Tag Archives: tooth decay

Regenerating dental enamel

For anyone who’s concerned about their dental enamel, this research might prove encouraging. From a June 1, 2018 news item on Nanowerk,

Researchers at Queen Mary University of London [UK][ have developed a new way to grow mineralised materials which could regenerate hard tissues such as dental enamel and bone.

Enamel, located on the outer part of our teeth, is the hardest tissue in the body and enables our teeth to function for a large part of our lifetime despite biting forces, exposure to acidic foods and drinks and extreme temperatures. This remarkable performance results from its highly organised structure.

However, unlike other tissues of the body, enamel cannot regenerate once it is lost, which can lead to pain and tooth loss. These problems affect more than 50 per cent of the world’s population and so finding ways to recreate enamel has long been a major need in dentistry.

A June 1, 2018 Queen Mary University of London press release, which originated the news item, provides more detail,

The study, published in Nature Communications, shows that this new approach can create materials with remarkable precision and order that look and behave like dental enamel.

The materials could be used for a wide variety of dental complications such as the prevention and treatment of tooth decay or tooth sensitivity – also known as dentin hypersensitivity.

Simple and versatile

Dr Sherif Elsharkawy, a dentist and first author of the study from Queen Mary’s School of Engineering and Materials Science, said: “This is exciting because the simplicity and versatility of the mineralisation platform opens up opportunities to treat and regenerate dental tissues. For example, we could develop acid resistant bandages that can infiltrate, mineralise, and shield exposed dentinal tubules of human teeth for the treatment of dentin hypersensitivity.”

The mechanism that has been developed is based on a specific protein material that is able to trigger and guide the growth of apatite nanocrystals at multiple scales – similarly to how these crystals grow when dental enamel develops in our body. This structural organisation is critical for the outstanding physical properties exhibited by natural dental enamel.

Lead author Professor Alvaro Mata, also from Queen Mary’s School of Engineering and Materials Science, said: “A major goal in materials science is to learn from nature to develop useful materials based on the precise control of molecular building-blocks. The key discovery has been the possibility to exploit disordered proteins to control and guide the process of mineralisation at multiple scales. Through this, we have developed a technique to easily grow synthetic materials that emulate such hierarchically organised architecture over large areas and with the capacity to tune their properties.”

Mimic other hard tissues

Enabling control of the mineralisation process opens the possibility to create materials with properties that mimic different hard tissues beyond enamel such as bone and dentin. As such, the work has the potential to be used in a variety of applications in regenerative medicine. In addition, the study also provides insights into the role of protein disorder in human physiology and pathology.

Here’s a link to and a citation for the paper,

Protein disorder–order interplay to guide the growth of hierarchical mineralized structures by Sherif Elsharkawy, Maisoon Al-Jawad, Maria F. Pantano, Esther Tejeda-Montes, Khushbu Mehta, Hasan Jamal, Shweta Agarwal, Kseniya Shuturminska, Alistair Rice, Nadezda V. Tarakina, Rory M. Wilson, Andy J. Bushby, Matilde Alonso, Jose C. Rodriguez-Cabello, Ettore Barbieri, Armando del Río Hernández, Molly M. Stevens, Nicola M. Pugno, Paul Anderson, & Alvaro Mata. Nature Communicationsvolume 9, Article number: 2145 (2018) Published 01 June 2018 DOI: https://doi.org/10.1038/s41467-018-04319-0

This paper is open access.

One final comment, this work is at the ‘in vitro’ stage. More colloquially, this is being done in a petri dish or glass vial or some other container and it’s going to be a long time before there are going to be any human clinical trials, assuming the work gets that far.

Nanoscale elements that govern the behaviour of our teeth

Are we going to be adopting atomically correct dental hygiene practices in the future? It’s certainly a possibility given the latest Australian research announced in a Sept. 7, 2016 news item on Nanowerk (Note: A link has been removed),

With one in two Australian children reported to have tooth decay in their permanent teeth by age 12, researchers from the University of Sydney believe they have identified some nanoscale elements that govern the behaviour of our teeth.

Material and structures engineers worked with dentists and bioengineers to map the exact composition and structure of tooth enamel at the atomic scale.

Using a relatively new microscopy technique called atom probe tomography, their work produced the first-ever three-dimensional maps showing the positions of atoms critical in the decay process.

The new knowledge on atom composition at the nanolevel has the potential to aid oral health hygiene and caries prevention, and has been published today in the journal Science Advances(“Atomic-scale compositional mapping reveals Mg-rich amorphous calcium phosphate in human dental enamel”).

A Sept. 8, 2016 University of Sydney press release, which originated the news item, expands on the theme (Note: A link has been removed),

Professor Julie Cairney, Material and Structures Engineer in the Faculty of Engineering and Information Technologies, said:

“The dental professionals have known that certain trace ions are important in the tough structure of tooth enamel but until now it had been impossible to map the ions in detail.

“The structure of human tooth enamel is extremely intricate and while we have known that magnesium, carbonate and fluoride ions influence enamel properties scientists have never been able to capture its structure at a high enough resolution or definition.”

