YSM Issue 93.1

FOCUS
Biomedical Engineering
PHOTOGRAPH COURTESY OF YIMING ZHANG
People featured are Professor Jordan Pober (left) and postdoc researcher Tânia Baltazar (right).
Also featured between the two is the 3D bioprinter used for their research in this article.
medical problems. It was a transformative
experience,” Saltzman said.
Different Cells with Different Needs
This study, which tackles the longstanding
problems of designing and
implementing skin replacements for the
treatment of cutaneous ulcers, originated
as a collaboration between RPI and Yale,
with a focus on in vivo studies within
living organisms. The project began
by considering why nonnative skin
replacements, which do not come from
the same individual, often fail to engraft
within their hosts. This is tied to the lack
of blood vessel connections—known as
vascularization—between the skin and
the implant. In other words, our body
takes too long to perfuse the grafted
skin with blood. Without of nutrients
and oxygen, the implanted skin sloughs
off. Adding a pre-vascularized bed into
the graft accelerates the process of blood
perfusion and enhances graft survival.
“This is a project where you have
to combine four different cell types
to construct a tissue, and each has
very different needs,” Baltazar said.
Tissue engineering skin substitutes
do exist, but tend to function simply
as “expensive bandages.” That is to
say, while they protect wounds, they
do not integrate and eventually lose
their adhesive properties, because they
cannot become vascularized like real
skin. One example of this kind of skin
graft is Apligraf TM . Another alternative
to using tissue engineered constructs
includes autologous grafting, a process
by which a patch of skin is removed
from elsewhere on the subject’s body
and placed over the wound. Considering
many patients suffering from cutaneous
ulcers also suffer from diabetes, this
method may result in a second injury the
patient’s body is unable to heal.
“There were several hurdles in this
project, some of which have been
solved, others that have only been
partially solved,” Saltzman said. While
Baltazar was working on the project
as a visiting scholar at RPI, one of the
greatest challenges was the logistics of
tissue storage and transport from RPI to
Yale, where it would be implanted into
the animal models. As they worked to
develop the vascularized grafts, they often
found that the constructs would contract
following their implantation. “We had
to consider the biophysics, making
changes in how we produce the implants
to minimize this effect,” Saltzman said.
Luckily, surgical techniques improved as
the project progressed. The research team
moved from in vitro experimentation
to implanting the grafts into mice,
solving this issue with a combination of
physiology and surgical techniques.
Bioprinting Skin Grafts
Utilizing 3D bioprinting technologies,
the team successfully produced a
skin graft that was both multilayered
and vascularized, culminating in two
3D bioprinted vascularized skin grafts . . . [have] the
potential to become an ‘off-the-shelf’ clinical product.
16 Yale Scientific Magazine March 2020 www.yalescientific.org