of medicine has already begun at the University of North Texas Health
Science Center at Fort Worth. The emerging field of tissue engineering
— once the
stuff of science fiction and Star Trek episodes —
is taking shape in the center's Cardiovascular
To describe what tissue engineering is, it may be helpful
to say what it is not.
"It's a common misconception that tissue engineering is the same as bioengineering,"
says Dan Dimitrijevich, Ph.D.,
director of CRI's Laboratories of Human Cell and Tissue Engineering. "Bioengineering
involves the use of manmade materials such as plastics and metals in living
systems. The artificial heart is a bioengineered product. Tissue engineering
is the construction of living tissue. It's natural vs. manmade."
Unlike prostheses made of manmade materials, engineered
tissue becomes an integrated part of the patient.
young but growing field of tissue engineering is truly a multidisciplinary
one, with cell and molecular biologists, biomaterial and robotics engineers,
designers, imaging specialists, materials scientists and others working
together to develop materials that can replace or support diseased or
damaged tissues and restore or improve their function.
So exactly how does one engineer tissue? "You take human tissue —
skin, for example —
and you dissociate it into its cellular components," Dimitrijevich says.
These cells are used to seed a "scaffold" made of natural or synthetic
materials such as collagen or a biodegradable polymer. The scaffold is
bathed with growth factors, causing the cells to grow and adapt to produce
three-dimensional tissue. When this engineered tissue is implanted in
the body, the cells assume their intended tissue functions, and the body's
own systems help it grow and form new tissues. The scaffold is gradually
absorbed while the new tissue blends in with its environment.
"We've done it with skin and corneas," Dimitrijevich
says, "and we're trying to do it with blood vessels; several groups have
constructed cartilage." Other researchers are working to develop strategies
to repair bone, muscle, intervertebral discs and connective tissue.
People with skin damaged by burns, cancer or diabetic
ulcers are all potential beneficiaries of tissue engineering.
"We started with skin because it's readily available,"
Dimitrijevich says. Plastic surgery is a major source. "But skin is a
very complex tissue. The skin equivalent developed so far is not as close
to skin as we would like: no hair, no sweat glands. A better target is
the cornea, because it's much simpler in terms of cellular components."
disease, says Dimitrijevich, is the catalyst for the development of blood
"An artery is not just a pipe," he says. "If you replace it with a synthetic
material, it plugs up; it doesn't become a living tissue. Even the most
elaborate materials fail under the mechanical stress to which we subject
our biologically produced parts."
The use of a blood vessel taken from elsewhere in the
body to replace a diseased vessel is also problematic.
"What if the obstruction is the result of a general
vascular disease in the body?" Dimitrijevich asks. "Perhaps the piece
you're installing will eventually be just as troublesome as the piece
In addition, the vessels usually available from the patient are veins,
which are about one-third the thickness of arteries.
"They're not high-pressure systems, so they can't take
the stress forever," Dimitrijevich says. "We need something else, and
we need more of it. Our concern is to try to engineer an arterial-type
tissue for replacement in a situation like a coronary bypass."
prevention of adhesions is another area in which Dimitrijevich and Health
Science Center colleagues have made great strides. Adhesions, an almost
inevitable result of surgery, are scar tissues that form during the healing
process and glue together tissues or structures that are not supposed
to be connected.
"We're not meant to be wide open, subject to probing, gloved hands, instruments
and gauze," says Dimitrijevich. The injury to the exposed surfaces creates
a "glue" that becomes "a surgeon's nightmare if he has to go back into
the body cavity." An anti-adhesion material used in the chest cavity and
other surgery sites would be a boon to surgeons and their patients.
Dimitrijevich and his staff are studying an anti-adhesion
patch derived from engineered tissue.
"We know that the anti-adhesion patches have resolved
adhesions in four to six months," he says. "We know the protected areas
are free of adhesions, and the unprotected areas form adhesions."
If warranted, three or four such patches could be used
in a surgery, he says.
with the recent success in the field of tissue engineering, obstacles
remain. Cells must be expanded and introduced back into their three-dimensional
architecture without being genetically altered or contaminated.
"This is a very serious quality-control criterion," Dimitrijevich
says. "You don't want to implant anything that has a predisposition to
And there's the problem of rejection by the host.
"How do we make these implants invisible or tolerated
by the immune system?" Dimitrijevich asks. "Today we can give you a new
heart, but then we put you on immuno-suppressive drugs that will damage
your liver. We'll develop methods of disguising or screening the implant,
perhaps by secreting compounds that say to the immune system, 'Don't come
here ... there's nothing wrong here.' This is not impossible."
With tissue engineering, few things, it seems, are
impossible. Also under development are artificial organs such as hearts
and livers, as well as restoration of cells that produce important hormones
or enzymes. The day grows nearer when surgeons will routinely repair or
replace body parts that have failed due to disease, injury or aging.
"It really is Star Trek stuff," Dimitrijevich
says. "Wave a wand and you're healed. It's still a dream, but a dream
that is clearly in the realm of possibility."
Institutes for Discovery?
at the University of North Texas Health Science Center at Fort
Worth is one of the center's six institutes created to conduct
leading-edge research on health issues that include heart disease,
cancer, vision, physical medicine, public health and aging. Through
these institutes, Health Science Center biomedical scientists
and clinical faculty members team up with scientists and physicians
from other academic institutions, government laboratories and
the pharmaceutical, medical device and biotechnology industries.
research institutes have multidisciplinary teams involved in everything
from basic discovery and clinical research to clinical trials,
outcomes research and, ultimately, translational research and
Funding for clinical research comes from the
federal government through the National Institutes of Health and
from the private sector through pharmaceutical and biotech companies.
The sponsor of the research hires physicians to conduct the clinical
trial in a variety of health-care settings.
Industry licenses intellectual property from
the institution and develops drugs; royalties go back to the institutions
and the individuals who did the research.
Before a pharmaceutical company can begin testing
in humans, it must conduct extensive preclinical research typically
involving years of experiments. The company provides this data
to the Food and Drug Administration and requests approval to begin
testing the drug in humans.
Clinical testing in humans is usually
done in three phases, with each successive phase involving a larger
number of people. Phase one studies are primarily concerned with
assessing the drug's safety, and phase two with its effectiveness.
Phase three involves large-scale testing of the drug for a better
understanding of its effectiveness and possible adverse reactions.
A biotech center will eventually be built in
Fort Worth to house the research institutes. In addition to the
Cardiovascular Research Institute,
the list includes the Institute for Cancer Research, the North
Texas Eye Research Institute, the Physical Medicine Institute,
the Institute for Public Health Research and the Institute for
Aging and Alzheimer's Disease Research.