Tooth Regeneration May Replace Drill-and-Fill

Dentistry has taken the same approach to tooth decay — filling cavities — for decades, but new techniques for rebuilding teeth from the inside out could transform the profession over the next decade.
Photo: Hollingsworth/Corbis

The next time your children get cavities, they might get tooth regeneration instead of fillings.

That's because materials scientists are beginning to find just the right solutions of chemicals to rebuild decayed teeth, rather than merely patching their holes. Enamel and dentin, the materials that make teeth the strongest pieces of the body, would replace the gold or ceramic fillings that currently return teeth to working order.

"What we're hoping to have happen is to catch [decaying teeth] early and remineralize them," said Sally Marshall, a professor at the University of California at San Francisco. Marshall gave a talk last week at the spring meeting of the Materials Research Society on rebuilding the inner portions of teeth.

While regrowing your uncle's toothless grin from scratch is still a decade away, the ability to use some of the body's own building materials for oral repair would be a boon to dentists, who have been fixing cavities with metal fillings since the 1840s. Enamel and dentin are remarkably strong and long-lasting, and they can repair themselves. But as scientists are continuing to find out, dentin in particular is a remarkably complex structure.

The outer covering of teeth is enamel. The body makes it by growing tiny mineral crystals in a highly regular crystal lattice. Underneath that ceramic-like covering, dentin is like hard clay reinforced by fibers of collagen, similar to the way adobe bricks contain clay reinforced by straw fibers.

"The tooth is a beautiful structure," said Van Thompson, dentistry professor and chairman of New York University's Department of Biomaterials and Biomimetics.

But teeth, because they are made from minerals, are susceptible to what is essentially erosion. Acids, like those produced by bacteria or Coca-Cola, demineralize the enamel of the teeth. Usually the body is constantly repairing small amounts of damage, Marshall said. But when the body's defenses become overwhelmed, bacteria break through into the dentin below, and you get tooth decay, commonly called a cavity.

The acid produced by the bacteria eats into the minerals in the dentin, turning it mushy and useless. Normal dentin is twice as stiff as pinewood, but damaged dentin is more like rubber, which makes it pretty hard to chew with.

Marshall's newest work, which has been accepted for publication in the Journal of Structural Biology, focuses on regrowing dentin in damaged teeth with the help of a calcium-containing solution of ions (electrically charged particles).

By putting a layer of the solution on individual test teeth, Marshall has already been able to remineralize some parts of the teeth. The challenge is to get the crystals to regrow throughout the dentin.

To heal properly, the crystals need to form from the bottom of the tooth up to the enamel. Marshall isn't sure whether that's happening yet, but she is confident that she'll find a way to restore dentin functionality over the next few years.

Stephen Bayne, professor of dentistry at the University of Michigan, noted that while many groups are working on regrowing teeth, Marshall has "incredible stature" in dentistry for her groundbreaking work helping dentists understand the structure of the tooth.

Still, even with the recent progress, the very complexity that Marshall and other researchers have discovered in the humble tooth is likely to keep her technique out of your local dentist's office for a few more years.

"We're still a ways from being able to grow back dentin and enamel," Bayne said.

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Scientists Discover 356 Animal Inclusions Trapped In Opaque Amber 100 Million Years Old

Paleontologists from the University of Rennes (France) and the ESRF have found the presence of 356 animal inclusions in completely opaque amber from mid-Cretaceous sites of Charentes (France). The team used the X-rays of the European light source to image two kilogrammes of the fossil tree resin with a technique that allows rapid survey of large amounts of opaque amber. This is the only known method to discover inclusions in detail in fully opaque amber.

Examples of virtual 3D extraction of organisms embedded in opaque amber: a) Gastropod Ellobiidae; b) Myriapod Polyxenidae; c) Arachnid; d) Conifer branch (Glenrosa); e) Isopod crustacean Ligia; f) Insect hymenopteran Falciformicidae. (Credit: M. Lak, P. Tafforeau, D. Néraudeau (ESRF Grenoble and UMR CNRS 6118 Rennes))

Opaque amber has always been a challenge for paleontologists. Researchers cannot study it because the naked eye cannot visualize the presence of any fossil inclusion inside. In the Cretaceous sites like those in Charentes, there is up to 80% of opaque amber. It is like trying to find, in complete blindness, something that may or may not be there.

