MATERIALS SCIENCE
Cool Jobs: Drilling into the secrets of teeth
Scientists focus on teeth to make better fillings, grow new chompers and explore ancient diets
Researchers are moving well beyond the pick and drill to treat dental problems and “read” the history of our ancient ancestors' health from their not-sopearly whites.
DRAGONIMAGES/ISTOCKPHOTO
By Esther Landhuis
February 1, 2018 at 6:45 am
Several years ago, Dean Ho bit into a sandwich and chipped a tooth. His dentist
patched it up, but several months later the tooth started throbbing. “It was the worst
pain I’d ever felt in my life,” Ho recalls.
The inside of the tooth’s root had become infected. Now it needed a root canal
treatment. Many patients dread this procedure. It’s where a dentist drills into the
tooth and then scrapes out the infected tissue. Afterward, this new hole is filled with
a rubber-like material. More than he feared this process, Ho was intrigued by it.
He didn’t understand exactly what a root canal was. That might come as a surprise,
since he works at the School of Dentistry at the University of California, Los Angeles.
But Ho doesn’t treat patients. He is a bioengineer. Indeed, he heads a lab that uses
science and engineering principles to solve problems in biology and medicine.
Reclining in the dental chair, tools and tubes sticking out of his mouth, Ho typed on
his smartphone. This curious researcher wanted to “chat” as his dentist set to work.
What are you doing? Is it going to hurt? How much longer? When the root-canal
treatment was done, Ho had more questions — the kind a bioengineer might ask.
Curious about the tooth-filling material, he asked: “Look, is there anything cool about
it? Could anything be made better?”
Those timely musings were key. They spurred the creation of a new material that
could improve root-canal treatments for generations to come. Ho isn’t the only
scientist who has sunk his teeth into … well, teeth! A similar “what if” moment
inspired a Boston biologist to try growing new teeth in the lab. And for one
archaeologist, bad teeth have turned out to be a boon. They are chock full of DNA —
genetic material that offers clues to the diets and diseases of ancient cultures.
A better tooth filling
As Ho learned, infections can be a big and painful problem for root-canal patients.
Even after the dentist fills an infected tooth, the seal won’t be perfect. Often it will
have little holes. These can allow bacteria to creep in.
Nanodiamonds are tiny, organized carbon
structures. Here’s what a nanodiamond looks
like at the atomic level. Because their many
surfaces can bind to a wide range of
molecules, these nanoparticles are used in
drug therapies — and now in novel dental
fillers.
AMERICAN CHEMICAL SOCIETY/DEAN HO GROUP
Pondering this problem, Ho had an idea. “The wheels were turning while [my dentist]
was working on me,” he notes. For years, Ho’s lab had worked with diamonds — not
the kind in jewelry, but super-small ones known as nanodiamonds. They’re made
from groups of carbon atoms. Each group can be less than a thousandth the width of
a human hair. In 2007, his team showed that these teeny pieces of carbon have an
unusual blend of flexibility and strength. That suits them for big jobs, such as
carrying cell-killing drugs to cancer cells. Since then, Ho’s team has found more uses
for nanodiamonds. The material can create sharper medical images and help bone
regrow.
At his dentist’s office, Ho had another idea. How about using nanodiamonds to make
a better root-canal filler?
Like ordinary diamonds, nanodiamonds are very hard. They can strengthen materials
to which they are added. They also are great at latching onto chemicals, including
bacteria-killing drugs. These medicines, called antibiotics, can shut down infections.
Adding drug-carrying nanodiamonds to the existing filler material could make rootcanal treatments more reliable. At the same time, Ho thought, they might keep teeth
from getting re-infected.
Back in the lab, he and his coworkers got to work designing this new filler. They
compared it to the usual material. For this work, they used teeth that dentists had
already extracted from people’s mouths. To fill an infected tooth, dentists need
something that’s squishy while it’s being applied, but tough once it hardens. The
nanodiamond material looked promising. And lab tests proved it stronger than
conventional fillers.
Best yet, this new material indeed can fight infections.
Researchers have created an improved
dental filler studded with nanodiamonds (size
shown relative to tweezers). When they add
microbe-killing drugs, the material prevents
bacteria from growing. So far they’ve tested
the material on teeth that had already been
extracted and in those of three people
needing root canals.
AMERICAN CHEMICAL SOCIETY/DONG-KEUN LEE
When the researchers spread bacteria onto the two different surfaces, far more
bacteria died on the new filler than on the conventional one.
“If the bugs make contact [with the filler], the drug will get them,” Ho says. His team
first described this filling material a little more than two years ago in the journal ACS
Nano. So far they’ve tried the new filler in three people who needed root canals.
When checked six months later, the new material was holding up well and the
patients had no further tooth decay. The researchers reported these data in the Nov.
7, 2017 Proceedings of the National Academy of Sciences. Now they’re gearing up for a
larger study with 30 people.
