Scientists Develop 'In-Body Bone Factory'

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Need fresh bone for repair? Someday, you may grow your own

In the not-too-distant future, a ready source of fresh, rejection-free
bone tissue for transplant may be as close as the outside of the
patient's own shin or thigh bone, U.S. researchers report.

In experiments with rabbits, scientists were able to grow new bone
tissue from a "bioreactor" environment they created on the surface of
an animal's shin bone. After maturing for six to eight weeks, this new
skeletal tissue was harvested and used to successfully repair injured
bone elsewhere in the rabbit's body.

The advance could sidestep existing, painful procedures and
revolutionize the treatment of conditions that range from bone cancer
to chronic back pain, and fractures to reconstructive surgery, the
researchers say.

"We don't have any regulatory hurdles, and it's a very simple surgical
procedure. Our immediate goal is to use a larger animal model -- a
sheep or goat -- to get it right," said lead researcher Prasad
Shastri, an assistant professor of biomedical engineering at
Vanderbilt University in Nashville.

He believes that "within a year we should have human clinical data
ready to publish."

His team reported the findings this week in the online edition of the
Proceedings of the National Academy of Sciences.

According to Shastri, more than 300,000 Americans undergo spinal
fusion each year, usually in an attempt to end chronic back pain. In
many of these cases, doctors cut bone from the patients' hip for use
in the fusion procedure.

The muscle damage and trauma involved in this type of harvest is
"incredible," Shastri said. "And following surgery, about 30 percent
of patients complain of pain associated with the harvest site, rather
than the spinal fusion."

For many, this pain can linger for years even if their back pain
subsides.

Obviously, some better source for autologous -- the patient's own --
bone would be ideal; not only for spinal fusion patients but for those
requiring bone transplants for facial reconstruction, loss of bone as
a result of cancer, or hard-to-heal fractures.

Scientists have been able grow some types of tissue in special
bioreactors in the lab, but bone has proven too complex for this type
of engineering.

"We know, however, that there's a very powerful, wound-healing
response right there in the body" that works to grow fresh tissue,
Shastri said. But there's one roadblock: natural wound healing usually
involves fast-growing cells called fibroblasts that give rise to scar
tissue.

"But what if we could trick the body into a wound-healing response
that's in a very confined environment, where cells like fibroblasts
couldn't come in?" Shastri wondered.

That's when his team hit upon a candidate space lying between the
outer surface of long bones (such as the shin or thigh) and a thin
membrane that covers these bones, called the periosteum.

As Shastri explained, the inner side of this membrane sticks very
closely to bone and contains stem-cell-like cells with the potential
to develop into either bone or cartilage. Even better, fibroblasts are
relegated to the outer side of the periosteum -- effectively barring
them from participating in the process.

Working with the shin bone of a live rabbit, "we made a pinhole
incision and first filled the space between the bone and inner
periosteum with a salt solution, peeling it off the bone and creating
a space," Shastri said. This bubble-like space was then filled with an
FDA-approved gel rich in calcium and ideal for bone cell growth.

"So, we were basically biasing the whole environment to produce the
wound-healing effect, but in this case the only outcome that could
arise was bone or cartilage," he said.

"We were telling the bone 'Hey, you know how to do this best -- we're
just going to help you,' " he added.

Within two days, the bone-forming cells went to work, gradually moving
through various stages of bone development until, by six to eight
weeks, a mass of hard bone had formed. Even better, this mass clung to
the underside of the soft periosteum rather than the surface of the
shinbone. "That's very important, because, of course, we don't want
bone spurs to form," Shastri said.

But could this bone be used elsewhere for repair? The Vanderbilt team
harvested their first bone-factory product and transferred it to a
damaged area on the rabbit's other shinbone.

"It integrated perfectly into the injured leg," effectively repairing
the damage, Shastri said. "And we never found any adverse effect in
the site where we had created and harvested the bone -- it looks
normal, as before."

The real test will come with clinical trials in humans, he added, but
he is optimistic the new technique will work. "This could be a very
powerful tool, because it allows the patient to essentially be their
own bioreactor," he said.

Dr. Thomas Einhorn, chief of orthopedic