The enlarged section shows
the drug-loaded film that
coats the inside of the graft.
Image courtesy of ITMO
University/Yulia Chapurina
Researchers say they have developed a vascular graft that may be able to resist thrombosis indefinitely.
The team found they could trap urokinase-type plasminogen activator inside a porous, alumina sol–gel film, and this film retained its thrombolytic activity when applied to a polymer vascular graft.
Vladimir Vinogradov, PhD, of ITMO University in St. Petersburg, Russia, and his colleagues described this work in the Journal of Medicinal Chemistry.
The team synthesized a thin film made of densely packed aluminum oxide nanorods blended with molecules of the thrombolytic enzyme urokinase-type plasminogen activator.
When adhered to the inner surface of a polymer vascular graft, the film causes the parietal area of the graft to fill with a stable concentration of plasmin, which is capable of dissolving any clots that appear.
The researchers said the unique properties of the film arise from its structure, which represents a porous matrix, accommodating the plasminogen activator.
The matrix protects the plasminogen activator from the aggressive environment of the organism while also preserving the enzyme’s ability to interact with certain external agents through a system of pores.
In particular, the matrix lets in plasminogen. When plasminogen meets the plasminogen activator inside the matrix, clot-dissolving plasmin forms.
“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,” said Yulia Chapurina, also of ITMO University.
“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.”
The researchers noted that the lifetime of drug-eluting grafts currently in use is often determined by the amount of drug stored within them. In essence, this means they can only postpone clot formation.
But the graft the researchers developed traps the drug inside a porous, protective shell, which, the team said, 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,” Dr Vinogradov said. “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.”
