Regenerative Dentistry: A Lozenge To Rebuild Tooth Enamel Is Hard To Swallow
Regenerative Dentistry: A Lozenge To Rebuild Tooth Enamel Is Hard To Swallow
A lozenge to rebuild tooth enamel? Ah yes, such exciting news. And it whitens teeth as well.
First of all, it is important to separate enamel remineralisation from enamel regeneration.
Dental enamel is the hardest tissue in the body. It’s not living tissue – it’s comprised of calcium phosphate and arranged in a crystal structure known as hydroxyapatite (HA), an inorganic mineral present in human bone and teeth. Dentin is the hard tissue beneath the enamel. HA crystals make up around 70-80% of the weight of human dentin and enamel.
Although it has an important role in the structural strength of bone and teeth, it doesn’t naturally regenerate.
Unfortunately, tooth enamel can’t be artificially recreated either. But it can be remineralised.
There are toothpastes already available which do that by pushing calcium and phosphates back into the tooth, and that hardens the enamel. It works because of fluoride. Fluoride contains these minerals in the saliva that acid has drawn out, and pushes them back into the teeth.
Its overall effectiveness depends largely on attentive and routine oral hygiene because it dilutes reasonably quickly.
While fluoride can also fortify tooth enamel, it does not, nor can it actively rebuild it. While sucking on a lozenge increases saliva production, increases fluoride reabsorbtion and thereby remineralises, there seems little scientific proof that regeneration is even possible.
He received a $100,000 Amazon Catalyst grant through CoMotion, the university’s commercialisation centre, in support of the project. Key contributions were also made by Hanson Fong, a research scientist in the Department of Materials Science and Engineering.
The team’s plans also included the development of related products for use in dental clinics.
In 2021 a phase of trials were anticipated to start in March or April that year but were delayed for twelve months. Each study was expected to take two weeks, and last no more than three months. The development of an over-the-counter a toothpaste for over-the-counter use, but without an assigned launch schedule.
There were discussions with possible corporate partners about its commercial application potential, according to Professor Mehmet Sarikaya, head of the research team. He is a professor in the Department of Materials Research Science and Engineering, and adjunct professor for the Department of Oral Health Sciences. Also playing a critical role is Dr Sami Dogan of the School of Dentistry’s Department of Restorative Dentistry.
The clinical trial had three objectives: to demonstrate the efficacy; document that; and benchmarking – to see how the whitening effect compares to existing commercial treatments. Researchers tested the lozenge on live rats, and extracted human, pig, and rat teeth.
As far as the regenerative lozenge is concerned, the research team prepared to launch clinical trials containing a genetically engineered peptide, or chain of amino acids, along with phosphorus and calcium – the building blocks of tooth enamel. The peptide is derived from amelogenin, the key protein in the tooth’s crown. It is also key to the formation of cementum, which makes up the surface of the tooth root.
The lozenge design deposits several micrometres of new enamel on the teeth via the peptide, while not affecting oral soft tissue. Apparently two lozenges a day would rebuild enamel, with one a day maintaining a healthy layer.
The clinical trials were delayed for a year. Published articles read like marketing pieces that suggest positive, easy results with few concrete facts: and some of those are largely inaccurate. Teeth are the ultimate test of the veracity of any such product.
Like that tooth hypersensitivity results from weakness in the enamel, making the underlying dentin and nerves more susceptible to temperature.
Much of this work was being done by the GEMSEC lab at the University of Washington. In 2021 Professor Mehmet Sarikaya, head of the project was charged with submitting false grant documentation to the National Science Foundation, grinding a lot of the research to a halt.
The University was ordered to pay $US800,000 to settle the allegations for a highly competitive grant.
Curiously, Sarikaya had also been charged with misappropriation of funds in 1998 – same university, same Department of Materials Science and Engineering.
So there’s that.
Dentinal reaction is not the result of enamel weakness but rather enamel that no longer exists. It can also arise from damaged or receding gingival tissues. There are a number of other reasons hypersensitivity can emerge but none of them are because of ‘weak’ enamel.
Like Yoda’s “Do or do not. There is no try,” tooth enamel either exists, or it doesn’t.
Initial information on this treatment was published in 2005 in Nature magazine, credited to the FAP Dental Institute, Tokyo under the research team of Dr Kazue Yamagishi.
Dr Yamagishi and her team had the novel idea of restoring teeth that showed early decay instead of drilling and filling. What was proposed was a special toothpaste with HAP crystals: hydroxyapatite molecules that crystallise to form microscopic clumps. After etching the decaying tooth the toothpaste is applied to create a perfect seal, unlike a filling. Although the treatment was referred to as a toothpaste, it was more accurately a professional dental treatment taking about 15 minutes to complete. It seems somewhat similar to an already clinically available treatment (a caries infiltrant), only more biocompatible.
