Biomaterial could keep tooth alive after root canal (video)

A root canal ranks high on most people's list of dreaded dental procedures. Although the lengthy and sometimes painful surgery relieves the agony of an infection, a root canal results in a dead tooth with no living soft tissue, or dental pulp, inside. Today, scientists report development of a peptide hydrogel designed to stimulate the growth of new blood vessels and dental pulp within a tooth after the procedure. The researchers are presenting their results today at the 256th National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world's largest scientific society, is holding the meeting here through Thursday. It features more than 10,000 presentations on a wide range of science topics.
A brand-new video on the research is available at http://bit.ly/acsrootcanal.
"What you end up with after a root canal is a dead tooth," Vivek Kumar, Ph.D., the project's principal investigator, says. "It's no longer responsive. There are no nerve endings or vascular supply. So the tooth is very susceptible to subsequent infection and, ultimately, falling out."
During a root canal, the dentist drills off the top of an infected tooth to access the soft tissue inside. The dentist then removes the infected dental pulp and fills the space with tiny rubber rods called gutta percha and caps the repaired tooth with a crown.
Kumar and Peter Nguyen, Ph.D., who is presenting the work at the meeting, wanted to develop a material that could be injected in place of the gutta percha. The material would stimulate both angiogenesis, or new blood vessel growth, and dentinogenesis, or proliferation of dental pulp stem cells, within the tooth. Both Kumar and Nguyen are at the New Jersey Institute of Technology.
Kumar drew on his previous experience developing a hydrogel that stimulates angiogenesis when injected under the skin of rats and mice. The hydrogel, which is liquid during injection, contains peptides that self-assemble into a gel at the injection site. The peptides contain a snippet of a protein called vascular endothelial growth factor, which stimulates the growth of new blood vessels. Kumar, then a postdoctoral researcher at Rice University, and his coworkers showed that the self-assembling peptide hydrogel stimulated angiogenesis and persisted under the rodents' skin for as long as three months.
"We asked the question, if we can stimulate angiogenesis in a limb, can we stimulate angiogenesis in other regions that have low blood flow?" Kumar says. "One of the regions we were really interested in was an organ in and of itself, the tooth." So Kumar and Nguyen added another domain to the self-assembling angiogenic peptide: a piece of a protein that makes dental pulp stem cells proliferate.
When the team added the new peptide to cultured dental pulp stem cells, they found that the peptide not only caused the cells to proliferate, but also activated them to deposit calcium phosphate crystals -- the mineral that makes up tooth enamel. However, when injected under the skin of rats, the peptide degraded within one to three weeks. "This was shorter than we expected, so we went back and redesigned the peptide backbone so that we currently have a much more stable version," says Kumar.
Now, the team is injecting the peptide hydrogel into the teeth of dogs that have undergone root canals to see if it can stimulate dental pulp regeneration in a living animal. If these studies go well, the researchers plan to move the hydrogel into human clinical studies. They have filed a patent for the redesigned peptide.
The hydrogel in its current form likely won't reduce the invasiveness or pain of a root canal, but Kumar and Nguyen are planning future versions of the peptide that contain antimicrobial domains. "Instead of having to rip out everything inside the tooth, the dentist could go in with a smaller drill bit, remove a little bit of the pulp and inject our hydrogel," Kumar says. The antimicrobial portion of the peptide would kill the infection, preserving more of the existing dental pulp, while helping grow new tissue. And the root canal may no longer be such a dreaded procedure.
A press conference on this topic will be held Wednesday, August 22, at 9 a.m. Eastern time in the Boston Convention & Exhibition Center. Reporters may check-in at the press center, Room 102 A, or watch live on YouTube http://bit.ly/ACSLive_Boston2018. To ask questions online, sign in with a Google account.

Bioengineered tooth replacement opens doors to new therapies

Tooth loss is a significant health issue currently affecting millions of people worldwide. While artificial dental implants are the existing standard tooth replacement therapy, they do not exhibit many properties of natural teeth and can be associated with complications leading to implant failure. Two articles published in the September 2018 issue of the Journal of Dental Research share recent advances in bioengineering teeth.

In the article "Bioengineered Tooth Buds Exhibit Features of Natural Tooth Buds" Pamela Yelick, Tufts University School of Dental Medicine, Boston, Mass., USA and co-authors explored new methods to create highly cellularized bioengineered tooth bud constructs that include features that resemble natural tooth buds such as the dental epithelial stem cell niche, enamel knot signaling centers, transient amplifying cells and mineralized dental tissue formation. The constructs were composed of postnatal dental cells encapsulated within a hydrogel material that were implanted subcutaneously into immunocompromised rats.

This is the first report that describes the use of postnatal dental cells to create bioengineered tooth buds that exhibit evidence of these features of natural tooth development, pointing to future bioengineered tooth buds as a promising, clinically relevant tooth replacement therapy.

In the article "Bone Marrow Stromal Cells Promote Innervation of Bioengineered Teeth" Sabine Kuchler-Bopp, French National Institute of Health and Medical Research and Fédération de Médecine Translationnelle de Strasbourg, France, and co-authors developed a strategy where autologous mesenchymal cells coming from bone marrow can be used to supply nerves to bioengineered teeth without treatment that uses an immunosuppressor. The innervation of teeth is essential for their function and protection but does not occur spontaneously after injury. This new method provides innervation while avoiding multiple side effects associated with immunosuppressors.

