Glowing dye lets us peek inside growing bones and teeth

For the first time, biologists have precisely tracked the development of hard biological structures.
Fluorescent dye shows the growth of teeth and bones.
A new tool tracks hard tissue growth like teeth and bones in many species. Gonzalez Lopez et al. Sci. Adv. 2023

Your body contains the stuff of rocks: the calcium-based minerals in bones and teeth. In a process called biomineralization, you produce these materials that harden and stiffen as they grow. So do the bodies of other bony, toothed animals. It’s in shells, too: Iridescent mother-of-pearl forms via biomineralization.

But, historically, biologists struggled to observe how this process worked. Now, scientists have been able to observe it in vivid 3D. Bones and tEEth Spatio-Temporal growth monitoring (BEE-ST), as its creators have named their technique, involves adding dye to nascent bones or budding teeth, then watching the color spread as their host components grow.

BEE-ST’s creators published their work in the journal Science Advances today. If its authors are correct, then this work could be a boon for people who aren’t just studying how bones and teeth grow, but people who want to control that growth themselves.

“Currently, there are no available tools for precise monitoring and measuring the pace of tooth growth in space and time,” says Jan Křivánek, a developmental biologist at Masaryk University in Brno, Czechia, and one of the paper’s authors. BEE-ST, they hope, may change that.

[Related: This new synthetic tooth enamel is even harder than the real thing]

A few methods can accomplish parts of that goal. Today, scientists and medics can rely on a technique called micro-computed tomography, in which they scan an object with X-rays from multiple angles, then stitch the scans together into a 3D image. While this does give observers a 3D perspective, it also only gives a snapshot—moments in time, rather than a coherent sequence of development.

Another potential option is dye. Bone-watchers have known for decades that dye and substances like it can bind with the calcium in these organs. But this is far from a perfect option to watch how calcium-based structures grow. For one, to see into a bone, you typically have to remove the calcium from your sample, which removes the dye. You can get around this by taking a slice of the tooth or bone, but that only gives you a 2D shadow of the larger 3D picture.

Křivánek and his colleagues wanted to see how mouse teeth grew, but they also wanted a more sophisticated way of seeing calcium. So, they decided to adapt the dye method. Fortunately, in the last several years, researchers had developed techniques to see into a tooth without removing the calcium. They could insert dye into a growing tooth or bone and take 3D images of it over time. Every few days, the researchers added batches of new dye to lab mice. The result, when the scientists later placed the teeth under a microscope, was a sequence of stripes: each one marking a different injection.

[Related: We finally know why we grow wisdom teeth as adults]

In the process, they realized that their technique could be used for more than just mouse teeth. They next showed it could work in a mouse’s bones. Then they expanded from mice to representatives of other provinces in the animal kingdom, administering dye to a menagerie of vertebrates: chameleons (reptiles), junglefowl (birds), frogs (amphibians), and zebrafish (fish).

All of this took Křivánek and colleagues several years, but in the end, they think they have created a reliable process for watching how teeth and bones grow. But that doesn’t mean it only serves this purpose. “We strongly believe it will be further tuned for other applications,” Křivánek says.

One of them is a field called tissue engineering, the science and craft of manipulating the tissues of the human body. A “tissue” can be anything from skin to muscle to internal organs—to stronger materials like the hard, tough matter found in bone and tissue. With tools such as stem cells, scientists can strengthen tissue, improve it, or even try to replicate it from scratch. This technology can help heal cracked bones or regenerate missing teeth.

But, in order to engineer anything, would-be bonesmiths first need to understand how their materials behave as they grow. That, Křivánek thinks, is where something like their method could enter the picture. “We basically opened doors,” he says. “Let’s see how the scientific community will use it.”