Body Builders
Tissue engineers like
Kristi Anseth and
Kyriacos Athanasiou can
rebuild you. They have the technology. Well, almost.
For Kristi Anseth, a chemical engineer by training, the path
to a new way of thinking about repairing knees and broken bones
meandered through the dentist's office.
As a researcher at the
Massachusetts Institute of Technology a
decade ago, she was working with the materials dentists use to
fill teeth - alongside an interdisciplinary group of biochemists,
clinicians, and others - when an idea struck her. If dentists could
fill a cavity with a chemical composite and shine a light on it to
cause it to harden, why couldn't she engineer something similar
for orthopedists dealing with fractures?
"Wouldn't it be neat," she says, "to design something similar to
what you do to someone's tooth and use it in a bone defect to get
the bone to heal faster? Or in some instances where the bone won't
heal at all?"
When she started talking to orthopedic surgeons about her idea,
they pointed her in a second direction: cartilage damage in knees.
Cartilage doesn't heal itself, and the surgeons were doing more and
more total knee replacements (more than 200,000 are performed
annually). The body has plenty of cartilage. What if some of the
cells from that tissue could be isolated and placed into the knee,
and then the cells were encouraged to grow? What if she could use
the model of those dental materials and create a sort of
scaffolding for cartilage cells?
That set her on a decadelong search for innovative ways to heal
bones and knees as well as to grow other tissues. To do that,
Anseth, a medical investigator for the Howard Hughes Medical
Institute and a professor at the University of
Colorado, designed
polymers that emulate living tissue and form the scaffolding to
rebuild damaged knees and broken bones. For bones, Anseth and her
team developed special polymers to be placed inside a severe
fracture, where they encourage the bone to heal by releasing
medications and hormones. Because the process is light-sensitive,
it can be turned on and off through the use of ultraviolet light.
It's one of several processes that Anseth has developed that have
been licensed for use by
biotechnology companies.
The pioneering research by Anseth and others in tissue engineering,
a relatively new field, offers the hope of starting new models for
healing. "I am convinced that in our lifetime we're going to see
more clinical therapies that use tissue engineering strategies to
at least improve quality of life, if not completely heal us," she
says.
ANSETH'S BARRIER-BUSTING research career parallels the rise
of tissue engineering, a term that didn't exist a little over a
decade ago. The area combines a dizzying number of specialties,
including bioengineering, chemical engineering, molecular and
cellular biology, biochemistry, and physics.
It requires researchers like Anseth and Rice University's Kyriacos
Athanasiou to not only reach across disciplines but to think about
problems in new ways within their own areas of expertise.
Athanasiou, whose work has yielded 28 patents and 12 products
approved by the Food and Drug Administration, began researching
cartilage in 1989. "All of my work in what I would call the early
stages of tissue engineering cemented in my mind the view that we
can harness the ability of cells to make tissues in vitro," he
says, "and then one could go about regenerating tissues that
normally could not be regenerated on their own."
Athanasiou, the past president of the Biomedical Engineering
Society, is working on engineering cartilage that does not require
scaffolding for use in the knee and the jaw. "We have discovered
that when it comes to cartilage tissue engineering, we can make
tissue that looks like real tissue and has all the characteristics
of real tissue without using scaffolding," he says.
Using cartilage cells from donors, he has grown scaffoldless
cartilage of various shapes and contours in vitro, which means that
osteoarthritis could eventually be treated by resurfacing the
entire joint with newly grown cartilage.
That doesn't mean there aren't obstacles. The issue of rejection -
because the cells are not compatible with the patient - is looming
on the horizon, but the risk may not be as severe with cartilage as
it is with other tissues. "We can tissue-engineer the structures,"
Athanasiou says. "The problem that we are faced with - between what
we're making now and turning this into a patient-specific product -
is the sources of cells we have to use."
They have been using bone marrow cells and human embryonic stem
cells, which are limited and controversial. One of the recent
research interests is to begin using skin cells. "Clearly,"
Athanasiou says, "that would be a boon."
ANSETH AND ATHANASIOU are reluctant to predict when their
technologies will become commonplace. "If we stay with cartilage, I
believe we are within five years of seeing the applicability of
that work," Athanasiou says.
Cartilage, bone, and skin (which Anseth's group has created) are
just the beginning. Anseth is also working on engineering tissue
heart valves that have the ability to grow, which would replace
current methods and offer a striking possibility for children born
with heart-valve defects. That is the ultimate, of course -
regenerating organs such as hearts, livers, and kidneys. There are
more than 40,000 people in need of heart transplants in the United
States annually, but only 2,000 to 3,000 donor hearts are available
each year for such transplants.
“It gets really complex,” Anseth says, “when you start to think about how to regrow something like a liver, which has a complex metabolic function, a blood supply. You’d have to engineer blood vessels, engineer nerves, plus know how to culture the important cells in the liver.
“I think we’re a long way away from regenerating an organ,” she continues. “But I think that’s the holy grail of the field, and we’re working diligently.”