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Get a Filling or Print A New Smile?

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Twinges. Painful teeth. About one in 10 people suffer from dental sensitivity caused by worn enamel. But rather than providing short-term solutions like special toothpastes or fillings, new techniques could print whole new layers of enamel onto teeth – or even stimulate the body to grow new ones.

Dr Antonios Anastasiou wants to be able to print you a new tooth. He’s not there yet, but a collaboration of material scientists, laser engineers and clinicians at the University of Leeds in the UK, have reached an important milestone along the way. They can print new layers of enamel onto the surface of teeth, preventing the exposure of tiny holes called dentine tubules, that can cause wincing sensitivity to hot and cold as well as become breeding grounds for the bacteria that cause cavities.

Right now, the materials that dentists use to repair enamel can’t provide more than a temporary fix. They fade with time and leave voids that bacteria can get to.

The technology being explored by Dr Anastasiou should overcome these problems.

“We use a material similar to the natural mineral of teeth like hydroxyapatite or some other type of calcium phosphate,” Dr Anastasiou explained.

That new material can be printed onto teeth using a femtosecond laser, which heats up small iron oxide nanoparticles in the material to bond it to the existing dental surface. The small heating area avoids damaging the surrounding tooth. They can also add cerium and other exotic elements to the mix to give the new material antibacterial properties.

“What we are doing is figuring out how to prevent bacteria from colonising the surface.” – Dr Antonios Anastasiou, University of Leeds, UK

“Not only can we restore enamel with a material similar to the original mineral of teeth, we can also improve it. What we are doing is figuring out how to prevent bacteria from colonising the surface,” said Dr Anastasiou.

His solution is also longer lasting. While current restoration materials like resins can shrink over time or with temperature, his material does not. It is also a material that makes it easy for gums to reattach to, helping to prevent an infection of the gums around the mouth known as periodontitis.

Right now, the technique is being trialled as an appliance in dental schools to make sure that there are no long-term side effects and that it can hold up to the rigours of daily life.

“Some patients have it in their mouth and are taking care of it, brushing it, and having it on during eating. If these tests are positive then we can go on to clinical studies,” he said.

Sensitivity

Ultimately, the printed enamel could be out in the marketplace in about five years and could help those who suffer from worn enamel enjoy hot and cold drinks without sensitivity.

“One of our professors said that he got into the research because he wanted to enjoy his whisky with ice,”
Dr Anastatiou joked.

Printing tooth repairs is one thing, but what if your body could be stimulated to regrow a tooth that is lost or damaged?

That’s the aim of Dr Igor Adameyko from the Medical University of Vienna, Austria, who is trying to uncover the secret of how to induce the formation of new teeth using stem cells.

But to do that, he first needed a map.

“For a long time, nobody knew how many cell types and subtypes live in teeth. This knowledge is essential to understand how this organ is developing, growing, and maintaining itself,” said Dr Adameyko.

To undertake such a cell census, he used a process known as single-cell transcriptomics. This new method can break down cells one by one, measuring the RNA – a key molecule similar to DNA that controls which genetic instructions are put into action – of thousands of cells at the same time.

By examining the RNA blueprint of a cell, researchers can figure out what its type and function is. Through that painstaking process, the team has built up an atlas of all the cell types that live in teeth which have also helped him understand how different types of cells interact.

‘Cells exchange signals and these are not some kind of ethereal signals, but quite material. Molecules are made and secreted, and some cells have receptors that can bind to these molecules. We can actually see these pairs in the data set and predict these interactions,’ he said.

Glial cells

Armed with that knowledge, his team has honed in on what controls the life and death of a tooth, as well as what controls the conversion of cells known as glial cells, a type of cell that surrounds and insulates neurons, into dental stem cells that can grow teeth.

Teeth originate from two different types of embryonic tissue – epithelia, which generates cells producing enamel, and mesenchyme which can become bone or the living tissue inside the tooth which is called dental pulp.

Dr Adameyko and his team have also been investigating dental development and regeneration in mice, whose teeth grow throughout their lives because they feed on hard food. Using special chemical manipulation they made the mice’s teeth transparent and watched what happened to the tracked glial cells.

Such knowledge could help the team figure out how to activate glial cells to convert into new stem cells in humans, to grow new roots for regenerating live teeth or crafting a new nerve for a dental implant.

“If this exists in human teeth, by doing this we will be able to find some molecules that strengthen the tooth’s reparative response,” Dr Adameyko said.