Ho also wants his research to motivate “future explorers of the world” — like his
preschooler children. “Wouldn’t it be cool if the kids could actually know what I’m
doing? There’s impact that can be made beyond the technical side,” he says. Toward
that end, Ho has been working with an artist to create a comic book. It not only
explains what nanodiamonds are but also how they’re used. (Take a peek at the
comics, which you can find at the bottom of this webpage:
http://www.projectndx.com/new-page/.)
Lab-grown teeth
Sometimes, teeth rot so much that they cannot be fixed by a root-canal treatment.
Instead, dentists have to replace them with dentures or tooth implants. In general,
however, such “fake” teeth are far from ideal. “People don’t like them,” notes Pamela
Yelick. She’s a biologist at Tufts University School of Dental Medicine in Boston. The
reason: Dentures don’t “feel” the same as real teeth do. They also don’t adapt as well
to the effects of chewing. Finally, many people find them inconvenient to clean and
uncomfortable to wear.
Dental implants have the opposite problem, Yelick adds. Normally teeth attach to
soft tissue, called ligaments, which help absorb the forces of chewing. But dentures
and implants have no such cushion. That can make fake teeth painful or cause them
to break.
Yelick wondered if her team could do a better job. She wanted to find a way to help
people grow new teeth.
The idea popped into her head during a lecture by a scientist from the
Massachusetts Institute of Technology, in Cambridge. The MIT scientist spoke about
his team’s work to engineer artificial livers for kids awaiting a liver transplant.
Explainer: What is a stem
cell?
To grow new livers, the MIT group was using stem cells. Those are rare cells within the
human body. Instead of dividing into just one type of cell — such as a skin cell,
neuron or bone cell — they can produce any of many different types of cells. Hearing
about that research, “I was blown away,” Yelick recalls. “I was like: ‘This is so cool!
Could you do this with teeth?’”
To pursue this idea, her team first needed the right stem cells — ones that can give
rise to all of the different cell types that make up a tooth. For that, they needed a
cheap source of teeth for study. Yelick got creative. She found a pig slaughterhouse
that was willing to provide jaws from butchered animals.
Back at the lab, Yelick’s team chiseled out the buds of would-be molars.
Scientists can grow teeth in the lab. Here’s
one grown from stem cells isolated from pigs’
tooth buds. Dental pulp cells, clustered in the
center, are surrounded by pink dentin (pink
stain) and enamel (dark brown stain), the
hard material that forms the outside of a
tooth.
WEIBO ZHANG AND PAMELA C. YELICK
Using existing methods for sorting rare stem cells out of immune-cell mixtures, the
researchers isolated stem cells from the pig’s teeth. (Stem cells are identified by a
signature collection of proteins on their surface.) The researchers placed the stem
cells into dishes filled with a liquid made from cell nutrients. The dishes also
contained a three-dimensional mesh known as a scaffold. In several months, those
cells grew and organized into “beautiful little tooth crowns,” Yelick says. That was
quite a feat. It made the front page of the Boston Globe in 2002.
Since then, Yelick’s team has made tooth crowns starting with dental stem cells from
people. They often use wisdom teeth or other teeth extracted by an orthodontist. One
day the researchers hope to use this method as an alternative to root canals.
They aren’t there yet. But here’s how they think it could work. Instead of filling
damaged teeth with some rubber-like material, they’d apply a gel that contains
dental stem cells. Those cells would develop into the various cell types that make up
the tooth’s connective tissue. Essentially, Yelick says, this would let stem cells grow on
site to replace rotten tissue that had been cleared out during a root canal.
Before anything is done in people, the team needs to do more work in pigs. The pig
experiments cost hundreds of thousands of dollars. And these studies would need to
be repeated many times to get reliable data. However, Yelick predicts, it should be
possible to regenerate human teeth from stem cells within the next 10 years.
Archaeological goldmine
While Ho and Yelick work to save or replace bad teeth, Christina Warinner relishes
the rotting chompers. And, she adds, the dirtier, the better!
Graduate student Nisha Patel (left) and
Christina Warinner place samples taken from
ancient teeth into a centrifuge. It can
separate ancient DNA from other parts of
cells. They wear protective clothing to avoid
contaminating their samples with modern
DNA from their hair, skin and clothing.
CHRISTINA WARINNER
Warinner works at the University of Oklahoma in Norman. But until 2020, she’ll be a
visiting scientist at the Max Planck Institute for the Science of Human History in Jena,
Germany. As a molecular anthropologist, she analyzes DNA in ancient bones. Her
goal: to learn more about the lives of ancient peoples. Surprisingly, “teeth are one of
the best-preserved parts of the skeleton,” she says.
And the most valuable part of ancient teeth? Plaque. “All that stuff getting stuck in
your teeth?” It turns rock hard, Warinner says. And that allows it to survive the
ravages of time. Materials from saliva cover the tooth with a tough buildup of
minerals. As a result, a tooth “doesn’t decompose in the same way as the rest of your
body.”