However, the paleontologists Malvina Lak, her colleagues from the University of Rennes and the ESRF paleontologist Paul Tafforeau, together with the National Museum of Natural History of Paris, have applied to opaque amber a synchrotron X-ray imaging technique known as propagation phase contrast microradiography. It sheds light on the interior of this dark amber, which resembles a stone to the human eye. “Researchers have tried to study this kind of amber for many years with little or no success. This is the first time that we can actually discover and study the fossils it contains”, says Paul Tafforeau.

The scientists imaged 640 pieces of amber from the Charentes region in southwestern France. They discovered 356 fossil animals, going from wasps and flies, to ants or even spiders and acarians. The team was able to identify the family of 53% of the inclusions.

Most of the organisms discovered are tiny. For example, one of the discovered acarians measures 0.8 mm and a fossil wasp is only 4 mm. “The small size of the organisms is probably due to the fact that bigger animals would be able to escape from the resin before getting stuck, whereas little ones would be captured more easily”, explains Malvina Lak.

Water to see tiny fossils better

The surface features of amber pieces, like cracks, stand out more in the images than the fossil organisms in the interior when using synchrotron radiation. In order to solve this problem, scientists soaked the amber pieces in water before the experiment. Because water and amber have very similar densities, immersion made the outlines of the amber pieces and the cracks almost invisible. At the same time, it increased overall inclusion visibility, leading to better detection and characterization of the fossils.

Classification of species

Once discovered on the radiographs, some of the organisms were imaged in three dimensions and virtually extracted from the resin. The high quality of these 3D reconstructions enables paleontologists to precisely study and describe the organisms. The success of this experiment shows the high value of the ESRF for the study of fossils. “Opaque amber hosts many aspects of past life on our planet that are still unknown, and the use of third generation synchrotron sources will continue to play an important role in unveiling them”, asserts Malvina Lak.

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Blind to Change, Even as It Stares Us in the Face

GOOD EYE In deciding what to focus on, we scan and sweep until something sticks out and brings our bouncing cones to a halt, as shown above.

Leave it to a vision researcher to make you feel like Mr. Magoo.

When Jeremy Wolfe of Harvard Medical School, speaking last week at a symposium devoted to the crossover theme of Art and Neuroscience, wanted to illustrate how the brain sees the world and how often it fumbles the job, he naturally turned to a great work of art. He flashed a slide of Ellsworth Kelly’s “Study for Colors for a Large Wall” on the screen, and the audience couldn’t help but perk to attention. The checkerboard painting of 64 black, white and colored squares was so whimsically subtle, so poised and propulsive. We drank it in greedily, we scanned every part of it, we loved it, we owned it, and, whoops, time for a test.

Dr. Wolfe flashed another slide of the image, this time with one of the squares highlighted. Was the highlighted square the same color as the original, he asked the audience, or had he altered it? Um, different. No, wait, the same, definitely the same. That square could not now be nor ever have been anything but swimming-pool blue ... could it? The slides flashed by. How about this mustard square here, or that denim one there, or this pink, or that black? We in the audience were at sea and flailed for a strategy. By the end of the series only one thing was clear: We had gazed on Ellsworth Kelly’s masterpiece, but we hadn’t really seen it at all.

The phenomenon that Dr. Wolfe’s Pop Art quiz exemplified is known as change blindness: the frequent inability of our visual system to detect alterations to something staring us straight in the face. The changes needn’t be as modest as a switching of paint chips. At the same meeting, held at the Italian Academy for Advanced Studies in America at Columbia University, the audience failed to notice entire stories disappearing from buildings, or the fact that one poor chicken in a field of dancing cartoon hens had suddenly exploded. In an interview, Dr. Wolfe also recalled a series of experiments in which pedestrians giving directions to a Cornell researcher posing as a lost tourist didn’t notice when, midway through the exchange, the sham tourist was replaced by another person altogether.

