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Beyond the gum line

By Alex Piazza
apiazza@umich.edu

The average American spends about 38 days of their life brushing their teeth.

The goal is a nice set of pearly whites and a clean bill of health from the dentist.

But dentistry at the University of Michigan goes far beyond cavities and cleanings.

U-M dental researchers work to rebuild human lips for wounded combat veterans. They research food preservatives and their ability to slow cancer. And they study the relationship between heart attacks and oral health.

“When you think about dentistry, the first thing that comes to mind for many people is their routine checkups, cleanings and occasionally a filling,” said U-M School of Dentistry Dean Laurie McCauley. “What many people don’t realize is that sophisticated biomedical research is conducted every day at the School of Dentistry. Our talented researchers are performing groundbreaking studies that will change your perception of dentistry and may one day even change your life.”

Below are three examples that show the diversity and broad impact of interdisciplinary research at the U-M School of Dentistry.

Cardiac connection

A man jogs along an outdoor trail when a sudden sharp pain engulfs his chest.

His breathing changes and he breaks out into a cold sweat.

Within seconds, he grows nauseous and is forced to sit down on a nearby bench.

He is among the 720,000 Americans who experience a heart attack each year, according to the U.S. Centers for Disease Control and Prevention.

He is rushed to the hospital, where he survives his first bout with cardiovascular disease.

But what if his brushing habits somehow factored into his recovery from a triple bypass?

That’s the focus of an ongoing research project led by Hector Rios.

“Dentistry research doesn’t just focus on the oral cavity,” said Rios, U-M assistant professor of dentistry. “Oftentimes, we look beyond the mouth to examine how oral health impacts your overall well-being.”

Take periostin for example. Rios’ latest research focuses on the multifaceted protein and its ability to increase tissue strength.

Teeth are exposed to a number of environmental stressors, from oral bacteria to repetitive chewing. These stressors can lead to deterioration of the bones and soft tissue lining the mouth.

“Dentistry research doesn’t just focus on the oral cavity,” Rios said. “Oftentimes, we look beyond the mouth to examine how oral health impacts your overall well-being.”

Deterioration can cause periodontal (gum) disease, which can spur infection that spreads beyond the oral cavity.

“Once the seal around your tooth is broken, it becomes a systemic burden,” Rios said. “Sustained exposure to these pathogens can significantly decrease the presence of periostin in your body, which could have a detrimental impact on other organs.”

Research shows that after people suffer a heart attack, many of them produce an increased level of periostin in their blood. The periostin is believed to aid in repair and recovery.

“We want to understand if there are prognostic implications when you have healthy gums, or infected gums, and a heart attack occurs,” he said. “In order for the body to cope with a heart attack, you would expect a lot of increased levels of periostin. If you induce a heart attack in a non-human model that is completely depleted of periostin, the mortality and morbidity after that injury is highly increased. They cannot repair properly because of the absence of periostin.”

Rios plans to work with U-M researchers across campus to embark on clinical trials to validate his research model.

“If people are able to practice better oral health, they can reduce the possibility of infection, and they could be better equipped systemically to deal with a heart attack,” he said.

Lip service

A combat veteran returns home from Afghanistan months after a roadside bomb mangles her face.

She struggles to speak with her family and dinner is difficult to eat, as shrapnel from the explosion destroyed portions of her lip.

She could undergo reconstructive surgery, but lips are tricky to rebuild. Common solutions involve tissue grafts from the arm, but a lack of muscle in that region often leaves patients upset with the final esthetic and functional result.

“These men and women go overseas and put their lives on the line, only for some of them to return home with these debilitating injuries,” said Stephen Feinberg. “I want to help them so they can return to society with an enhanced quality of life.”

Feinberg, a U-M professor of dentistry and surgery, works closely with the U.S. Department of Defense to help war veterans who have suffered injuries on the battlefield.

“Facial injuries are much more common in today’s war environment than they were 30 years ago,” he said. “They have body armor to protect their torso, but it’s difficult to protect the face without inhibiting their ability to function in combat.”

Feinberg is working with researchers across campus to develop a platform technology in which surgeons create designer complex tissue grafts from an individual’s own tissue that can grow and mature on their back muscle.

First, researchers create and fabricate specialized tissue in the lab that they insert in a concentrated way on the patient’s back muscle. This will eventually serve as a composite soft tissue graft composed of cells, skin and muscle with an opening created through the designer graft to create the lips of the mouth.

“This is a novel approach because nobody has tried anything like this before,” Feinberg said.

After a few weeks, surgeons remove the composite soft tissue graft with its arteries, veins and motor nerves for reapplication and attachment on the patient’s face.

“This is a novel approach because nobody has tried anything like this before,” Feinberg said.

Clinical trials are expected to commence this year to assess the success of the procedure, though Feinberg remains confident in his unique approach to rebuilding human lips through tissue engineering.

And he doesn’t plan to stop with lips. Combat veterans return home with a number of injuries, many of which are caused by roadside bombs.

That’s why Feinberg plans to research ways to reconstruct eyelids, noses, vaginas and anal sphincters.

“We’re also looking at severe burn injuries,” he said. “Where is the one place on your body that is unharmed in the event of a severe burn? Oftentimes, it’s your mouth that is untouched, so how can we use the cells of the mouth to heal severe burn victims? That’s what I plan to find out.”

A preservative with a punch

“Don’t brush your teeth for three weeks.”

Strange advice coming from a dentist, but it’s all part of a unique research project led by Yvonne Kapila.

The U-M dentistry professor advises scores of paid volunteers to avoid their toothbrush for 21 days—an approach that could help answer a variety of questions related to oral health. Half of the volunteers simply gargle with a water rinse each day, while others swish around an oral rinse containing nisin. A common food preservative used in processed cheese, meats and beverages, nisin also is believed to prevent tooth decay.

“We want to see how both groups of people react to a 21-day period without brushing,” she said. “Can nisin really help prevent gingivitis?”

Kapila has focused much of her recent research efforts on the popular food preservative approved safe for human consumption decades ago by the World Health Organization and the U.S. Food and Drug Administration.

An antibacterial agent, nisin alters cell properties in bacteria to render them harmless. And since it’s been shown to reduce inflammation, Kapila is interested to see whether nisin could moonlight in everyday oral health products like mouthwash and toothpaste. GlaxoSmithKline funded a two-year study to help Kapila answer that question.

“What’s really important in the oral cavity is biofilm,” she said. “Bacteria live in these communities, and while a lot of popular mouth rinses are somewhat effective, they run into a problem trying to penetrate through biofilm. Think of nisin as a lawnmower in that it can remove the really nasty bacteria from the outer layer of the biofilm, while leaving behind the lower, healthy layers.”

"Nisin is a perfect example of a unique new therapy because it has been used safely in humans for many years, and now the lab studies support its ability to fight cancerous tumors,” Kapila said.

Kapila also is interested in nisin’s potential as a therapeutic agent for oral cancer, a leading cause of death worldwide. Survival rates have failed to improve in decades, so scientists like Kapila are looking outside the box for new cancer therapies.

“Nisin is very unique in that it uses multiple components of its structure, so it’s very difficult for bacteria to become resistant,” said Kapila, who received the International Association for Dental Research’s 2014 Innovation in Oral Care Award for her nisin studies. “For three weeks, we gave nisin to mice that had tumors and it helped prevent tumor growth. Nisin is a perfect example of a unique new therapy because it has been used safely in humans for many years, and now the lab studies support its ability to fight cancerous tumors.”

 

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