In 2016 an announcement launching the toothpaste was posted on Dr Kazue Yamagishi’s website – which was intended for the Japanese market only.
As of 2023 it’s still not an existing product; nor it does look like it will be one in the near future.
Or ever. Attempts to contact Dr Kazue Yamagishi for information have failed.
Although it’s not a product, it seems to have instigated the belief by some that there is a Japanese toothpaste that can regenerate enamel.
All that’s currently available from Japan is hydroxyapatite toothpaste – a fluoride alternative.
And it’s not new: the world’s first nanoparticle hydroxyapatite toothpaste with the brand name Apadent was introduced in the 1980s.
A decade later, hydroxyapatite was approved as an anti-caries agent; ten years after that, the particle size was reduced from 3-to-2-figure nanoscale, which increased its remineralising properties. It was the marker for toothpaste containing this compound being made available to the European and American markets.
According to the American Academy of Cosmetic Dentistry, US consumers alone spend approximately $US10 billion treating hypersensitivity via toothpastes, clinical pastes, gels, and mouthwashes; and more than $US1.4 billion on over-the-counter tooth whitening products.
Despite the expanding range of products, treatment options are limited – and hypersensitivity is still the most common cause of dental discomfort.
The complexity of enamel regeneration is a separate-layered process: enamel, dentin, pulp, and cementum.
For deep cavities, what is more crucial is dentin regeneration, not enamel.
The lozenge claims to produce enamel that is much whiter than tooth-whitening products achieve.
As a whitener, there is distinct advantage in that.
Conventional treatments rely on the bleaching agents of hydrogen peroxide, which removes discoloration by dissolving stained mineral layer from the tooth surface. This chemical-etching process is at the expense of the enamel with the underlying dentin becoming exposed because of this chemical leaching. This creates hypersensitivity, and an increased susceptibility to cavities that far outweigh any cosmetic benefit.
The American Dental Association reports that enamel erosion caused by peroxide demineralisation occurs in 64% of patients.
Gum recession and pulp inflammation are also the documented adverse affects of regularly using whitening products.
What could be possible with the lozenge (should it be developed) is for it to be used as a whitener, in conjunction with fluoride. Even at very low concentrations – like around 20% of the fluoride content found in most commercial toothpastes – the results would achieve good levels of enamel remineralisation and brightening.
Ultimately it could only be of benefit to those with already good oral hygiene. It’s doubtful it would make any difference to someone with a history of not taking great care of their teeth.
In 2015, the team of Professor Janet Moradian-Oldak of the University of Southern California’s Herman Ostrow School of Dentistry fabricated a hydrogel form of synthetic enamel.
To be used in an approach similar to the one proposed by Dr Yamagishi, the science focused on the chemical events that occur externally of the enamel-making cells. It meant utilising the appropriate ions and proteins that create the hydroxyapatite crystals.
What they developed is a technology that is yet to reach the complex hierarchical structure of enamel, but has a functional level that can improve damaged enamel. Current products put a layer of organic material on the tooth and numb nerve endings with potassium nitrate, but the relief is only temporary.
The peptide, however, addresses the problem at the source.
It has proven to work on human teeth, but they were extracted ones, and it’s not clear if the treatment will work inside the human mouth.
According to 2019 publications, although the hydrogel is a complete product it requires full clinical trials, and in the case of human drug safety regulations, that can take up to 10 years.
If the product is safe and passes all the regulatory protocols, it will essentially be a preventive treatment for early carious lesions by preventing the decay’s progression.
The issue with this treatment is a really slow regrowth rate – 2.7µm took 48 hours of treatment, which equals approximately 17,777 hours for one millimeter of enamel: more than 2 years of continuous clinical treatment. Obviously for it to be an appropriate therapy, the technology needs massive improvement.
At this point it doesn’t look like a viable treatment for cavities, but it may be helpful for treating enamel erosion in the future.
And by future, that’s likely 15-20 years before it’s commercially viable.
The Tooth Regeneration Market is an evolving industry, still supply-chain impacted by the pandemic, and the war in Ukraine.
The current major players are Unilever, Straumann, Dentsply Sirona, 3M, Zimmer Biomet, Ocata Therapeutics, Integra LifeSciences, and Datum Dental. Globally, its worth is projected to reach $US2046.2 billion by 2028, from $US1506 billion in 2021.
Money talks; science walks quickly toward it. But not fast enough to regenerate your teeth. So do the hard yards yourself – the old way. Brush properly and regularly, floss, watch your diet and see your dentist.
It’s all well and good to have faith in the future but sometimes that’s all it is – faith. Not certitude.
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