Tissue engineering holds promise for mouth wounds

Scientists have a pretty good handle on how to teach human cells to do tricks in the laboratory, such as getting soft cells from the mouth's lining to form bone.

But in the real world, accomplishing such feats is more complex. Regenerating the jaw bone of a person undergoing radiation therapy for cancer means managing the constant bacteria bath of a human mouth as well as compensating for the damage of radiation.

"It's not just a question of whether we can make new tissue in a perfect condition. Now we're mimicking what can really happen in a person, and we don't know if the rules of regeneration might be totally different," says Paul Krebsbach, associate professor at the School of Dentistry.

Krebsbach participated in a panel discussion last week entitled "Tissue Engineering for the Head and Neck" at the American Association for the Advancement of Science annual meeting in Washington, D.C. He also took part in a congressional briefing about stem cells in dental research.

Tissue engineering typically involves harvesting a small sample of cells, treating them in the lab, then reintroducing the cells into a damaged area, like a jaw bone damaged so severely it cannot heal on its own. A tiny scaffold helps direct the engineered cells to the right place. The scaffold then dissolves once the cells begin to generate to fill in the wound.

Krebsbach and his collaborators aim to teach human cells how to fill in wounds on the head and neck. (Image courtesy Paul Krebsbach)

"In certain kinds of defects, the body cannot heal itself and the body needs a jumpstart," Krebsbach says. Healing a large wound, such as one created when a cancerous tumor is removed from the jaw, often means taking a bone graft from someplace such as the hip. That approach has problems both for the wound at the donor site and for the site where it is implanted, Krebsbach says.

In addition to the sometimes-messy real world applications of tissue engineering, Krebsbach discussed the potential for combining unrelated therapies to improve the benefits of tissue engineering.

For example, parathyroid hormone—given to patients with osteoporosis—stimulates bone growth in patients. Krebsbach says there is a potential to use the hormone for similar gains in tissue engineering new bone.

Bone morphogenetic proteins (BMP) help cells differentiate into specific kinds of bone, and encouraging cells to make more BMPs during tissue engineering also can ramp up the effects.

"Together these therapies can overcome compromised environments," he says.

These approaches are not yet being tested in humans, but Krebsbach says some small clinical trials are under consideration.

If the combination therapy approach works, Krebsbach says the next step would be working with engineers to develop anatomically correct scaffolding with the same curvature and contours of natural bones. That would help a patient develop new bone almost indistinguishable from nature's original equipment.

Many U-M researchers have focused their tissue engineering efforts on the head and neck, in part because U-M Dentistry plays a leading role in the effort. Dentists have a long tradition of finding ways to fill tooth cavities that will not heal on their own, Krebsbach says.

At U-M, collaboration includes dentists, medical doctors and engineers, among others. They all bring a different perspective, and it leads to scientific advances that couldn't happen in any one discipline, Krebsbach says.

"That's the beauty of tissue engineering. It has to be multi-disciplinary to work," Krebsbach says.