“What we have found are the magnesium-rich regions between the hydroxyapatite nanorods that make up the enamel.”

“This means we have the first direct evidence of the existence of a proposed amorphous magnesium-rich calcium phosphate phase that plays an essential role in governing the behaviour of teeth. “

Co-lead researcher on the study, Dr Alexandre La Fontaine from the University’s Australian Centre for Microscopy and Microanalysis, said:

“We were also able to see nanoscale ‘clumps’ of organic material, which indicates that proteins and peptides are heterogeneously distributed within the enamel rather than present along all the nanorod interfaces, which was what was previously suggested.

“The mapping has the potential for new treatments designed around protecting against the dissolution of this specific amorphous phase.

“The new understanding of how enamel forms will also help in tooth remineralisation research.”

Here’s a link to and a citation for the paper,

Atomic-scale compositional mapping reveals Mg-rich amorphous calcium phosphate in human dental enamel by Alexandre La Fontaine, Alexander Zavgorodniy, Howgwei Liu, Rongkun Zheng, Michael Swain, and Julie Cairney. Science Advances  07 Sep 2016: Vol. 2, no. 9, e1601145 DOI: 10.1126/sciadv.1601145

This paper is open access.

Nanoparticles for breaking up plaque and preventing cavities

There may be iron in your tooth care future if a team of researchers at the University of Pennsylvania have their way. From a July 26, 2016 news item on ScienceDaily,

The bacteria that live in dental plaque and contribute to tooth decay often resist traditional antimicrobial treatment, as they can “hide” within a sticky biofilm matrix, a glue-like polymer scaffold.

A new strategy conceived by University of Pennsylvania researchers took a more sophisticated approach. Instead of simply applying an antibiotic to the teeth, they took advantage of the pH-sensitive and enzyme-like properties of iron-containing nanoparticles to catalyze the activity of hydrogen peroxide, a commonly used natural antiseptic. The activated hydrogen peroxide produced free radicals that were able to simultaneously degrade the biofilm matrix and kill the bacteria within, significantly reducing plaque and preventing the tooth decay, or cavities, in an animal model.

“Even using a very low concentration of hydrogen peroxide, the process was incredibly effective at disrupting the biofilm,” said Hyun (Michel) Koo, a professor in the Penn School of Dental Medicine’s Department of Orthodontics and divisions of Pediatric Dentistry and Community and Oral Health and the senior author of the study, which was published in the journal Biomaterials. “Adding nanoparticles increased the efficiency of bacterial killing more than 5,000-fold.”

A July 25, 2016 University of Pennsylvania news release, which originated the news item, describes the genesis of the work and provides more details about the current research (Note: A link has been removed),

The work built off a seminal finding by Gao [Lizeng Gao, a postdoctoral researcher in Koo’s lab] and colleagues, published in 2007 in Nature Nanotechnology, showing that nanoparticles, long believed to be biologically and chemically inert, could in fact possess enzyme-like properties. In that study, Gao showed that an iron oxide nanoparticle behaved similarly to a peroxidase, an enzyme found naturally that catalyzes oxidative reactions, often using hydrogen peroxide.

When Gao joined Koo’s lab in 2013, he proposed using these nanoparticles in an oral setting, as the oxidation of hydrogen peroxide produces free radicals that can kill bacteria.

“When he first presented it to me, I was very skeptical,” Koo said, “because these free radicals can also damage healthy tissue. But then he refuted that and told me this is different because the nanoparticles’ activity is dependent on pH.”

Gao had found that the nanoparticles had no catalytic activity at neutral or near-neutral pH of 6.5 or 7, physiological values typically found in blood or in a healthy mouth. But when pH was acidic, closer to 5, they become highly active and can rapidly produce free radicals.

The scenario was ideal for targeting plaque, which can produce an acidic microenvironment when exposed to sugars.

Gao and Koo reached out to Cormode [David Cormode, an assistant professor of radiology and bioengineering], who had experience working with iron oxide nanoparticles in a radiological imaging context, to help them synthesize, characterize and test the effectiveness of the nanoparticles, several forms of which are already FDA-approved for imaging in humans.

Beginning with in vitro studies, which involved growing a biofilm containing the cavity-causing bacteria Streptococcus mutans on a tooth-enamel-like surface and then exposing it to sugar, the researchers confirmed that the nanoparticles adhered to the biofilm, were retained even after treatment stopped and could effectively catalyze hydrogen peroxide in acidic conditions.

They also showed that the nanoparticles’ reaction with a 1 percent or less hydrogen peroxide solution was remarkably effective at killing bacteria, wiping out more than 99.9 percent of the S. mutans in the biofilm within five minutes, an efficacy more than 5,000 times greater than using hydrogen peroxide alone. Even more promising, they demonstrated that the treatment regimen, involving a 30-second topical treatment of the nanoparticles followed by a 30-second treatment with hydrogen peroxide, could break down the biofilm matrix components, essentially removing the protective sticky scaffold.

Moving to an animal model, they applied the nanoparticles and hydrogen peroxide topically to the teeth of rats, which can develop tooth decay when infected with S. mutans just as humans do. Twice-a-day, one-minute treatments for three weeks significantly reduced the onset and severity of carious lesions, the clinical term for tooth decay, compared to the control or treatment with hydrogen peroxide alone. The researchers observed no adverse effects on the gum or oral soft tissues from the treatment.

