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Scientists Develop 'In-Body Bone Factory'

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

THURSDAY, July 28, 2005 (HealthDay News) -- 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 surgery at Boston University Medical Center, had a more cautious response to the findings. Einhorn said he's noted bone formation within the periosteum in his own clinical practice, "so it's no surprise that this is possible to do."

"It's a very simple concept. In fact, it's so straightforward that I would be surprised if it doesn't work in patients," he said.

But he's also not persuaded that growing additional bone is much of an improvement over harvesting bone that's already there (i.e., in the hip), since both methods still require surgical interventions. "I'm not convinced that in a clinical setting its going to be a great advance," he said.

Shastri believes the technology may have implications that extend far beyond bone grafts, however. "A lot of organs have a covering membrane -- the liver has a little membrane, the pancreas does, as does the heart," he said.

Tissues from all of these organs are in high demand for transplant, but have so far proven impossible to reproduce with real quality in the lab.

In-body tissue factories may someday allow patients a means of growing their own tissues for transplant, without the ethical or rejection issues that come from donated tissue, Shastri said.

"It's a very powerful paradigm," he said. "We're headed in the right direction, and it's just a matter of working relentlessly toward it."

More information

For more on spinal fusion, visit the North American Spine Society.

SOURCES: Prasad Shastri, Ph.D., assistant professor, biomedical engineering, Vanderbilt University, Nashville, Tenn.; Thomas Einhorn, M.D., chairman, department of orthopedic surgery, Boston University Medical Center, Boston; July 25-29, 2005, Proceedings of the National Academy of Sciences
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