Graphic from the University of Michigan School of Dentistry (Regenerative Dentistry, Bottino Lab)
Graphic from the University of Michigan School of Dentistry (Regenerative Dentistry, Bottino Lab)

The future of general dentistry is incubating right now in and around a sterile laboratory and a unique BioPrinting platform headquartered at the University of Michigan School of Dentistry (UMSoD).

From the exterior, the dental school building, dedicated in 1971, doesn’t give a hint that it houses a futuristic research hub. The school itself, of course, dates back to 1875.

But looks can be deceiving.  

Led by Marco C. Bottino, DDS, MSc, PhD, FADM, associate professor and principal investigator, a team consisting of postdoctoral researchers, a lab specialist, two visiting faculty members, and several graduate and postgraduate students, are working to rewrite the rules of general dentistry for the remainder of the 21st Century.

Moreover, their timetable for effecting these tectonic changes will be counted in years, not decades.

 

Dr. Marco C. Bottino, Director, Regenerative Dentistry Postgraduate Program
Dr. Marco C. Bottino, Director, Regenerative Dentistry Postgraduate Program

 

Dr. Bottino jokes that he and his colleagues sometimes refer to their work as Pulp Fiction

The top-rated UMSoD offers one of the few regenerative dentistry programs in the world – and the first and only comprehensive postgraduate training within this space in the United States. Begun in August 2017, when Dr. Bottino was recruited from the Indiana University School of Dentistry, the UMSoD program is now in its infancy.

But Dr. Bottino’s regenerative dentistry group is a precocious and rapidly growing ‘toddler’ – already making important strides in its plan to use engineering tools and human stem cells to regenerate dental, oral, and craniofacial tissues. Much later, but likely still in the professional lifetimes of most of today’s working dentists, will come the routine ability for dentists to reconstruct dental tissues lost by trauma or disease.

 

Research, Clinical and Classroom Study

“It is like dental science fiction,” acknowledges Dr. Bottino, who jokes that he and his colleagues sometimes refer to their work as “Pulp Fiction,” a play on the Oscar-nominated 1994 American crime film written and directed by Quentin Tarantino.

In fact, the tooth’s pulp – or endodontium – is one area where Dr. Bottino and other regenerative dentistry researchers and clinicians are seeing promising results using different types of bioactive ingredients – including a patient’s own stem cells – to recreate the dental pulp, a highly vascularized and innervated soft tissue responsible for several important functions including temperature and pressure sensations, that has been damaged or destroyed by trauma or disease.

With partial funding from the National Institutes of Health, Dr. Bottino’s laboratory is currently exploring how to bring a tooth back to life after it’s been devitalized following a root canal.

The postgraduate students in Dr. Bottino’s one-year regenerative dentistry program receive training and insights into all the nuances of the emerging interdisciplinary field, including research, clinical, and classroom study.

The first class, which began on September 1, will run through August 31, 2019. The second 12-month class is scheduled to begin in January 2019.

Core courses for the students who enroll in the UMSoD regenerative dentistry program cover the nuts and bolts of stem cell biology, biomaterials, and biofabrication. A full-year research project provides hands-on experience, and the postgraduates are encouraged to present their findings at national American Association for Dental Research meetings and other academic venues. 

For now, Dr. Bottino, who is president-elect of the Dental Materials Group of the International Association for Dental Research (IADR), is confining total enrollment for each of the two annual UMSoD sessions to four students. While dentists are encouraged to apply for the highly specialized postgraduate training, the program also expects to attract those with an interest in the physical sciences (engineering-related), pharmacy, medicine, and veterinary medicine.

Students who complete the program will receive a Postgraduate Certificate of Completion. For more information on the applications process, please visit: https://bit.ly/2Qjcea8

Although early in its development, the UMSoD program is already attracting strong interest both from prospective students in North America, as well as international applicants.

Indeed, research and application of regenerative dentistry – as limited as it is thus far – it taking place around the globe, with scientists often working in close cooperation.

 

Bringing Teeth Back from the Dead

For example, Dr. Bottino has collaborated closely and published research along with Misako Nakashima, PhD, who heads the Department of Stem Cell Biology and Regenerative Medicine at the National Center for Geriatrics and Gerontology Research Institute in Japan. In a recent report, published in Stem Cell Research & Therapy, Dr. Nakashima and her colleagues reported unprecedented success in a pilot clinical study to assess the safety, potential efficacy, and feasibility of autologous transplantation of mobilized dental pulp stem cells (MDPSC) in pulpectomized teeth.

 

Misako Nakashima, PhD
Misako Nakashima, PhD

Five patients with irreversible pulpitis received MDPSC transplantation and subsequently were monitored for up to 24 weeks. The MDPSCs were isolated from discarded teeth.

As Dr. Misako reported:

“The electric pulp test of the pulp at 4 weeks demonstrated a robust positive response. The signal intensity of magnetic resonance imaging of the regenerated tissue in the root canal after 24 weeks was similar to that of normal dental pulp in the untreated control.”

Separately, Dr. Bottino points to the limited, but well-established, use of regenerative dentistry by endodontists to treat the permanent teeth of young patients where the pulp has died due to caries or trauma, leaving the children with a tooth or teeth where the root is not fully formed.

The procedure uses endogenous, i.e., a patient’s own stem cells and biomolecules, to save and help restore the children’s teeth. Its success depends on a multitude of factors, Dr. Bottino notes, including the patient’s systemic health. When the procedure does work, the young patients who could feel no sensation in the tooth or teeth have it restored and are able to evidence new tissue formation.

 

Regulatory Hurdles

For all the promise and early applications, progress in bringing regenerative dentistry into the mainstream of the profession is proceeding more slowly than comparable advances in medicine. One explanation is that health regulators, such as the Food and Drug Administration, still require substantial scientific evidence to move stem cell therapy for dental, oral, and craniofacial tissue regeneration.

Regardless of the obstacles, Dr. Bottino forecasts that great progress will be made in regenerative dentistry and its clinical applications over the next five to ten years.

“We are now closer than ever before to seeing dentists utilize procedures that will be much more reliable and predictable than what we do now,” he says.

As for predicting how long it will be before general dentists routinely will be able to help their patients regrow whole teeth, Dr. Bottino admits, “I’m not sure that we can have that ready in five years.”

But the day will come, he’s confident, and what now remains only “pulp fiction” will likely in our lifetimes be run of the mill.

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