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In Vivo
Dental Medicine

Engineering Dental Research

When news media reported last year that Jeremy Mao’s research team had created a breast
Jeremy Mao
Jeremy Mao
implant from stem cells, few noted that Dr. Mao is a dentist. Though Dr. Mao (who has a D.D.S. and a Ph.D.) spends less time treating patients, his career as a tissue engineer exemplifies a growing trend in dental research, particularly at the College of Dental Medicine. Research increasingly shows that oral health is entwined with general health and that dental research can bring benefits to a wide array of medical fields. Dr. Mao, who recently joined the College of Dental Medicine from the University of Illinois at Chicago, took a break from his busy schedule to talk with InVivo.

What connection does your stem cell work have to dentistry?

A lot, actually. My lab got into that mostly by serendipity, because the same stem cells that we used previously to make the bone and cartilage in an engineered temporomandibular joint (TMJ) can also make adipose tissue. When we were trying to engineer the joint, we also turned these human stem cells into fat cells. People asked us, ‘why make fat cells? most people are trying to get rid of their fat cells!’ But for patients with soft tissue defects resulting from congenital disorders, trauma or tumor surgery, engineered fat tissue from stem cells has the potential to provide a replacement. Breast cancer defects can potentially be fixed from the patient’s own stem cells instead of synthetic implants.

Earlier research has used fat cells leftover from liposuction to make soft tissue implants, but these quickly shrink because the cells have limited lifespan. Implants made from stem cell-derived fat cells are long lasting, because stem cells in the implant keep replenishing the supply.

So what does this have to do with dentistry? Dentistry is much more than just the teeth. A great deal of reconstructive and plastic surgery is performed in the craniofacial region. The soft tissue and hard tissue defects that result from oral surgery or craniofacial surgery can potentially be corrected using stem cells.

The bioengineered TMJ your team created a few years ago also got a lot of media attention. How much of a health issue is this type of disease?

About 10 million people in the United States have TMJ problems and in the most severe cases they can hardly talk or chew, and must rely on a liquid diet.

Today, surgeons use bone grafts harvested from the hip or rib to repair a badly diseased TMJ. The downside is you create a secondary trauma site. Why should a patient have to sacrifice a perfectly normal rib? Sometimes metal and synthetic materials are used, but none of these, including the bone graft, are satisfactory. They break, they chip, they wear out. And they don’t work that well.

The goal of tissue engineering is to enable tissue and organ replacements to be ‘grown’ by the patient, and look and function as nature’s originals. In our lab we’ve used human stem cells and put them through steps that nature uses to grow a TMJ that has the same shape and dimensions as the original structure. Also, TMJ is a prototype for larger joints such as the knee or hip. We recently engineered a part of a human-shaped knee joint from human stem cells. We want to grow functional joints from stem cells in patients with arthritis and trauma.

Dental researchers today seem to be less confined to strictly dental issues. How did that come about?

Earlier dental research has solved some of the ‘easier’ problems in dentistry, and in the process the practice of dentistry has changed. In the 1930s and 40s cavities and tooth decay were so prevalent that most people lost some or many teeth by their teens or early 20s. That’s not the case anymore in the United States, largely because of dental research. Dentists saw that people living in areas with naturally high levels of fluoride in the water didn’t get many cavities. Based on that research, most regions started to add fluoride to drinking water. Now some people reach their 20s and beyond without any tooth decay.
But there are so many other issues that are harder to deal with, like TMJ diseases. Dental professionals realized that if we want to provide effective treatment for these individuals, we can’t do it without research and so are using modern tools like molecular biology, stem cells, and tissue engineering to advance the field.

In addition, a lot of dental research has ramifications that go far beyond dentistry. For example, gum disease may trigger cardiovascular disease. Many craniofacial disfigurations are associated with defects in other regions of the body. A cut inside the mouth heals without scarring, just like a fetal wound, whereas a cut in the skin scars. Research on macromolecules in oral mucosa may provide clues to scarless skin healing. One scientific connection between dentistry and medicine is that the same stem cells that develop into the bulk of the teeth can also develop into bone, cartilage, fat, tendons, ligaments, and even cells that form internal organs.

—Susan Conova