PITTSBURGH (Sept. 24, 2020) … Just as a climbing plant needs the
right trellis to thrive, a small-diameter tissue-engineered vascular graft
(TEVG) needs the right scaffold to transform seeded cells into a native-like
artery that can save a life.
A team led by the University of Pittsburgh’s David A. Vorp
received a $1.1M award from the National Institutes of Health to optimize this
emerging technology for cardiovascular disease. They will examine the best
combination(s) of active “payload” and scaffold to develop a feasible alternative
to the decades-old practice of using vessels harvested from a patient’s own chest
Coronary heart disease – a worldwide leading cause of death –
damages arteries that carry a vital supply of blood, oxygen, and nutrients to the
heart. Surgeons typically replace damaged vessels with healthy autologous ones
that are harvested from a different part of the patient’s body, but according
to Vorp, they are not an ideal substitution.
“Autologous vessels are not ideal in that they are limited
in number and/or are not naturally designed to function as an artery,” he said.
“They have been the gold standard in bypass grafts, but in recent years,
companies have begun clinical testing on TEVGs developed in research labs like
Vorp’s team has developed a TEVG based on the well-known regenerative
power of mesenchymal stem cells (MSCs), which both prevent blood from clotting
on the implanted TEVG and recruit host immune cells that participate in the regeneration
process. MSCs are adult stem cells most often derived from a patient’s bone
A successful TEVG will grow and remodel into a native-like
artery. It consists of a scaffold that provides a framework for seeded cells,
which when given environmental cues, will promote tissue regeneration. In this
project, Vorp and his collaborators will examine a variety of successful
“payloads” and scaffolds to determine which combinations work best.
For the payload, the group will study a cell-based and
cell-free approach using both MSCs and – for the cell-free approach – certain immunoregulatory
factors that the MSCs secrete.
“We believe that the regulatory pathway for a cell-free
configuration would be faster if it is shown to be as effective as a cell-based
approach,” Vorp said.
They will assess each feasible combination of payload and
biodegradable scaffold, which will be made from materials in the polyurethane
and silk families.
“Our previous work has focused on the ability of some of our
payload and scaffold combinations to remodel into a successful TEVG when
implanted as an aortic replacement graft in rats,” said Vorp, the John A.
Swanson Professor of Bioengineering at Pitt’s Swanson School of Engineering and
member of the McGowan Institute for Regenerative Medicine. “This NIH Catalyze
grant will now allow us to more rigorously optimize the grafts in the small
animal model to narrow down the number of combinations to be tested in a large
Finding the best combination(s) of payload and scaffold is
only the first step of this project. It is part of a two-phase Catalyze grant
from the NIH’s National Heart Lung and Blood Institute, which includes a
one-year R61 grant in which the team must achieve the necessary milestones to
be eligible to transition to the two-year R33 award.
In the second part of the project, the group will use the
R33 award to address the manufacturability and other clinical translational
aspects of a TEVG, including large animal testing of the best configuration(s).
“We will work with ‘accelerator partners,’ including
RoosterBio, Inc. and Pitt’s Clinical & Translational Sciences Institute, as
well as regulatory consultants to begin addressing manufacturability for
clinical translation,” Vorp said.
Though there are many advantages to TEVGs, the technology
also has its challenges. The researchers hope that finding an optimal
configuration will decrease the chance of stenosis, a common complication where
the vessel narrows and limits blood flow.
The goal of this award is to find a design that can advance to
the clinical phase of development and eventually reach the market as a better-quality
graft for bypass surgery.
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Contact: Leah Russell