A Peptide Based on Amelogenin can Induce Regrowth of Lost Tooth Enamel

Teeth are subject to many problems, most of which are caused by bacteria. Unfortunately, the state of medical technology when it comes to control of harmful bacteria in the mouth lags far behind the policing of bacterial populations in other scenarios and locations. It is fairly well understood how bacteria cause gum disease and cavities, meaning which species are responsible and which mechanisms are important, but so far no lasting strategy for removing unwanted oral bacteria or blocking their activities has made it out of the laboratory and into the clinic. Getting rid of bacteria in the mouth is easy, but ensuring that only certain specific types are removed, and keeping them removed past a few hours or days, has turned out to be far more challenging.

Nonetheless, some promising avenues have emerged, even though they remain somewhere in the process of development. This is the case for methods of regrowth of tooth enamel; I recall discussing a few specific approaches more than a decade ago, and yet here we are, still reliant upon drills and fillings. Some groups have pursued cell and tissue engineering approaches to growing enamel. Back in 2010, a group demonstrated regeneration of cavities in mice by delivering a peptide known to encourage bone formation, and that worked on enamel as well. That attempt was conceptually similar to far more recent research noted here, in which a different peptide is used to spur enamel deposition.

Peptide-based biogenic dental product may cure cavities

Researchers have designed a product that uses proteins to rebuild tooth enamel and treat dental cavities. This can - in theory - rebuild teeth and cure cavities without today's costly and uncomfortable treatments. "Remineralization guided by peptides is a healthy alternative to current dental health care. Peptide-enabled formulations will be simple and would be implemented in over-the-counter or clinical products."

Bacteria metabolize sugar and other fermentable carbohydrates in oral environments and acid, as a by-product, will demineralize the dental enamel. Although tooth decay is relatively harmless in its earliest stages, once the cavity progresses through the tooth's enamel, serious health concerns arise. Good oral hygiene remains the best prevention. Taking inspiration from the body's own natural tooth-forming proteins, researchers came up with a way to repair the tooth enamel. They accomplished this by capturing the essence of amelogenin - a protein crucial to forming the hard crown enamel - to design amelogenin-derived peptides that biomineralize and are the key active ingredient in the new technology.

"These peptides are proven to bind onto tooth surfaces and recruit calcium and phosphate ions." The peptide-enabled technology allows the deposition of 10 to 50 micrometers of new enamel on the teeth after each use. Once fully developed, the technology can be used in toothpaste, gels, solutions and composites as a safe alternative to existing dental procedures and treatments. The technology would enable people to rebuild and strengthen tooth enamel on a daily basis as part of a preventive dental care routine.

Biomimetic Tooth Repair: Amelogenin-Derived Peptide Enables in Vitro Remineralization of Human Enamel

White spot lesions (WSL) and incipient caries on enamel surfaces are the earliest clinical outcomes for demineralization and caries. If left untreated, the caries can progress and may cause complex restorative procedures or even tooth extraction which destroys soft and hard tissue architecture as a consequence of connective tissue and bone loss. Current clinical practices are insufficient in treating dental caries.

A long-standing practical challenge associated with demineralization related to dental diseases is incorporating a functional mineral microlayer which is fully integrated into the molecular structure of the tooth in repairing damaged enamel. This study demonstrates that small peptide domains derived from native protein amelogenin can be utilized to construct a mineral layer on damaged human enamel in vitro. Six groups were prepared to carry out remineralization on artificially created lesions on enamel: (1) no treatment, (2) Ca2+ and PO43- only, (3) 1100 ppm fluoride (F), (4) 20 000 ppm F, (5) 1100 ppm F and peptide, and (6) peptide alone. While the 1100 ppm F sample (indicative of common F content of toothpaste for homecare) did not deliver F to the thinly deposited mineral layer, high F test sample (indicative of clinical varnish treatment) formed mainly CaF2 nanoparticles on the surface.

Fluoride, however, was deposited in the presence of the peptide, which also formed a thin mineral layer which was partially crystallized as fluorapatite. Among the test groups, only the peptide-alone sample resulted in remineralization of fairly thick (10 μm) dense mineralized layer containing HAp mineral, resembling the structure of the healthy enamel. The newly formed mineralized layer exhibited integration with the underlying enamel as evident by cross-sectional imaging. The peptide-guided remineralization approach sets the foundation for future development of biomimetic products and treatments for dental health care.

