Researchers from ITMO University in Russia say they have developed artificial blood vessels that reportedly are not susceptible to blood clot formation. The achievement was made possible by a new generation of drug-containing coating applied to the inner surface of the vessel, according to the scientists whose study (“Synthesis of Thrombolytic Sol-Gel Coatings: Toward Drug-Entrapped Vascular Grafts”) was published in the Journal of Medicinal Chemistry.

Surgery, associated with cardiovascular diseases, such as ischemia, often requires the implantation of vascular grafts, which are artificial blood vessels, aimed at restoring the blood flow in a problematic part of the circulatory system. A serious disadvantage of vascular grafts is their tendency to get blocked due to clot formation, which results in compulsory and lifelong intake of anticoagulants among patients and sometimes may even require an additional surgical intervention.

In the study, a research team led by Vladimir Vinogradov, Ph.D., head of the international laboratory of solution chemistry of advanced materials and technologies at ITMO University, proposed a solution to the problem. The scientists synthesized a thin film made of densely packed aluminum oxide nanorods blended with molecules of a thrombolytic enzyme (urokinase-type plasminogen activator). Adhered to the inner surface of a vascular graft, the film causes the parietal area of the graft to get filled with a stable concentration of plasmin, which is capable of dissolving clots that form.

The properties of the film arise from its structure, which represents a porous matrix that accommodates the plasminogen activator. The matrix lets in plasminogen, a proenzyme naturally occurring in blood plasma. When plasminogen meets plasminogen activator inside the matrix, clot-dissolving plasmin forms.

Yulia Chapurina, laboratory researcher and first author of the paper, set up several in vitro experiments that helped demonstrate just how effective the film is:

“In order to test how our improved vascular graft worked, we grew an artificial clot made of blood plasma mixed with thrombin and placed it inside the graft,” noted Chapurina. “The results of the experiment amazed us. Very soon the clot started to dissolve and leak through the graft. In reality, our coating would destroy clots at the stage of formation, constantly ensuring an unobstructed blood flow in the graft.”

Latest-generation vascular grafts rely on drug-eluting technology, i.e., they release medicine into the blood. The lifetime of such grafts is often determined by the amount of drug stored within the graft, which, in essence, means that they merely postpone the formation of clots. The system, developed by the researchers, is based on the entrapment of the drug inside a porous protective shell, which makes the lifetime of such a graft practically unlimited.

“Our approach is concept-based and can be applied not only to artificial blood vessels, but to any kind of implants,” pointed out Dr. Vinogradov.” You just need to take the right kind of drug. For example, after the implantation of an artificial ureter, urease crystals often start to grow inside and doctors do not know how to deal with this problem. It is possible to apply a similar drug-containing coating that dissolves urease. The same approach may be used for kidney or liver surgery, but these are plans for the future.”

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