2010 - UCSF School of Dentistry - University of California, San ...

human hair. The fibers, in turn, are
packed into rods, with many rods
projecting from the underlying dentin
to the tooth surface. These rows
align into bundles, which bend into
the shape of the tooth crown. It’s
complicated, sophisticated and
precisely controlled – a remarkable
engineering feat accomplished by
engineers the naked eye cannot see.
Baby teeth left under the pillow
for the tooth fairy might have a pearly
shine, but enamel really is more
similar in its crystalline regularity to
the shells that enclose pearls. Enamel
is composed of the mineral calcium
phosphate, arranged in a crystal
structure known as hydroxyapatite.
Seashells are made from calcium
carbonate. Both teeth and seashells
are more complex than they might
first appear. To Habelitz, these
structures represent the pinnacle of
materials science in nature.
“I was fascinated to learn that
Mother Nature can organize and
control the formation and crystallization
of materials on a level that
we cannot,” he says. “The research
now is mainly aimed at understanding
the principles of protein-guided
growth of crystals.” Habelitz is
singling out various proteins in
enamel for closer study. The main
protein present in enamel as it grows
and mineralizes is called amelogenin.
Already, Habelitz and his lab group
have discovered that amelogenin
makes protein sheets that slowly
elongate and that may guide the
growth of hydroxyapatite crystals.
It’s a Blast!
Habelitz also is looking at the
structure and formation of dentin,
the softer underlying material that
supports the enamel tooth crown.
“Dentin is another really fascinating
tissue,” he enthuses.
The biochemical events that give
rise to dentin are better understood
than those that contribute to enamel
formation. Dentin also consists largely
of hydroxyapatite, but dentin is more
similar to bone in that it contains the
structural protein collagen and other
organic materials. Compared with
enamel, dentin is more amenable to
study in humans because the cells
that give rise to dentin – called
odontoblasts – are long-lived, unlike
ameloblasts, which disappear once
tooth formation is complete.
Still, the more heterogeneous
structure of dentin and the cellular
arrangements that give rise to new
dentin within the tooth pulp are
extraordinarily complex, Habelitz
notes. Many mysteries remain,
despite decades of study.
In an effort to grow dentin in
vitro, Habelitz has partnered with
Tejal Desai, PhD, a bioengineer
with the School of Medicine. They
are not simply mixing the right
chemicals in a test tube. They are
working with living cells, positioning
odontoblasts on a microscopic
scaffolding, or matrix. The goal is to
re-create the structure of newly
formed dentin by mimicking the
natural configuration of odontoblasts
and the structures to which they
give rise within the tooth pulp.
A major focus is on the crucial
interface between odontoblasts and
ameloblasts – the junction where
dentin and enamel normally meet and
become tightly bound to each other.
The ultimate goal is to grow an entire
tooth, de novo.
“I think the engineering mind is
strong in me,” Habelitz says. “I want
to produce or create something. But I
also have a fascination about science,
and how things actually work in
living systems. I really enjoy bringing
the two together – to understand the
science and then to apply it.
“It’s a very collaborative
environment at UCSF, and that’s
very important to me,” he says. “It’s
impossible to do this kind of research
by yourself. You need to develop
many collaborations, and you need
input from different angles – biology,
engineering, chemistry. We have all
of that here.” n
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