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Ibuprofen, Acetaminophen More Effective Than Opioids In Treating Dental Pain

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Opioids are not among the most effective — or longest lasting — options available for relief from acute dental pain, a new examination of the results from more than 460 published studies has found.

Ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) alone or in combination with acetaminophen are better at easing dental pain, according to new research conducted with the School of Dental Medicine at Case Western Reserve University.

The study examining relief of acute pain in dentistry — recently featured on the cover of The Journal of the American Dental Association — evaluated the safety and efficacy of dozens of pain-relief options.

“What we know is that prescribing narcotics should be a last resort,” said Anita Aminoshariae, an associate professor in the dental school’s Department of Endodontics and one of the study’s authors.

Each day, more than 115 Americans die as a result of an opioid overdose, according to the National Institutes of Health.

“No patient should go home in pain,” Aminoshariae said.

“That means that opioids are sometimes the best option, but certainly should not be the first option.”

Aminoshariae said the goal of the systematic review was to summarize data — using five in- depth studies — of the effectiveness of oral-pain medications.

“The best available data suggests that the use of nonsteroidal medications, with or without acetaminophen, offers the most favorable balance between benefits and harms, optimizing efficacy while minimizing acute adverse events,” she said.

She cited the national opioid epidemic as one of many reasons why health-care providers should take note of the findings.

The research found that, for adults, a combination of 400 milligrams of ibuprofen and 1,000 milligrams of acetaminophen was superior to any opioid-containing medications studied.

“Our aim was to create a compendium detailing both the benefits and harms of these medications as a resource for dentists to use in their clinical decision-making,” Aminoshariae added.

The study also found that opioids or drug combinations that included opioids accounted for the most adverse side effects — including drowsiness, respiratory depression, nausea/vomiting and constipation — in both children and adults.

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Gum Disease May Be A Key Initiator Of Rheumatoid Arthritis Related Autoimmunity

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The results of a study presented at the Annual European Congress of Rheumatology (EULAR 2018) demonstrates increased levels of gum disease, and disease-causing bacteria, in individuals at risk of rheumatoid arthritis (RA).

“It has been shown that RA-associated antibodies, such as anti-citrullinated protein antibodies, are present well before any evidence of joint disease. This suggests they originate from a site outside of the joints,” said Dr Kulveer Mankia of Leeds Institute of Rheumatic and Muscoskeletal Medicine and the Leeds Biomedical Research Centre (study author).

“Our study is the first to describe clinical periodontal disease and the relative abundance of periodontal bacteria in these at-risk individuals. Our results support the hypothesis that local inflammation at mucosal surfaces, such as the gums in this case, may provide the primary trigger for the systemic autoimmunity seen in RA.”

Rheumatoid arthritis is a chronic inflammatory disease that affects a person’s joints, causing pain and disability. It can also affect internal organs. Rheumatoid arthritis is more common in older people, but there is also a high prevalence in young adults, adolescents and even children, and it affects women more frequently than men.

The prevalence of gum disease is increased in patients with RA and could be a key initiator of RA-related autoimmunity. This is because autoimmunity in RA is characterised by an antibody response to citrullinated proteins and the oral bacterium Porphyromonas gingivalis (Pg) is the only human pathogen known to express an enzyme that can generate citrullinated proteins.

“We welcome these data in presenting concepts that may enhance clinical understanding of the key initiators of rheumatoid arthritis,” said Professor Robert Landewé, Chairperson of the Scientific Programme Committee, EULAR.

“This is an essential step towards the ultimate goal of disease prevention.”

In results from the study, dentists diagnosed clinical gum disease in significantly more at-risk individuals than in healthy controls (73% vs. 38%, p=0.02). In addition, the percentage of sites with clinical attachment level (CAL) ?2mm, pocket depth (PD) ?4mm, bleeding on probing (BOP), periodontal disease (PDD), and active periodontal disease (PDD+BOP), were all significantly greater in the at-risk individuals compared to controls (p<0.05). In non-smokers, PDD and active PDD were more prevalent in at-risk individuals compared to controls.

DNA was isolated from the subgingival plaque, next to the gums, of each participant and used to measure the levels of three types of bacteria, Pg, Aggregatibacter actinomycetemcomitans (Aa) and Filifactor Alocis. Results showed that there was increased abundance of both Pg and Aa in at-risk individuals. However, in at-risk individuals, only Pg was significantly increased at healthy dental sites and was associated with the overall extent of gum disease (p<0.001).

