Nature favors the fittest, and tooth enamel is one of evolution’s success stories.
Dinosaurs and ancient sharks sported enamel on their big choppers eons ago, as have newly evolved creatures ever since. Treated right, enamel lasts a lifetime.
“Enamel is the best crown material there is,” asserts German-born Stefan Habelitz, PhD, engineer and materials scientist in the UCSF School of Dentistry.
Habelitz ought to know. He worked on high-tech bio-ceramics for bone implants and tooth restorations for a decade before coming to UCSF in 1999 to blaze a new research trail. Now he’s investigating enamel at the dental school’s Marshall Lab, where researchers fruitfully focus on every facet of teeth knowing they’re nothing to take for granted.
When enamel breaks down due to tooth decay or trauma, dentists do an admirable job patching things up with gold crowns and ceramic caps or composites. But no man-made material can compare to enamel, Habelitz says. Enamel is designed to crack at the sites of specific microstructures within it, and normally over time it does. But enamel rarely cracks all the way through or fails, as ceramics often do. And better than gold or composites, enamel remains integrally attached to the underlying dentin upon which it first forms.
With the aid of state-of-art electron scanning, atomic force and optical microscopes, Habelitz at last is glimpsing the hidden secrets of enamel.
This crowning achievement is the work of a type of living cell called an ameloblast. Ameloblasts makes a variety of specialized proteins that guide different steps in enamel production. Enamel buzzes with cellular and biochemical activity as it is being made, but within the finished product, cells, proteins and other signs of life have all but vanished. Enamel is the most mineralized substance in the body.
Habelitz lectures on mineralized tissues, ceramics and composites to first-year dental students, as well as to postdoctoral fellows and to postgraduates training in prosthodontics, orthodontics and pediatric dentistry. The postgraduates joke with Habelitz about whether he soon will be growing replacement enamel in test tubes and driving them out of business.
That’s not on the horizon in the near term, Habelitz concedes. Yet he aims to catch up with nature’s autopilot engineers, to steal a page from their blueprints and to match them with his own inventions.
“If we can understand how proteins make enamels, we hope to be able to design our own proteins to make engineered structures,” he says. It may indeed be possible to grow enamel in vitro, or to grow new ceramic structures, very precisely, at the smallest possible scale. “Well-defined nanostructures,” Habelitz calls them. Beyond dentistry, such materials could serve as longer lasting and better wearing surface coatings in a wide range of applications, including bone implants, bullet-proof materials and micro-circuits, for example.
With the Marshall Lab’s microscopes, Habelitz can see how enamel, like a ceramic, is constructed from crystals. The crystals grow into fibers. Each fiber is about 50 nanometers across – one thousand times finer than a 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.
UCSF School of Dentistry scientist Stefan Habelitz studies tooth enamel, and aims to build a tooth de novo. This micrograph image shows the human tooth-enamel protein amelogenin as it self-assembles in the lab, forming a network of ribbons about 30 nanometers in diameter and 20 to 30 nanometers long. In the tooth, the ribbons support the growth of hydroxyapatite crystals, the main mineral component of enamel.
Baby teeth left under the pillow for the tooth fairy might have a pearl-like shine, but shiny enamel really is more similar in its crystalline regularity to the shells that enclose pearls. Enamel is comprised of the mineral calcium phosphate, arranged in a crystal structure known as hydroxyapatite. Sea shells are made from calcium carbonate. (So are pearls, for that matter) Both teeth and sea shells 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,” says Habelitz, who is singling out various proteins in enamel for closer study. “The research now is mainly aimed at understanding the principals of protein-guided growth of crystals.”
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.
Mysteries of Dentin
Habelitz also is looking at the structure and formation of dentin, the softer underlying material which 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 to 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 bio-engineer with the UCSF 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.
Their goal is to recreate 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 at the junction where dentin and enamel normally meet and become tightly bound to one another. An 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. 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.”
Editor’s note: This story was originally published in the 2010 UCSF Dentistry Magazine.
UCSF School of Dentistry, Research