Scientists have developed a new type of smart stent that can help prevent some of the complications these implants bring. The stent is coated in a substance that minimizes the inflammatory response, while promoting tissue repair.
Angioplasty is a common procedure to pry open blocked arteries. A tiny balloon is inserted into the blood vessel and inflated at the site of the blockage, then a stent is usually placed to keep the vessel from narrowing again after the balloon and blockage have been removed.
But unfortunately it doesn’t always work like it should. If the stent injures the blood vessels, it can cause the smooth muscle cells of the arteries to proliferate and try to patch up the damage. This inflammatory response can narrow the artery again, a condition called restenosis.
More advanced stents were later created to counter this problem. Drug-eluting stents (DES) are coated in drugs that reduce cell proliferation, but frustratingly they also prevent the growth of endothelial cells, which are crucial for proper integration of the implant. Finding a balance between the two types of cells was the goal of the new study.
“Ideally, if we could stop smooth muscle cells from over-reacting and proliferating, but recruit endothelial cells to cover the stent, it would mitigate the inflammatory response and prevent restenosis,” says Ke Cheng, corresponding author of the study.
To do so, the team made a new kind of coating that contains exosomes, tiny sacs that are excreted by all cell types to help them send “messages.” The exosomes help in three different ways – firstly, because they’re similar to cell membranes, the immune system doesn’t recognize them as foreign, preventing an inflammatory response. They also encourage endothelial cells to proliferate on the stent surface. And as an added bonus, they can even pitch in and promote tissue repair in case of injury.
But the particularly clever bit is the trigger that releases the exosomes in the first place. Rather than just let them all go at once and potentially waste the therapy, the smart stent only releases exosomes in response to molecules called reactive oxygen species (ROS), which are produced in higher numbers during an inflammatory response.
“Think of it as a smart release function for the exosomes,” says Cheng. “Ischemic reperfusion injuries, which occur when blood flow is diminished and then reestablished, create a lot of ROS. Let’s say the heart is damaged by ischemia. The enhanced ROS will trigger the release of the exosomes on the stent, and regenerative therapy will travel through the blood vessel to the site of the injury.”
In tests in the lab, the team found that the smart stents successfully released up to 60 percent of their exosomes within 48 hours of an injury, triggered by higher numbers of ROS. Next, the team tested them in rats with ischemic injuries, comparing them to other drug-eluding stents and bare metal stents. They found that their new device was better at preventing restenosis and promoting endothelial cell growth, and reduced damage to blood vessels.
“This bioactive stent promotes vascular healing and ischemic repair, and a patient wouldn’t need additional procedures for regenerative therapy after the stent is in place,” says Cheng. “The stent is the perfect carrier for exosomes, and the exosomes make the stent safer and more potent in tissue repair.”
It’s a promising step, but of course it’s still very early days for this new system. The team next plans to test it out in larger animals. In the meantime, other smart stents are also in development, which could help prevent restenosis by sending wireless alerts at the first signs of narrowing arteries.
The research was published in the journal Nature Biomedical Engineering.
Source: North Carolina State University