Angioplasty, a surgical procedure that opens blocked arteries, often involves placing a metal tube to hold arterial walls open and prevent them from collapsing once the arterial block is surgically removed. However, a bare metal stent (BMS) causes some injury to the walls of the blood vessel walls, which triggers smooth muscle cells to multiply and migrate to the site to repair the injury. This once again narrows the blood vessel—a condition called restenosis.

An article published in the journal Nature Biomedical Engineering, Exosome-eluting stents for vascular healing after ischaemic injury, reports that scientists at North Carolina State University (NCS) have developed smart stents that help reopen blood vessels and regenerate the tissue. These smart stents can heal blood vessels and repair damaged tissues because they are coated with exosomes derived from mesenchymal stem cells.

“The inflammatory response that stents cause can decrease their benefit,” says Ke Cheng, PhD, corresponding author on the article and Distinguished Professor in Regenerative Medicine at NCS and a professor in the NCS/UNC-Chapel Hill Joint Department of Biomedical Engineering. “Ideally, if we could stop smooth muscle cells from over-reacting and proliferating, and recruit endothelial cells to cover the stent, it would mitigate the inflammatory response and prevent restenosis.”

Advanced stent technology comprises drug-releasing stents (drug eluting stents, DES) that prevent all cell growth. This is counterproductive because covering stents with multiplying endothelial cells—flat cells that line blood vessels—is desirable.

“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,” Cheng says. “The stent is the perfect carrier for exosomes, and the exosomes make the stent safer and more potent in tissue repair.”

Exosomes are tiny nanoscale membranous sacs secreted by most cell types. The advantage of coating stents with exosomes are twofold. Membrane-bound exosomes camouflage the stent blocking any adverse reactions from smooth muscles or the immune system. In addition, exosomes induce endothelial cells to cover the stent and can travel to a site of injury to promote tissue repair.

Another ingenuity incorporated into the design is that the stents do not release exosomes continuously or randomly, but are induced to release exosomes in the presence of reactive oxygen species (ROS) that are a hallmark of inflammation. The researchers show that in the presence of ROS, the exosome-eluting stents (EES) release up to 60% of their secretions within 48 hours of the injury.

“Think of it as a smart release function for the exosomes,” Cheng says. “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.”

The researchers then compare their exosome-eluting stent (EES) to both a bare metal stent (BMS) and a drug-eluting stent (DES) in a rat model of ischemic injury and report that in comparison to the BMS, EES performed better in both decreasing restenosis and promoting endothelial coverage.

The authors also report that although DES perform similar to the EES in preventing restenosis, EES cause less injury to the vessel wall and attract better endothelial coverage overall. EES also promote muscle regeneration in rats with hind limb ischemia.

The researchers plan to test the stent in a large animal model as a step toward clinical trials.

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