Beyond its entertainment value, symposium participants made clear, change blindness is a salient piece in the larger puzzle of visual attentiveness. What is the difference between seeing a scene casually and automatically, as in, you’re at the window and you glance outside at the same old streetscape and nothing registers, versus the focused seeing you’d do if you glanced outside and noticed a sign in the window of your favorite restaurant, and oh no, it’s going out of business because, let’s face it, you always have that Typhoid Mary effect on things. In both cases the same sensory information, the same photonic stream from the external world, is falling on the retinal tissue of your eyes, but the information is processed very differently from one eyeful to the next. What is that difference? At what stage in the complex circuitry of sight do attentiveness and awareness arise, and what happens to other objects in the visual field once a particular object has been designated worthy of a further despairing stare?

Visual attentiveness is born of limited resources. “The basic problem is that far more information lands on your eyes than you can possibly analyze and still end up with a reasonable sized brain,” Dr. Wolfe said. Hence, the brain has evolved mechanisms for combating data overload, allowing large rivers of data to pass along optical and cortical corridors almost entirely unassimilated, and peeling off selected data for a close, careful view. In deciding what to focus on, the brain essentially shines a spotlight from place to place, a rapid, sweeping search that takes in maybe 30 or 40 objects per second, the survey accompanied by a multitude of body movements of which we are barely aware: the darting of the eyes, the constant tiny twists of the torso and neck. We scan and sweep and perfunctorily police, until something sticks out and brings our bouncing cones to a halt.

The mechanisms that succeed in seizing our sightline fall into two basic classes: bottom up and top down. Bottom-up attentiveness originates with the stimulus, with something in our visual field that is the optical equivalent of a shout: a wildly waving hand, a bright red object against a green field. Bottom-up stimuli seem to head straight for the brainstem and are almost impossible to ignore, said Nancy Kanwisher, a vision researcher at M.I.T., and thus they are popular in Internet ads.

Top-down attentiveness, by comparison, is a volitional act, the decision by the viewer that an item, even in the absence of flapping parts or strobe lights, is nonetheless a sight to behold. When you are looking for a specific object — say, your black suitcase on a moving baggage carousel occupied largely by black suitcases — you apply a top-down approach, the bouncing searchlights configured to specific parameters, like a smallish, scuffed black suitcase with one broken wheel. Volitional attentiveness is much trickier to study than is a simple response to a stimulus, yet scientists have made progress through improved brain-scanning technology and the ability to measure the firing patterns of specific neurons or the synchronized firing of clusters of brain cells.

Recent studies with both macaques and humans indicate that attentiveness crackles through the brain along vast, multifocal, transcortical loops, leaping to life in regions at the back of the brain, in the primary visual cortex that engages with the world, proceeding forward into frontal lobes where higher cognitive analysis occurs, and then doubling back to the primary visual centers. En route, the initial signal is amplified, italicized and annotated, and so persuasively that the boosted signal seems to emanate from the object itself. The enhancer effect explains why, if you’ve ever looked at a crowd photo and had somebody point out the face of, say, a young Franklin Roosevelt or George Clooney in the throng, the celebrity’s image will leap out at you thereafter as though lighted from behind.

Whether lured into attentiveness by a bottom-up or top-down mechanism, scientists said, the results of change blindness studies and other experiments strongly suggest that the visual system can focus on only one or very few objects at a time, and that anything lying outside a given moment’s cone of interest gets short shrift. The brain, it seems, is a master at filling gaps and making do, of compiling a cohesive portrait of reality based on a flickering view.

“Our spotlight of attention is grabbing objects at such a fast rate that introspectively it feels like you’re recognizing many things at once,” Dr. Wolfe said. “But the reality is that you are only accurately representing the state of one or a few objects at any given moment.” As for the rest of our visual experience, he said, it has been aptly called “a grand illusion.” Sit back, relax and enjoy the movie called You.

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