by Katie Griffith

From cyclic forces to stem cells, Jeremy Mao, DDS, PhD, is advancing the science of orthodontics

Pittsburgh is a special place for orthodontist Jeremy Mao, DDS, PhD. It was there, at the University of Pittsburgh, that experiments on cyclic forces and stem cells began to carve the path of Mao’s academic career. At Pitt, he began a combined research and clinical career that has led to more than 50 patents covering the regeneration of facial and dental tissues, dermal tissues, orthopedic tissues, and the science behind OrthoAccel Technologies’ new AcceleDent product.

AcceleDent is a removable dental device that orthodontic patients wear in the mouth for 20 minutes daily. It generates a microvibration force designed to modulate the bone tissue remodeling process and accelerate orthodontic tooth movement. The device is hands-free so that users can carry out most routine tasks during the 20-minute session.

Work on the science behind the AcceleDent system began with Mao’s discovery that the use of cyclic forces can accelerate bone remodeling.

“The device is based on a principle that is not difficult to explain, although it took several years to figure out,” Mao says.

How AcceleDent Works

Mao explains that the orthodontist is able to move teeth around not so much because of the teeth, but because of the bone surrounding teeth. The science behind AcceleDent takes advantage of this to speed up orthodontic treatment.

“You have to be able to induce bone resorption and bone formation to get teeth to move,” Mao says. Bone resorption creates the space for teeth to move, while bone formation fills the gap behind the tooth. According to Mao, “The concept of AcceleDent is based on the scientific principle that with cyclic forces there is more bone remodeling.”

Jeremy Mao, DDS, PhD

Jeremy Mao, DDS, PhD

Cyclic forces generate the vibration of the AcceleDent system. The vibration generates multiple cycles of stimuli to cells of both osteoblasts, which create bone; and osteoclasts, which break down bone tissue. This is how bone remodeling is sped up.

Current orthodontics utilize static force (such as rubber bands and coils), which apply one stimulus to the cells. With cyclic forces, there are multiple stimuli to the cells. The cells respond to dynamic signals, and in response they get involved with these bone-remodeling and bone-resorbing activities.

After Mao and his research team uncovered these effects of cyclic forces on tooth movement, they patented the science (by then, Mao was in Chicago). OrthoAccel, at that time a startup company, licensed the patent. According to Mao, an incubation process followed in which the concept was developed into the AcceleDent product.

OrthoAccel completed a Phase I Human Clinical Trial of AcceleDent at the University of Texas Dental Branch in Houston, finding that the device is safe and effective. Mao was not involved in the trial. OrthoAccel has obtained approval for the AcceleDent system from the European Union and from Australia’s Therapeutic Goods Administration. OrthoAccel is currently anticipating the conclusion of a pivotal trial for FDA clearance in the United States.

Regenerating a TMJ with Stem Cells

As Mao’s research work on cyclic forces was winding down, his efforts in stem cell research were beginning to show big results. By this time Mao had taken up a spot with the University of Illinois at Chicago. There, in 2003 and 2004, Mao and his research team discovered that a TMJ could be regenerated from stem cells.

“When you take stem cells from any of the sources (bone marrow, adipose tissue, or dental pulp) and differentiate these cells into cartilage cells and bone cells, you can start thinking about regenerating a whole joint,” Mao says.

According to Mao, who was then recruited by Columbia University in New York, teeth are a rich source of stem cells. His lab takes teeth that are sent in (usually from children who lose a tooth, extractions for orthodontic work, or wisdom teeth) and place them in a clean environment. The teeth are then opened to expose the pulp, which is removed and digested with enzyme so that the stem cells can be freed from the extracellular matrix where they were previously trapped. “And from those cells you just have to be able to pick the stem cells,” Mao says. “It’s a fairly well-established process.”

Stem Cells and Orthodontics

In addition to reconstructing whole TMJs from stem cells, Mao has other ideas of where stem cell research could someday improve the practice of dentists and orthodontists. For example, a large portion of dentistry deals with the loss of teeth.

“I believe the periodontal bone tissue, pulp of the teeth, and even a whole tooth can be regenerated by stem cells and related technologies,” Mao says.

“However, to do this, in addition to stem cells, one would need tissue engineering, bioengineering, biomaterials, and to direct the cells to differentiate into the cells we want.” Science would also need to develop a way to provide the anatomic shape of the desired structures. Mao currently has regeneration projects going on all of these fronts at Columbia University.

When contemplating the possibility of regenerating an entire mouth of teeth, the complexity and cost of the undertaking are the first big setbacks. “It may well be cost-prohibitive,” Mao says. “However, like many new technologies, as the technology matures the cost will come down. I see that there is a potential for this, but not in the near future.”

Automated Orthodontics

When discussing the future of orthodontics, Mao sees AcceleDent and other, more automated, technologies paving the way. “The demand of increasingly automated appliances (Invisalign as an example) has taken some of the more detailed orthodontic work away from the orthodontist and made it more automated,” he explains.

To read more articles by and about Mao, in our online archives.

Although both products are based on the principle of making orthodontics more automated, “AcceleDent and Invisalign are very different devices. Invisalign would address a small percentage of the orthodontic cases, but as anticipated by OrthoAccel, the AcceleDent would address the majority of orthodontic cases,” he says.

Mao anticipates that the trend toward automation will continue to grow in the future, and that orthodontists may appreciate their role as “Q & A person” to make sure the teeth are moving in the right direction.

The goal of all this science, Mao concludes, is not just to automate the process but “to improve the quality of orthodontics.”

Katie Griffith is a contributing writer for Orthodontic Products. For more information, contact /em>