The study included 48 at-risk individuals (positive test for anti-citrullinated protein antibodies, musculoskeletal symptoms but no clinical synovitis), 26 patients with RA and 32 healthy controls. The three groups were balanced for age, gender and smoking. At-risk individuals underwent ultrasound assessment to assess for subclinical synovitis; only two (4%) were found to have ultrasound synovitis. Dentists examined six sites per tooth in each participant and a clinical consensus was agreed in each by three dentists.

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Cellular Messengers Communicate With Bacteria In The Mouth

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A new UCLA-led study provides clear evidence that cellular messengers in saliva may be able to regulate the growth of oral bacteria responsible for diseases, such as periodontitis and meningitis.

The study’s findings, which suggest that a body’s cellular messengers play an important role in managing the amount of good and bad bacteria in the mouth, are published online and will appear in the May issue of the Journal for Dental Research.

Study authors Dr. David Wong, professor of oral biology and associate dean for research at the UCLA School of Dentistry, and Dr. Wenyuan Shi, chief executive officer and chief science officer at the Forsyth Institute, an oral health research institute in Cambridge, Massachusetts, asked the question of whether our RNA — the cellular messengers — can communicate with harmful bacteria in the mouth.

RNA acts as a messenger that transports DNA’s instructions to other parts of the cell. Small regulatory noncoding RNAs, known as sRNAs, regulate our genes. A new class of sRNAs has also been discovered called tsRNA, which is transfer RNA-derived small RNA. tsRNA is found in human body fluids, including blood, tears and saliva.

The research team began by analyzing salivary sRNAs and found many of them belong to tsRNA with their sequences matching the partial transfer RNA sequences of several Gram-negative oral bacteria — bacteria that have a highly toxic outer layer that can cause periodontal disease. These salivary tsRNAs could potentially affect bacterial tRNA, a type of RNA molecule that helps decode a messenger RNA sequence into a protein and is required for bacterial growth. The Gram-negative bacterium used in the study to test this hypothesis was Fusobacterium nucleatum (F. nucleatum), the bacteria responsible for periodontitis.

The team showed that host cells respond to the presence of F. nucleatum by releasing specific tsRNA with sequence matching to tRNA of F. nucleatum. Furthermore, these released tsRNAs can inhibit the growth of F. nucleatum, but they have no effect on the growth of Gram-positive oral bacteria, such as Streptococcus mitis, a bacterium that responds to antibiotics.

“This study establishes that there is a clear channel of communication between RNA messengers and bacteria in our mouth,” said Wong, who holds the Felix and Mildred Yip Endowed Chair in Dentistry.

“Furthermore, we have shown that these messengers may play an important role in mediating interactions between bacteria and their host.”

Another significant study finding was the majority of tRNA bacteria sequences that show high sequence similarity with salivary tsRNAs came from antibiotic-resistant Gram-negative bacteria. This observation could lead to a better understanding of the mechanisms behind the growth of oral bacteria, resistance to antibiotics, and in-turn oral diseases, Wong said.

“Our findings could lead to new therapies to treat diseases caused by harmful bacteria,” said Shi, a former professor of oral biology at the UCLA School of Dentistry.

“As a convener for oral health and biotech experts, Forsyth is thrilled about collaborating with UCLA on this exciting research.”

For example, one of the hallmarks of periodontitis is a shift from mostly Gram-positive bacteria to mostly Gram-negative bacteria. With a better understanding of how Gram-negative bacteria grow, perhaps there is potential to reverse the growth or even kill Gram-negative bacteria.

“Our finding could potentially open a new door for prevention and treatment of periodontal diseases” said Dr. Xuesong He, a researcher at the Forsyth Institute and the co-first author on this study.

Additional co-authors of the research include Batbileg Bor and Lujia Cen, both from the Forsyth Institute; Feng Li, Kikuye Koyano, Xinshu “Grace” Xiao and Feng Li from Hunan University of Chinese Medicine. Feng Li also conducts research at the UCLA School of Dentistry.

This research was supported by grants from the National Institute of Dental and Craniofacial Research and from the National Institutes of Health.

Wong is co-founder of RNAmeTRIX Inc., a molecular diagnostic company. He holds equity in RNAmeTRIX and serves as a company director and scientific advisor. The University of California also holds equity in RNAmeTRIX. Intellectual property that David Wong invented and which was patented by the University of California has been licensed to RNAmeTRIX. Wong also is a consultant to GlaxoSmithKline, PeriRx, Wrigley and Colgate-Palmolive. Shi is the founding scientist of C3J Therapeutics, Inc., which has licensed technologies from UC Regents that could be indirectly related to this research project.

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