Thanks to This Israeli Breakthrough, Orthodontia Could Be a Matter of Mere Months

People have been using knives to cut tissue for 4,000 years, says Assaf Zinger of the Technion - and thought of replacing the scalpel in gum surgery with enzymes.

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Surgery is scary, even if it's elective and cosmetic. Only weirdos like to think about a knife slicing into their flesh. What if you could replace the surgeon's scalpel with a cream that does the work without pain and in a fraction of the time? 

Assaf Zinger, a doctoral student at the Technion - Israel Institute of Technology, Department of Chemical-Engineering, is working on developing that very thing.

"People have been using knives to cut tissue for 4,000 years," Zinger told Haaretz. "I mean to replace that with enzymes."

Enzymes are proteins with an activity. They are your body's machines - builders and destroyers. For instance, they are responsible for breaking down the food you eat in your stomach and intestinal tract.

For starters, Zinger is developing his concept to replace a specific operation, developed in the United States, which can shorten the time teenagers need to wear braces on their teeth from two years to about six months. It is, as is the way of all surgery, a bit gruesome, involving cutting into the gums to the root of the teeth and severing the collagen fibers holding the teeth in place.

Pre-orthodontia panoramic X-ray (Dreamstime.com)
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But what, says Zinger, if the same effect could be achieved painlessly and less harmfully by applying a cream containing nanoparticles that in turn contain collagenase, a naturally-occurring enzyme that degrades collagen?

At the end of the day, orthodontic patients could even wind up paying less money for the pleasure of straight teeth, he adds.

Guided missile in your mouth

The nanoparticulate cream with the enzyme is applied directly to the intact gums, in the tiny space between the teeth. The enzyme, called collagenase, weakens the collagen, enabling the teeth to move more freely and with less pain under the pressure of the braces, shortening the correction process.

"The collagenase is like a guided missile: it doesn't break down the elastase that holds the whole region together," Zinger told the Technion Magazine.

And so he started. "We took nature's scalpel, which is proteins that occur naturally in our bodies," he says.

Phrased a tad less romantically, Zinger began his work with studying the effect of collagenase on collagen isolated from rat tails. Using electron microscopy, he observed that massive collagen fibers do degrade into smaller fibers, as expected.

Then, helped by a team of engineers and physicians and his mentor Prof. Avi Schroeder, he built the animal model. Phrased a tad less scientifically, the team designed and built braces for rats.

Worry not: the braces were installed with the rats under anesthetic. Zinger admits that during the first four days after installation, the subject rodents lost weight, which worried him.

"I consulted with an orthodontist. When you put a 16-year old in braces he also loses weight for days because he has to learn to eat with them. It’s the same with rats," he says, adding that right after that adjustment period, the rats regained their original weight.

Once confident the orthodontic device was not causing them distress (no weight loss, no signs of behavioral changes over time), Zinger applied the collagenase, enclosed in nanoparticulate "fat bubbles" (liposomes) , that could release the enzyme in a controlled fashion over time.

As said the cream is applied between the teeth, the area one cleans with toothpicks –and observed the result, with the help of electron microscopy and advanced biological assays.

And indeed it worked beautifully, in the rats, who presumably now have gorgeous smiles.

What about over-reaction? Could these collagenase enzymes, albeit locked into fatty nanoparticles, dissolve the mouth? "No," says Zinger firmly, and explains: Enzymes only work in a very strict body region and range of acidity. To stop the reaction between the enzymes and our collagen all we need to do is wash the mouth out with orange juice, for instance.

The project was awarded funding by the Chief Scientist at the Economy Ministry and the scientists are looking for financing – possibly venture financing - to take the concept to the next stage, to bring the product to the market.

As for cost, Zinger points out that these days, collagenase can be industrially produced at cosmeceutical grade. There is also the advantage of sparing the potential infection from surgery; economizing on orthodontist fees; and an enormous potential saving in pain.

One of the lesser dwelled-upon aspects of braces is that inadequate oral hygiene, which is rather the norm, can lead to a great deal of damage, including receding gums. One may have straight teeth but the world sees rather too much of them. The longer one wears braces, the more likely this is to happen.

In the future, he hopes his enzymatic surgery concept can be expanded from externalities such as bum gums and twisted teeth to internal conditions such as Dupuytren's contracture - a crippling thickening of the tendons in the hand. Then, after flashing that gorgeous smile, patients can wave without pain as well.