"These exciting studies point to a promising future for bioengineered teeth," said Journal of Dental Research Editor-in-Chief William V. Giannobile. "This cutting-edge research has the potential to advance tooth replacement therapy and the science base to bring such regenerative medicine treatments to improve clinical care."

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Dental care may benefit patients scheduled for cancer surgery

Preoperative oral care by a dentist may help reduce postoperative complications in patients who undergo cancer surgery, according to a new BJS (British Journal of Surgery) study.

Of 509,179 patients studied, 16% received preoperative oral care from a dentist. When a surgeon requested that a dentist provide preoperative oral care to a patient with cancer, the dentist checked the patient's oral condition, provided professional tooth cleaning, taught the patient self-cleaning methods for the teeth, and provided any treatment needed.

In the study, 15,724 patients (3.09%) developed postoperative pneumonia and 1734 (0.34%) died within 30 days of surgery. After adjustments, preoperative oral care by a dentist was linked with a decrease in postoperative pneumonia (3.28% versus 3.76%) and death within 30 days (0.30% versus 0.42%).

"The findings could help improve strategies for the prevention of postoperative complications," the authors wrote.

Unwise opioids for wisdom teeth: Study shows link to long-term use in teens and young adults

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Getting wisdom teeth removed may be a rite of passage for many teens and young adults, but the opioid painkiller prescriptions that many of them receive could set them on a path to long-term opioid use, a new study finds.

Young people ages 13 to 30 who filled an opioid prescription immediately before or after they had their wisdom teeth out were nearly 2.7 times as likely as their peers to still be filling opioid prescriptions weeks or months later, according to new research from a University of Michigan team.

Those in their late teens and twenties had the highest odds of persistent opioid use, compared with those of middle school and high school age, the researchers report in a research letter in the new issue of JAMA.

Led by Calista Harbaugh, M.D., a U-M research fellow and surgical resident, the researchers used insurance data to focus on young people who were 'opioid naïve' -- who hadn't had an opioid prescription in the six months before their wisdom teeth came out, and who didn't have any other procedures requiring anesthesia in the following year.

"Wisdom tooth extraction is performed 3.5 million times a year in the United States, and many dentists routinely prescribe opioids in case patients need it for post-procedure pain," says Harbaugh, a National Clinician Scholar at the U-M Institute for Healthcare Policy and Innovation. "Until now, we haven't had data on the long-term risks of opioid use after wisdom tooth extraction. We now see that a sizable number go on to fill opioid prescriptions long after we would expect they would need for recovery, and the main predictor of persistent use is whether or not they fill that initial prescription."

Other factors also predicted risk of long-term opioid use. Teens and young adults who had a history of mental health issues such as depression and anxiety, or chronic pain conditions, were more than others to go on to persistent use after filling their initial wisdom tooth-related prescription.

More about the study

In all, 1.3 percent of 56,686 wisdom tooth patients who filled their opioid prescription between 2009 and 2015 went on to persistent opioid use, defined as two or more prescriptions filled in the next year written by any provider for any reason. That's compared with 0.5 percent of the 14,256 wisdom tooth patients who didn't fill a prescription.

Though those numbers may seem small, the high number of wisdom teeth procedures every year mean a large number of young people are at risk, notes Harbaugh, a research fellow with the Michigan Opioid Prescribing and Engagement Network, or Michigan OPEN.

The team used data from employer-based insurance plans, available through the Truven MarketScan database purchased for researchers' use by IHPI. Chad Brummett, M.D., co-director of Michigan OPEN, is senior author of the new research, and the team includes U-M School of Dentistry professor Romesh Nalliah, D.D.S., MHCM.

The data show opioid prescriptions filled, but not actual use of opioid pills by patients. Leftover opioids pose a risk of their own, because they can be misused by the individual who received the prescription, or by a member of their household or a visitor. The researchers also couldn't tell the reason for the later opioid prescription fills by those who went on to persistent use.

The authors suggest that dentists and oral surgeons should consider prescribing non-opioid painkillers before opioids to their wisdom tooth patients. If pain is acute, they should prescribe less than the seven-day opioid supply recently recommended by the American Dental Association for any acute dental pain.

"There are no prescribing recommendations specifically for wisdom tooth extraction," says Harbaugh. "With evidence that nonsteroidal anti-inflammatories may just as, if not more, effective, a seven-day opioid recommendation may still be too much."

Brummett adds, "These are some of the first data to the show long-term ill effects of routine opioid prescribing after tooth extractions. When taken together with the previous studies showing that opioids are not helpful in these cases, dentists and oral surgeons should stop routinely prescribing opioids for wisdom tooth extractions and likely other common dental procedures."

Importance for patients and parents

Getting a prescription for an opioid painkiller around the time of a wisdom tooth procedure comes with many decision points, Harbaugh says.

"Patients must decide whether to fill the prescription and take the medication, and where to store and dispose of the unused pills. All of these decision points need to be discussed with patients," she says. "Patients should talk to their dentists about how to control pain without opioids first. If needed, opioids should only be used for breakthrough pain, as backup if the pain's not controlled with other medications."

The Michigan-OPEN team is currently studying the wisdom tooth extraction population further, by speaking with patients and parents about their experience and how many opioid pills they actually took. This will allow them to create evidence-based prescribing guidelines just like the ones they've developed for other operations.

The research was funded by the federal Substance Abuse and Mental Health Services Administration, the Michigan Department of Health and Human Services, and the University of Michigan Precision Health Initiative.