimizing platelet attachment by observing platelet adhesion and coagulation behaviors on various surfaces in real time using the QCN-D system. The QCN-D system is capable of simultaneously providing information on the mass and viscoelasticity of the adsorbed material in real time, making it suitable for revealing how the characteristics of the surfaces are related to stent thrombosis.
First, to investigate the accuracy of the developed QCN-D sensor, standardized glycerol with varied concentrations were tested. Afterward,
we also evaluated the blood coagulation dynamics on a gold surface, a bare quartz crystal, a nitinol surface, which is the most common material of coronary stents, as well as heparin and thrombin coated gold quartzes. Finally, the QCN-D sensor was used to observe the initial blood coagulation at the DES surface using a well-known drug. Each surface was evaluated by the following factors:
(1) Onset time of coagulation; (2) velocity of fibrin attachment; (3) viscoelasticity of surfaces or dissipation; and (4) mass of the material attached on the surfaces, or frequency.
The results proved that the chemical structure of the surface has a significant impact on blood coagulation and that the developed QCN-D system is a device that can simulate blood clotting on a real stent. Thus, this QCN-D system will enable the initial assessment of the biocompatibility and haemocompatibility of biomaterials. Furthermore, it can be used to discover the mechanism of thrombosis in regards to DES and the condition of optimal anti-thrombosis that can inhibit restenosis.