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Dentistry Infectious Diseases / Bacteria / Viruses Penn team uses nanoparticles to break up plaque and prevent cavities

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Penn team uses nanoparticles to break up plaque and prevent cavities

MNT Knowledge Center
Adapted Media Release
Published: Thursday 28 July 2016

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 journalBiomaterials. "Adding nanoparticles increased the efficiency of bacterial killing more than 5,000-fold."

The paper's lead author was Lizeng Gao, a postdoctoral researcher in Koo's lab. Coauthors were Yuan Liu, Dongyeop Kim, Yong Li and Geelsu Hwang, all of Koo's lab, as well as David Cormode, an assistant professor of radiology and bioengineering with appointments in Penn's Perelman School of Medicine and School of Engineering and Applied Science, and Pratap C. Naha, a postdoctoral fellow in Cormode's lab.

The work built off a seminal finding by Gao 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, 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


CA Clear Aligner Clinical Protocol, and Why It is as It is

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Biological bases of CA® CLEAR-ALIGNER Protocol

CA® CLEAR-ALIGNER protocol is based on sequential aligners carried out over the impressions, and plaster casts carried out each 4 weeks. One “step” of treatment includes a plaster cast set-up, 3 aligners (CA®-soft, CA®-medium, CA®-hard) pressure moulded over this plaster cast set-up, and a report on movements carried out in the set-up. It corresponds to one month of treatment.

The treatment starts when the diagnosis is finished. The impressions are taken, and a 0.5 mm dental movement is carried out in the plaster cast set-up. Over this plaster cast, 3 CA® CLEAR-ALIGNERS of 3 different thicknesses are pressure moulded (Figs. 1 and 2).

    – CA®-soft, a 0.5 mm aligner.
    – CA®-medium, a 0.625 mm aligner.
    – CA®-hard, a 0.75 mm aligner.

The Evolution of Dentistry: What is trending now and what will the future hold?

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Major trends in dental technology?

The progress in dental technology has been revolutionary as well as evolutionary. We have acquired and adapted relevant equipment from various segments of the medical field as well as developing new methodologies from within. If we wish to predict the technological direction of dentistry, it is a simple matter to examine proven medical gadgetry, and to imagine its focused application to the oral cavity. Typically, medical innovation proceeds its dental counterpart by almost 20 years.

Dental radiology had changed very little since the times of Roentgen. The introduction of digital radiography reduced patient radiation exposure, added the ability to manipulate diagnostic images, and simplified data storage. In less than 25 years, digital radiology has redefined dental diagnostics. As we move confidently and more affordably towards mainstream tomography, the dentist will begin to view both health and disease very differently. The next decade will see the arrival of the three dimensional diagnostic standard: the practitioner will have the opportunity to specifically locate disease and examine the generalized health status utilizing 3-D modeling. Rather than a three-dimensional superimposition on a two-dimensional film or screen, requiring an educated guess to pinpoint the exact position of the problem, tomography will enable the most conservative and direct treatment possible.

The rise of oral cancer in groups not previously considered to be at risk (younger non-smokers, non-drinkers, and females) is rather alarming. A rapid visual scan of the oral cavity during routine examination may disclose suspicious tissue changes that have progressed to, or have begun at, the surface. Unfortunately, many pre-cancerous epithelial lesions occur below the tissue surface at the basal membrane. These subsurface oral abnormalities are invisible to the naked eye until they grow through the epithelial layer, at which stage the best opportunities for early discovery and intervention have been lost. The recent combination of high-power LED lights and innovative filtration utilizes natural fluorescence visualization to identify clinically invisible anomalies. Cancers and precancerous epithelial lesions down to the basal membrane are now identified and mapped for follow-up investigation (biopsy) and treatment. The technique is noninvasive and not unpleasant. As such, it is well accepted by patients, and sets the standard for diagnostic techniques of the future.

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