Comments

There is a company that has had plans to genetically modify the fastest growing strain of bacteria responsible for tooth decay to excrete a benign waste product instead of acid. It would crowd out the decay-causing strain and one treatment would have made you good for life. But like many other great ideas it sits in the valley of funding death.

https://www.oragenics.com/technology-pipeline/lbp/smart

Posted by: Corbin at April 13th, 2018 5:44 PM

I am skeptical about over the counter use. You cannot put it in tooth paste for everyday use otherwise you risk your teeth growing enamel in all possible places, not only the demilitarized spot. And you still have to see a dentist or other kind of specialist. And for the simple cavities the treatment is already simple. The most expensive part is the labor. Then you have the anesthetics and the filling.
With the new treatment you will still need to freeze the nerves and drill the tooth to remove the infected part. then you have to seal it with a temporary filing which promotes the dentin and enamel repair. And you will, probably, need many visits. Provided the regrown enamel is better integrated in the existing tooth and doesn't cause unusual mechanical stresses it might superior to the existing fillings. But that part has to be proven. If might very well grow a fragile part that will chip off or crack the remaining of the tooth.

Anyway, as a kid fear of cavities forced me to reduce my sugar intake.

Posted by: cuberat at April 13th, 2018 6:04 PM

The problem is, even if this produces new enamel in vivo, how to maintain the shape of the tooth? If applied, say, in tooth paste, will enamel not grow all over the surface of the tooth?

Posted by: Antonio at April 13th, 2018 6:06 PM

@Antonio - a problem with current filings is that they are not durable. Usually after 10 years bacteria will get between the filing and the remaining tooth enamel and the filing will have to be re drilled to a deeper level, eventually resulting in the loss of the tooth if the decay reaches the root.

With this tech, the peptide could be applied in a matrix or hydrogel under a filing, increasing the remaining enamel over time, perhaps being reapplied until the point where a filing is no longer necessary.

Posted by: Jim at April 14th, 2018 3:47 AM

This might be useful for generalized cosmetic aging. Teeth enamel wears down over time -- lengthening teeth gives a younger appearance to the face. And hopefully the new enamel would be white, which would cover up old discoloration.

Posted by: Jon at April 14th, 2018 6:57 AM

@John
>And hopefully the new enamel would be white, which would cover up old discoloration

If it produces high quality enamel this treatment can be preceded by bleaching, which is available even OTC. And probably can be tweaked to seal the micro pores to preserve the colour

Posted by: Cuberat at April 14th, 2018 1:17 PM

There's no reason that it couldn't be included in toothpaste; it doesn't have to be at such a high concentration that it causes malformed growths to be useful. Even very low concentrations that only serve to slow the loss of enamel would be helpful.

Posted by: Dennis Towne at April 15th, 2018 11:06 AM

@Dennis Towne
Three are already calcium deposits in the form of tartar. It would be ironic if tartar turned into enamel while leaving unrepaired cavities.
Anyway it is a very promising treatment. It might not be a game changer for the longevity but would be of the first approved nano-microbiology treatment to reach massive adoption scale

Posted by: Cuberat at April 15th, 2018 12:14 PM

I have been tracking a number of agents that bring about new enamelization of tooth damage. Some are already approved drugs - though would have to be used off label.

I think this approach will be fought by dentist and the ADA tooth (no-pun attended) and nail. For several decades the US dentistry industry has essentially focused almost exclusively on building business models and practices that create a more constant income stream from patients. A farming of them if you will.

There have been wide spread criticisms of US dentist (frequently by US dentist themselves) for overly aggressive excavation of decay in teeth - unnecessary removal of healthy material and or premature removal of soft spots for income rather than the patients best interest. Additionally, US dentistry has been criticized for the lack R&D into better and less non-invasive technologies for to preserve and maintain healthy teeth and or the actual repression of it. The possibility of a more natural repair process also has implications on current dental practices - especially the wide spread use of root canals which essentially kills the tooth and would likely make these future natural rebuilding therapies impossible afterwards. Current practices and dentist economics suggest that it will be very difficult to establish healthier dental practices that might involve less billable life long visits by patients.

Posted by: Durwood M. Dugger at April 16th, 2018 1:16 PM

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