In patients with congenital defects or accidental injuries, the jawbone can hardly be replaced. The bone is curved and complex, ending with a joint covered with a layer of cartilage. Both parts have to withstand enormous loads when chewing.
"It's one of the most stressed bones in the human body," said Gordana Vunjak-Novakovic, professor of biomedical engineering, medicine and dentistry at Columbia University in New York.
In an article published in Science Translational Medicine on Wednesday, she and her colleagues reported a surprising success: they succeeded in growing replacement bones along with their joints from the stem cells of pigs. A clinical trial in patients with severe birth defects will begin shortly.
The researchers hope that one day the same technique can be used to grow other replacement bones and joints, including the knees. Even if the strategy works, it will be years before those in need of new jawbones or joints can construct them from their own cells.
Dr. Sidney Eisig, chair of hospital dentistry at Columbia University, said the work began in part because of frustration at the opportunities for surgeons like him.
When a patient needs a replacement jawbone, grafts from other parts of the body can be impractical. They may not be the right shape – most bones are straight and relatively flat, while the jawbones are curved.
"It's hard to take a straight piece of bone and curve a curve on it," said Dr. Icy. In addition, the amount may be insufficient and the ingestion of grafts requires a second surgical site on the patient.
Metal prostheses can replace the joint that the jawbone is attached to – the TMJ or TMJ. Prostheses are used on patients with arthritis so severe that the joint is destroyed, making it difficult and very painful to open your mouth even a little.
However, these artificial joints haven't been studied long-term to see how well they can hold up, said Dr. Tara Aghaloo, a maxillofacial surgeon at the University of California at Los Angeles who was not involved in the study.
It is difficult for surgeons to know whether these prostheses should be used on younger patients with severe arthritis, and a significant proportion of patients are allergic to the metal in the joints.
"I always thought there had to be a better way to do this," said Dr. Icy.
About 10 years ago he noticed a scientific paper by Dr. Vunjak-Novakovic, in which she reported constructing a human temporomandibular joint condyle – a relatively small piece of bone in the shape of an ankle – from stem cells that she had taken from human fat.
"I ran to her lab and said," Gordana, do I have a box for you? "Said Dr. Eisig.
He challenged Dr. Vunjak-Novakovic asked to use the joint to create a curved bone in a larger animal. They decided that a pig would be ideal – the animals have jaw joints similar to humans.
She and her colleagues needed a way to sculpt the jawbone and decided to use cowbones as a kind of scaffolding. The bones from which cow cells had been removed were shaped by computer-controlled milling so that each bone could be precisely made for a single animal.
The stem cells required for bone formation were obtained from the pork fat and removed by liposuction. The researchers identified a group of stem cells that were supposed to turn into bones and placed them in the scaffolding.
The team instructed another group of stem cells to grow into cartilage and placed these cells on the scaffold. Five weeks later the new bone cartilage grafts were ready.
The team sent the bones to Louisiana State University, where staff introduced them into pigs whose jawbones had been removed. "As soon as they woke up, they started moving and eating," said Dr. Vunjak-Novakovic.
The observation that the animals were able to eat immediately was an encouraging sign.
Six months later, the researchers sacrificed the animals and examined the new bones. The cow bones had been reabsorbed into the pigs' bodies. What was left was a jawbone indistinguishable from the one that had originally been there.
Six patients who have shortened faces with an open bite will take part in the clinical trial. Surgeons twist their jaws and insert an artificial bone to fill the gap, making their faces longer so they can close their mouths.
Dr. Eisig had waited decades for such progress, he said. "It's preliminary, but it's very exciting," he said. "I'm glad it happened while I'm still practicing."