With the University of Pittsburgh’s development of a
cell-free, biodegradable artery graft comes a potentially transformative change
in coronary artery bypass surgeries: Within 90 days after surgery, the patient
will have a regenerated artery with no trace of synthetic graft materials left
in the body.
Research published online June 24 in Nature Medicine
highlights work led by principal investigator Yadong Wang, a professor in
Pitt’s Swanson School of Engineering and the School of Medicine’s Department of
Surgery, who designed grafts that fully harness the body’s regenerative
capacity. This new approach is a philosophical shift from the predominant
cell-centered approaches in tissue engineering of blood vessels.
“The host site, the artery in this case, is an excellent
source of cells and provides a very efficient growth environment,” said Wang.
“This is what inspired us to skip the cell culture altogether and create these
cell-free synthetic grafts.”
Wang and fellow researchers Wei Wu, a former Pitt postdoctoral
associate (now a postdoctoral associate at Yale University), and Robert Allen,
a Pitt PhD student in bioengineering, designed the graft with three properties
in mind. First, they chose a graft material—an elastic polymer called PGS—that
is resorbed quickly by the body. Then they examined graft porosity and selected
parameters that allow immediate cell infiltration. Wang’s team borrowed a
procedure developed by another team of Pitt researchers—David Vorp, professor
of bioengineering and surgery, and William R. Wagner, interim director of the
University’s McGowan Institute for Regenerative Medicine and a professor of
surgery, bioengineering, and chemical engineering—wrapping the vascular graft
with a fibrous sheath to trap the cells. Finally, Wang and his fellow
researchers wanted a coating for the grafts that would reduces blood clotting
and bind many growth factors, so they used heparin, a molecule that does just
that.
“The results were porous grafts that are suturable,” said
Wang. “And the rapid remodeling of the grafts led to strong and compliant new
arteries. The extent of the changes in the grafts that occurred in just 90 days
was remarkable.”
Wang and his colleagues made grafts as small as 1 mm in
diameter and monitored the graft’s transformation in vivo for three months.
Because the graft was highly porous, cells were easily able to penetrate the
graft wall, and mononuclear cells occupied many of the pores within three days.
Within 14 days, smooth muscle cells—an important blood vessel builder—appeared.
At 28 days, cells were distributed more evenly throughout the graft. At 90
days, most inflammatory cells were gone, which correlated with the
disappearance of the graft materials. The artery was regenerated in situ and
pulsed in sync with the host. Furthermore, the composition and properties of
the new arteries are nearly the same as native arteries.
“This report is the first that shows a nearly complete
transformation of a synthetic plastic tube to a new host artery with excellent
integration within three months,” said Wang. “Most likely, the amount of time
it takes to regenerate an artery can be further shortened as we refine the
system.”
Current approaches toward tissue-engineered arteries require
a long production cycle because of the required cell culture steps. The newly
developed graft is made in a few days, stores in a dry pouch at ambient
temperature, and is readily available off the shelf. The ease of use and
storage are similar to the conventional Dacron® grafts.
The project was funded by the National Heart, Lung, and
Blood Institute, part of the National Institutes of Health.
