Medical Design Briefs - June 2021 - 31

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Exosomes (magenta) released from a stent in the blood vessel. (Credit: Cheng Lab)
Medicine at NC State and a professor in
the NC State/UNC-Chapel Hill Joint
Depart ment of Biomedical Engineering.
There are drug-eluting stents currently
in use coated with drugs that discourage
cell proliferation, but these
anti-proliferative drugs also delay stent
coverage by endothelial cells - which
are the cells healthcare providers want
to coat the stent.
To solve this problem, Cheng and his
team developed a stent coating composed
of exosomes derived from mesenchymal
stem cells. Exosomes are tiny
nano-sized sacs secreted by most cell
types. The idea behind the coating was
two-fold: first, since the exosomes are
composed of materials not much different
from cell membranes, they camouflage
the stent to trick smooth muscle
cells and the body's immune system.
Second, the exosomes promote coverage
of the stent by endothelial cells and,
in the case of injury, travel downstream
to the site to promote tissue repair.
To prevent premature depletion of
the therapy, the stent releases exosomes
when it encounters reactive oxygen
species (ROS) - which are more prevalent
during an inflammatory response.
" 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. "
Medical Design Briefs, June 2021
Cov
The research team performed in vitro
testing to ensure biocompatibility and
test the release mechanism. They found
that in the presence of ROS, the exosomes
released up to 60 percent of their
secretions within 48 hours post-injury.
In a rat model of ischemic injury, the
researchers compared their exosomeeluting
stent (EES) to both a bare metal
stent (BMS) and a drug-eluting stent
(DES). They found that in comparison to
the BMS, their stent performed better in
both decreasing stenosis and promoting
endothelial coverage. While the DES performed
similarly to the EES in preventing
restenosis, the EES was less injurious to
the vessel wall and had better endothelial
coverage overall. In addition, the exosomes
released from EES promoted muscle
regeneration in rats with hind limb
ischemia. The researchers plan to test the
stent in a large animal model with an eye
toward eventual clinical trials.
" 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. "
The research appears in Nature
Biomedical Engineering and was supported
by the National Institutes of Health and
the American Heart Association. NC State
postdoctoral research scholars Shiqi Hu
and Zhenhua Li are co-first authors.
This article was written by Tracey Peake,
NC State. For more information, visit https://
news.ncsu.edu.
www.medicaldesignbriefs.com
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Medical Design Briefs - June 2021

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