“It’s very promising,” said Koo. “The efficacy and toxicity need to be validated in clinical studies, but I think the potential is there.”

Among the attractive features of the platform is the fact that the components are relatively inexpensive.

“If you look at the amount you would need for a dose, you’re looking at something like 5 milligrams,” Cormode said. “It’s a tiny amount of material, and the nanoparticles are fairly easily synthesize, so we’re talking about a cost of cents per dose.”

In addition, the platform uses a concentration of hydrogen peroxide, 1 percent, which is lower than many currently available tooth-whitening systems that use 3 to 10 percent concentrations, minimizing the chance of negative side effects.

Looking ahead, Gao, Koo, Cormode and colleagues hope to continue refining and improving upon the effectiveness of the nanoparticle platform to fight biofilms.

“We’re studying the role of nanoparticle coatings, composition, size and so forth so we can engineer the particles for even better performance,” Cormode said.

The funding agencies provide a note of interest (Note: Links have been removed),

The study was funded by the International Association for Dental Research/GlaxoSmithKline Innovation in Oral Health Award, National Science Foundation and University of Pennsylvania Research Foundation.

Presumably the industry as represented by the GlaxoSmithKline Innovation in Oral Health Award is keeping a close eye on this work.

Here’s a link to and a citation for the paper,

Nanocatalysts promote Streptococcus mutans biofilm matrix degradation and enhance bacterial killing to suppress dental caries in vivo by Lizeng Gao, Yuan Liu, Dongyeop Kim, Yong Li, Geelsu Hwang, Pratap C. Naha, David P. Cormode, & Hyun Koo. Biomaterials Volume 101, September 2016, Pages 272–284 doi:10.1016/j.biomaterials.2016.05.051

This paper is behind a paywall.

Repairing sensitive teeth with silica nanoparticles

Don’t rush out to talk to your dentist yet but researchers at the University of Birmingham (UK) have devised a promising technique for repairing sensitive teeth according to a Sept. 16, 2015 news item on ScienceDaily,

Researchers at the University of Birmingham have shown how the development of coated silica nanoparticles could be used in restorative treatment of sensitive teeth and preventing the onset of tooth decay.

The study, published in the Journal of Dentistry, shows how sub-micron silica particles can be prepared to deliver important compounds into damaged teeth through tubules in the dentine.

The tiny particles can be bound to compounds ranging from calcium tooth building materials to antimicrobials that prevent infection.

A Sept. 16, 2015 university of Birmingham press release (also on EurekAlert), which originated the news item, expands on the research,

Professor Damien Walmsley, from the School of Dentistry at the University of Birmingham, explained, “The dentine of our teeth have numerous microscopic holes, which are the entrances to tubules that run through to the nerve. When your outer enamel is breached, the exposure of these tubules is really noticeable. If you drink something cold, you can feel the sensitivity in your teeth because these tubules run directly through to the nerve and the soft tissue of the tooth.”

“Our plan was to use target those same tubules with a multifunctional agent that can help repair and restore the tooth, while protecting it against further infection that could penetrate the pulp and cause irreversible damage.”

The aim of restorative agents is to increase the mineral content of both the enamel and dentine, with the particles acting like seeds for further growth that would close the tubules.

Previous attempts have used compounds of calcium fluoride, combinations of carbonate-hydroxypatite nanocrystals and bioactive glass, but all have seen limited success as they are liable to aggregate on delivery to the tubules. This prevents them from being able to enter the opening which is only 1 to 4 microns in width.

However, the Birmingham team turned to sub-micron silica particles that had been prepared with a surface coating to reduce the chance of aggregation.

When observed using high definition SEM (Scanning Electron Microsopy), the researchers saw promising signs that suggested that the aggregation obstacle had been overcome.

Professor Zoe Pikramenou, from the School of Chemistry at the University of Birmingham, said, “These silica particles are available in a range of sizes, from nanometre to sub-micron, without altering their porous nature. It is this that makes them an ideal container for calcium based compounds to restore the teeth, and antibacterial compounds to protect them. All we needed to do was find the right way of coating them to get them to their target.  We have found that different coatings does change the way that they interact with the tooth surface.”

“We tested a number of different options to see which would allow for the highest level particle penetration into the tubules, and identified a hydrophobic surface coating that provides real hope for the development of an effective agent.”

Our next steps are to optimise the coatings and then see how effective the particles are blocking the communication with the inside of the tooth.  The ultimate aim is to provide relief from the pain of sensitivity.

Here’s a citation and a link to the paper,

The deposition and imaging of silica sub-micron particles in dentine by Sunil Claire, Anthony Damien Walmsley, Sophie Glinton, Hayley Floyd, Rachel Sammons, Zoe Pikramenou. Journal of Dentistry October 2015 Volume 43, Issue 10, Pages 1242–1248 DOI: http://dx.doi.org/10.1016/j.jdent.2015.08.002
Published Online: August 07, 2015

This paper is behind a paywall.