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Penn team uses nanoparticles to break up plaque and prevent cavities

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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.

"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 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.


Pediatrics / Children's Health Dentistry Nutrition / Diet Obesity / Weight Loss / Fitness Children consuming sports drinks unnecessarily

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A high proportion of 12-14 year olds are regularly consuming sports drinks socially, increasing their risk of obesity and tooth erosion, concludes a Cardiff University School of Dentistry survey.

Published in the British Dental Journal, the survey looked at 160 children in four schools across South Wales and concluded that children are attracted to sports drinks because of their sweet taste, low price, and availability, with most parents and children not aware that sports drinks are not intended for consumption by children.

Half of the children surveyed claimed to drink sports drinks socially and most (80%) purchased them in local shops. The majority (90%) also claimed that taste was a factor and only 18% claimed to drink them because of the perceived performance enhancing effect. Price was one of the top three recorded reasons for purchase and, of particular concern, 26% of children also cited leisure centres as purchase sources.

Maria Morgan, senior lecturer in dental public health at Cardiff University, said: "The purpose of sports drinks are being misunderstood and this study clearly shows evidence of high school age children being attracted to these high sugar and low pH level drinks, leading to an increased risk of dental cavities, enamel erosion and obesity.

"Dental health professionals should be aware of the popularity of sports drinks with children when giving health education or advice or designing health promotion initiatives."

The Faculty of Sport and Exercise Medicine (FSEM) is calling for tighter regulation around the price, availability and marketing of sports drinks to children, especially surrounding the school area, to safeguard general and dental health.

Dr Paul D Jackson, President of the FSEM UK, said: "The proportion of children in this study who consume highcarbohydrate drinks, which are designed for sport, in a recreational non-sporting context is of concern.

"Sports drinks are intended for athletes taking part in endurance and intense sporting events, they are also connected with tooth decay in athletes and should be used following the advice of dental and healthcare teams dedicated to looking after athletes. Water or milk is sufficient enough to hydrate active children, high sugar sports drinks are unnecessary for children and most adults."

Russ Ladwa, chair of the British Dental Association's Health and Science Committee, added: "The rise of sports drinks as just another soft drink option among children is a real cause for concern, and both parents and government must take note. They are laden with acids and sugars, and could be behind the decay problems we're now seeing among top footballers.

"Sports drinks are rarely a healthy choice, and marketing them to the general population, and young people in particular, is grossly irresponsible. Elite athletes might have reason to use them, but for almost everyone else they represent a real risk to both their oral and their general health."


Nine Shades of Full-Mouth Whitening in twenty Minutes

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In my private practice in the greater Detroit area, I have offered in-office whitening for my patients for many years. Patients feel great about themselves when they see the results, and it’s also a consistent source of additional revenue for the practice.

But many practices still do not provide in-office whitening for various reasons. Some doctors think that in-office whitening takes too long, and thus wastes valuable chair time. Others may be afraid that they’ll cause patient sensitivity or they don’t think that they can sell the service to patients.

A new laser whitening system (ezlase Whitening and Pain Relief System [BIOLASE Technology]) solves all of that. In the last year, I have used the ezlase laser (BIOLASE Technology) with their special whitening handpiece and proprietary LaserWhite20 gel to provide excellent results for more than 200 patients. Since each case took less than 20 minutes of procedure time (plus patient prep and post-op), it’s easy to schedule several whitening cases per day.

Lasers Versus Simple Light

First, it’s very important to understand that not all in-office whitening systems actually utilize a laser. Although many systems utilize light, they do not use laser light. Laser energy is absorbed by special particles in the whitening gel to activate the hydrogen peroxide, which accelerates the whitening process faster than “simple” light does, so the procedure time is dramatically shorter. In a typical day, I can schedule almost twice as many in-office whitening cases with a laser compared to other whitening systems.

The US Food and Drug Administration first gave clearance for an in-office laser whitening system almost 10 years ago. Today’s products not only perform faster, but they are also very easy to learn and integrate into your practice. In addition, the same dental laser used for whitening can also be used for everyday soft-tissue and hygiene procedures, such as gingivectomies, troughing for crown and bridge impressions, and sulcular debridement. It can even be used to temporarily relieve minor pain, such as pain caused by temporomandibular joint disorder. On the other hand, other light-based whitening systems can’t offer anything more. The multiprocedure capabilities of lasers help your practice realize an even greater return on investment.

