WPI team has developed biopolymer microthreads for tissue regeneration, wound healing, and cell therapy applications. |
Development
of new therapies for a range of medical conditions—from common sports
injuries to heart attacks—will be supported by a new production-scale
microthread extruder designed and built by a team of graduate students
and biomedical engineering faculty at Worcester Polytechnic Institute
(WPI).
The
new microthread extrusion system is in the final stages of testing and
validation, and will soon be manufacturing thousands of hair-like
biopolymer threads a day at WPI’s Life Sciences and Bioengineering
Center at Gateway Park.
The computer-controlled system is capable of continuous extrusion of microthreads with a range of diameters and quantities.
“The
use of these microthreads is spreading across labs here at WPI, and to
our collaborators around the country,” said Glenn Gaudette, associate
professor of biomedical engineering at WPI, who oversaw the development
of the new extrusion system. “So we needed greater quantities of the
microthreads and a system to standardize and control the production
process.”
The
idea for using microthreads as a basis for tissue engineering was
developed in the laboratory of George Pins, associate professor of
biomedical engineering at WPI, who was looking for a better way to
repair the anterior cruciate ligament (ACL) in the knee. The current
surgical treatment for ACL tears or ruptures, which affect an estimated
100,000 people in the United States each year, involves removing a
section of healthy tendon from another part of the body and grafting it
into the knee to replace the ACL. While surgery is often required to
help patients regain full use of the knee, the current approach is not
considered ideal because it injures one part of the body to repair
another.
“The
ACL, like other ligaments and tendons, is a fibrous cable-like
structure,” Pins said. “So the original idea was to use thin collagen
threads, bundled into cables that mimic the natural structures in the
body, as a scaffold for the tissue engineering that would be used to
replace the ACL.”
Collagen
is the main structural protein of the body. It’s the building block for
skin and connective tissues such as tendons, ligaments, muscle, and
cartilage. So Pins and his lab team theorized that thin threads of
collagen would be well-tolerated by the body. As the work continued, the
team also began making microthreads from fibrin, which is the main
protein in blood clots; since clotting is an early response to injury
Pins believed that fibrin threads could become useful scaffolds for
wound-healing applications.
Initially,
Pins and his lab team made each thread by hand, using a large syringe
to push out a bead of collagen or fibrin, draw it into a bath of
solution, then lift it out by hand to dry suspended over the edges of a
cardboard box. “I always looked for the student with the steadiest hands
to draw out the threads,” Pins said, noting that it was difficult to
get the threads to be consistent in diameter and length.
While
the hand-drawn method demonstrated the promise of the concept, Pins
challenged several of his undergraduate students to develop an automated
system for making the threads in a consistent manner. Two Major
Qualifying Project (MQP) teams tackled the challenge over the course of
two years. Working collaboratively with WPI faculty members in
mechanical engineering and robotics engineering, they developed a
working bench-scale prototype that automated most of the thread
production process. “The prototype worked well, and produced more
consistent threads,” Pins noted.
By
early 2010, interest in the microthreads had expanded beyond Pins’s
lab, as colleagues at WPI saw opportunities to use them in their own
areas of research. With demand for new threads growing, Paul Vasiliadis,
a member of one of the MQP teams, began planning to take microthread
production to the next level. After earning his bachelor’s degree in
2010, Vasiliadis joined Gaudette’s lab as a graduate student and became
the lead developer of the production-scale extrusion system now being
commissioned. Computer-controlled, the new system is capable of
continuous extrusion with a range of specified thread diameters and
quantities.
“I
think this project shows the importance of bringing together
multidisciplinary teams, focused on the biology and the engineering, to
create solutions that will meet real clinical needs,” Gaudette said.
The
Pins lab continues to develop the microthread technology for use as
potential ligament and tendon scaffolds while also working to optimize
the composition and mechanical properties of the threads. For example,
they are experimenting with ways to control the tensile strength of the
threads, and to control the rate at which the threads dissolve once
implanted in the body. They have also developed new technologies to
tailor the surface topographies and biochemistries of the microthreads
to provide specific signaling cues that they predict will direct
cell-mediated tissue responses.
In
Gaudette’s lab, the threads are being used as biological sutures to
deliver bone marrow–derived adult stem cells known as human mesenchymal
stem cells (hMSCs) to cardiac tissue damaged by disease or trauma.
Studies by Gaudette and others have shown that when hMSCs are delivered
to damaged hearts, they moderately improve cardiac function. A major
challenge in these studies, however, is getting sufficient numbers of
hMSCs to engraft into the damaged heart tissue. Prior methods of
injecting the cells into the bloodstream, or directly into the heart
muscle, yielded low results, with 15 percent or fewer of the cells
injected actually surviving and attaching to the heart muscle. Using the
microthreads to deliver cells to the heart has changed that dynamic.
“The
early studies are very promising,” Gaudette said. “We have developed
ways to seed and grow the stem cells on the microthreads, and deliver
them directly to the area needed, with more than 60 percent of those
cells successfully engrafting. That’s a major improvement.”
Other
researchers at WPI are using fibrin-based microthreads as a platform to
restore muscle tissue that was damaged by traumatic injury. In those
studies, the microthreads do double duty: they are seeded with new cells
that could regenerate muscle tissue, and they serve as a muscle-like
scaffold to promote the body’s own healing and regenerative processes.
“This
is becoming a platform technology, growing in ways we hadn’t imagined
when we first began this line of research,” Pins said. “It’s exciting to
see the clinical potential for this technology accelerating. And, as an
educator, it’s gratifying to know how fundamentally important the
students’ contributions have been to this work.”
With
testing, validation, and operator training now under way, the new
extrusion system is expected to be supplying WPI labs with
research-grade microthreads later this spring.
Source: Worcester Polytechnic Institute