In the U.S., adults over age 50 - endowed with a mouthful of 32 teeth - have lost an average of 12 teeth, including four wisdom molars. So reports the surgeon general, who observed that this loss of dentition can lead to problems with health, nutrition and appearance.

Synthetic tooth implants, currently in use, often provide effective replacements, but they don't wear as well as natural teeth. Implants that use titanium can lead to inflammation and bone resorption, if they become infected. What's more, as a person's bite changes with aging, such implants don't move naturally in the jaw. "Exercising" the teeth, by pressure exerted through biting, chewing and talking, helps maintain their correct position and health, as well as bones of attachment and the rest of the mouth by stimulating the growth of dental cells.

A tooth made from an individual's own cells would be a replacement for life.

Developmental molecular biologist Pamela Yelick predicts: "Within five years, we will know whether dental stem cells can be manipulated to bioengineer teeth. To generate a human tooth might take an additional five to 10 years."

Yelick, an investigator at the Forsyth Institute's department of oral biology in Boston, is senior author of a report in the Journal of Dental Research dated Oct. 1, 2002. Its title: "Tissue engineering of complex tooth structures on biodegradable polymer scaffolds."

"It's our finding," she told BioWorld Today, "that we could bioengineer mammalian teeth, that is, very specific crowns-to-be. And the fact that these tooth structures contained both dentin and enamel was significant. Previous tooth-generation efforts had managed to grow dentin but not the enamel component, so it was quite gratifying. Now our tooth structures are very small, but by studying their cell-cell interactions with the biodegradable scaffold they're seeded onto, we believe we will ultimately be able to grow teeth of different sizes and shapes."

Two Toothy Elements: Epithelium, Mesenchyme

"That's one key element," Yelick continued. "The other is that our results strongly suggest the existence of dental stem cells for the two types of cells that contribute to teeth. There are dental epithelial cells and dental mesenchymal cells. The latter are easier to propagate. Those mesenchymal dental cells form dentin, which other scientists have been able to demonstrate. The dental epithelial cells," she went on, "are a much more fragile population, which we are beginning to characterize. And that's another crucial finding toward the effort of generating biological tooth substitutes.

"To begin with," Yelick recounted, "we took immature tooth-bud cells that we obtained from the discarded jaw of a 6-month-old pig. This contained a very immature baby tooth bud that hadn't erupted, which we removed from the jawbone. You can think of that bone as a little tooth incubator, and we pulled out the sac containing the very immature tooth tissue, that had no mineralization on it. Dental stem cells were present in porcine third-molar tissue.

"Next we dissociated the cells of the tooth buds into single cells, which we first minced physically, then digested with enzymes. These gently separated the cells from one another, so that we had single-cell suspensions. We took that population of single cells and seeded them, just dripped them onto a biodegradable scaffold or matrix that we had formed in the shape of a tooth. But the teeth we actually did form were much smaller than the scaffold itself.

"The scaffold is composed of polyglycolic acid," Yelick continued. "It's used in absorbable surgical sutures, and also in tissue engineering in that it's biodegradable, and dissolves in aqueous solutions. It's very important," she explained, "that the cells have some sort of matrix to sit onto so that they can migrate along some support and organize themselves in order to start to differentiate and grow into teeth.

"Once the cells were seeded onto the scaffold, the matrix," Yelick went on, "we needed to grow the teeth in an environment that has an adequate blood supply to support the growth of higher-order tissue structure. If tissues grow too large and don't have a blood supply that delivers nutrients and oxygen, they just die - they necrose. A method devised by the lab of Joseph Vacanti, a Forsyth co-author of our paper, was to surgically implant the scaffold into a fatty vascularized tissue called omentum, which is in the abdomen of the rat, near its small intestine. Within 30 weeks, small [2x2x2 millimeters], recognizable tooth crowns had formed, containing dentin and enamel. That's just where we grew these two structures - epithelium and mesenchyme - like an incubator. Obviously, we would prefer to grow teeth in the jaw, and we're working on those experiments. For now, we adopted this pretty successful strategy, which is working very well.

"In our currently ongoing research," Yelick said, "we need to answer two obvious questions. One of them is: What are the cells that form the teeth? For an answer, we need to identify and characterize those dental stem cells. Another area we must investigate is how we can manipulate the size and shape of the teeth that we grow. How can we modify the interactions of the cells with each other and with the scaffold to grow larger teeth structures?"

Living Teeth Outdo Store-Bought Dentition

"Based on the enthusiasm we received by this journal article," Yelick observed, "and just in daily conversations with people, I think that there's quite a demand for tissue-engineered teeth. The advantage of a living tooth is that it preserves the health of the surrounding tissues much better than an artificial prosthesis. Teeth are living, and they respond to your bite. They move, and in doing so they maintain the health of the surrounding gums, of the bone underlying the teeth, and of the opposing teeth on the other side. So a living tooth would maintain the vitality of all those tissues; artificial prostheses don't do that.

"The institute," she allowed, "has filed patent applications covering the work in progress and in prospect. We don't have a commercial partner yet, but we are interested in identifying potential collaborators. First, we need more funding to support this research. And then ultimately, being research scientists, we wouldn't be implanting these structures ourselves, so I assume that we definitely need a clinical partner. I would say," Yelick concluded, "that the market potential is very large."