Easy Technique

The protocol for the ezlase whitening system is very easy, and no special training is required. The first step is to prep the patient. After a thorough examination, remove plaque and superficial stains, and then measure and record the initial shade of the patient’s teeth. Apply petroleum jelly to the lips, insert cheek retractors, then apply and cure liquid dam (included in BIOLASE’s whitening gel kit) onto the gingiva.

The next step is to mix the whitening base gel and activator gel together. The base and activator gels are shipped in separate syringes, so connect the syringes together, and then push each plunger back and forth for about 30 to 45 seconds. The resulting mixture is a gel with 38% hydrogen peroxide concentration. The mixed gel does not have a long shelf life, so you should only mix right before applying it to a patient’s teeth.

Connect a brushed applicator tip to the syringe of mixed gel, and apply a thin, uniform layer to teeth 4 to 13 and 20 to 29. Make sure that the gel does not contact the patient’s gingival, tongue, or lip, and that it is not swallowed.

Before activating the laser, ensure that everyone in the operatory wears the appropriate laser safety glasses(included with the ezlase laser). Place a disposable clear protective cap over the laser handpiece, and connect the handpiece to the laser delivery system. Set the ezlase laser to 7 W power, continuous wave mode, and 200 Joules energy output (all explained in the included, easy to follow instructions for use).

The handpiece is designed to treat a full quadrant of 4 to 5 teeth at a time. So place the handpiece about 1 mm away from a quadrant, and then activate the laser for 30 seconds to allow 200 J of laser energy to be applied. Continue this step for the remaining quadrants, and then repeat the process for all quadrants one more time. Dividing the teeth into quadrants allows the laser to accelerate the whitening process while minimizing heat induced to the teeth. Leave the gel on the teeth for an additional 5 minutes to allow the teeth to absorb the laser-activated hydrogen peroxide, allowing continued whitening after the laser exposures.

Remove the gel with high-speed suction, and then flush with an air and water spray to remove any residual gel. Apply a second coat of mixed gel using a new brushed applicator tip, and repeat the laser process described above.

That’s it! Less than 20 minutes of gel to tooth contact time and laser application.

To finish up, thoroughly rinse with water, and carefully remove the liquid dam. Apply moist cotton gauze over the gums and teeth and wait for a few minutes to rehydrate enamel and tissue. If desired, a final polish can be performed with a fine grade paste to give luster and shine to the teeth.

Finally, measure the new shades, compare it to the original, and discuss the outcomes with your patient.

Great Results

The results are immediate. Patients who’ve never had in-office whitening before can’t believe how good their new smile looks before even getting out of the dental chair. At this point, it is critical to advise them not to consume products that stain teeth for up to the next 48 hours, such as coffee, red wine, tobacco, tea, some fruits, tomato sauce, etc. If followed, the results will continue to get even better during this time.

An ADA Professional Product Review from Spring 2008 (Vol. 3, Issue 2) and a study published in the Journal of Cosmetic Dentistry in Summer 2003 (Volume 19, Number 2), both concluded that laser whitening systems provided approximately 9 shades of improvement, compared to approximately 8 shades of improvement on non-laser systems (using the VITA Shade Guide Brightness Scale).(1)

In my practice, I can typically achieve six shades of improvement, and sometimes the improvement is as good as nine shades.

But even with so many great outcomes, it is very important to discuss potential results with patients before the procedure begins. The degree of whitening varies from patient to patient based on type of stain, enamel thickness, tooth structure, and age. So patients deserve to have realistic expectations before the treatment begins.

Reduced Sensitivity

A concern that some doctors have had with in-office whitening is patient sensitivity. But with laser whitening, my patients have experienced little to no sensitivity.

Because of the unique properties of the laser, the gel-to-tooth contact time is about half as long as other in-office whitening systems that use a similar concentration of hydrogen peroxide gel. Less contact time results in less sensitivity.

When the laser shines on the teeth, patients experience a warm sensation, but it is not painful or discomforting. The laser shines on the teeth for only short, 30-second intervals, compared to other light-based in-office whitening systems that shine a heat-producing lamp for several minutes at a time.

The BIOLASE whitening gel kit also includes a syringe of desensitizing gel with potassium nitrate that can be applied after the procedure to further minimize sensitivity. Also, as a precautionary measure, doctors may recommend appropriate pain relief medication 30 to 60 minutes prior to the procedure and also post-operatively.


Your patients will love how quickly they can whiten their smile with little to no discomfort, and referrals will increase. You won’t have a problem scheduling more whitening cases either because of the easy and short procedure. And by also utilizing your laser for soft-tissue and hygiene procedures, and for temporary relief of minor pain, it will turn out to be one of the best investments you’ve made for your practice.

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