For Warinner, that hardened stuff that dentists scrape off of our teeth holds a
remarkable wealth of information. That’s because dental plaque contains loads of
DNA from trapped food particles, bacteria in the mouth — even a person’s own cells.
By analyzing those bits of genetic information, she and others can learn about what
ancient people ate and which diseases they suffered.
The true ‘Paleo’ diet
For example, Warinner’s team discovered that the same microbes that cause gum
disease today also troubled ancient peoples. And on the food side, her research has
shown that the term “Paleo diet” is misleading. People who follow this modern diet
avoid dairy and grains. They eat only fruits, vegetables and other foods that they
believe humans consumed during the Paleolithic Era, some 10,000 to 2.6 million years
ago.
Books and posters often depict the Paleo diet as one full of bright, healthy foods. “I
don’t disagree that eating a breakfast of eggs, avocados and blueberries sounds
wonderful,” says Warinner. Alas, her data show, these foods are “brighter, fleshier,
sweeter and more calorie-dense than anything a person back then would have had
access to.”
By studying ancient teeth like these, from a
middle-aged man in medieval Germany
around A.D. 1100, anthropologists can
discover what people ate and what diseases
they had long, long ago.
CHRISTINA WARINNER
Wild avocados of old, for example, had almost no edible fruit — at least not
compared to the plump Haas avocados that grocery stores sell today. As for carrots
and broccoli, Warinner says, those weren’t even “invented” until the 16th and 17th
centuries, after years of plant breeding. Veggies eaten by ancient people were
woody, fibrous and tough. Today we would consider these weeds or ornamental
plants, says Warinner. Indeed, she adds, “Many people today would not recognize
common Paleolithic foods as foods at all.”
As a child, Warinner recalls, someone gave her a book of stamps with Egyptian
hieroglyphs (HY-roh-glifs). The ancient world it described enthralled her. A little while
later, she got interested in science. The young student had no idea that it was
possible to blend elements of history and biology. But that’s what she’s now able to
do.
“I loved learning about the natural world, understanding how things work and why
they work,” she says. In college, Warinner discovered archaeology. She loved the way
that this field could merge with other sciences. “I could look at questions that relate
to the human past.” And she could do it, she says, “using tools and techniques
coming out of biology and chemistry, which I loved so much.”
Warinner’s studies have taken her all over the globe. She has excavated in the hot,
wet Central American jungles of Belize (Beh-LEEZ) and in a beautiful, cold,
mountainous region of Mexico.
More recently, Warinner went to Nepal, high in the Himalayas. She traveled with a
team of high-altitude archaeologists. They studied ancient people who colonized
some of the world’s harshest, high-altitude environments. These sites have few
sources of food or other resources.
When a debate arose over which population arrived first, the team settled the issue
by reconstructing human genes and more from DNA fragments in excavated bones.
Now they’re trying to identify genetic features that helped those ancient people
adapt to such cold areas, such intense sun and so little oxygen.
Warinner’s advice to students: “Stay curious and keep your minds open. I never
dreamed I could be doing something so much fun!”
CITATIONS
Journal:​D.K. Lee et al. Clinical validation of a nanodiamond-embedded thermoplastic
biomaterial. Proceedings of the National Academy of Sciences. Vol 114, November 7, 2017, p. E9445.
doi: 10.1073/pnas.1711924114.
Journal:​W. Zhang et al. Decellularized tooth bud scaffolds for tooth regeneration. Journal of
Dental Research. Vol. 96, May 1, 2017, p. 516. doi: 10.1177/0022034516689082.
Journal:​E.E. Smith and P.C. Yelick. Progress in bioengineered whole tooth research: from bench
to dental patient chair. Current Oral Health Reports. Vol. 3, December 2016, p. 302. doi:
10.1007/s40496-016-0110-2.
Journal:​C. Jeong et al. Long-term genetic stability and a high-altitude East Asian origin for the
peoples of the high valleys of the Himalayan arc. Proceedings of the National Academy of Sciences.
Vol. 113, July 5, 2016, p. 7485. doi: 10.1073/pnas.1520844113.
Journal:​D.K. Lee et al. Nanodiamond—gutta percha composite biomaterials for root canal
therapy. ACS Nano. Vol. 9, November 24, 2015, p. 11490. doi: 10.1021/acsnano.5b05718.
Journal: H. Huang et al. Active nanodiamond hydrogels for chemotherapeutic delivery. Nano
Letters. Vol. 7, November 2007, p. 3305. doi: 10.1021/nl071521o.
Journal:​C.S. Young et al. Tissue engineering of complex tooth structures on biodegradable
polymer scaffolds. Journal of Dental Research. Vol. 81, October 1, 2002, p. 695. doi:
10.1177/154405910208101008.
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