Are 'living fillings' the future of teeth restoration? Enamel-growing organoids could open up regenerative dentistry

It’s one of life’s hard truths: Once tooth enamel is gone, you can’t get it back. And while tooth tech has come a long way since the days of wooden dentures, there’s no regrowing lost teeth.

But that may not be the case forever. In a new study published Aug. 14 in Development Cell, a research team led by scientists from the University of Washington School of Dentistry described how it used human stem cells to grow organoids, or 3D tissue cultures, that produce working enamel-producing ameloblasts

“This is a critical first step to our long-term goal to develop stem cell-based treatments to repair damaged teeth and regenerate those that are lost,” co-author, researcher and dentist Hai Zhang, Ph.D., said in a press release

To create the organoids, the researchers studied and then replicated the genetic program that leads fetal stem cells to grow into specialized enamel-producing cells. This involved a gene sequencing technique called single-cell combinatorial indexing RNA sequencing—sci-RNA-seq, for short—which shows which genes are active at different stages of cell development. 

After using sci-RNA-seq to see which genes were active in different developmental phases, the researchers used a program called Monocle to map the gene expression patterns that drive stem cells to differentiate into ameloblasts. This gave them a “blueprint” to help build ameloblasts.

The researchers then exposed the stem cells to chemicals that would promote gene expression in the same sequence identified by sci-RNA-seq. After some “trial and error,” as the researchers put it in the press release, they successfully coaxed the stem cells to become ameloblasts. In the course of doing so, they discovered a previously uncharacterized cell type: a subodontoblast, believed to be a precursor for another type of cell, an odontoblast, that’s necessary for tooth formation.  

Together, the different cell types could be induced to form organoids that resembled structures found in developing human teeth. These organoids secreted ameloblastin, amelogenin and enamelin, three proteins that form the basis of enamel. Under the right conditions, including a process called remineralization, these proteins could form into enamel. 

While dentist Arun Narang, who runs a private dental practice in Mississauga, Ontario, called the findings “intriguing,” as they could one day help many patients, he noted that there are plenty of questions around practical application.

“I’m still waiting to find out how the proteins from the organoids are placed on the teeth or how they will help those with declining enamel regrow it,” Narang said in an email to Fierce Biotech Research. “That is something we would need to wait and see about.” 

The scientists are working on ways to refine the process so the enamel becomes as durable as teeth. Once that’s accomplished, they could move to growing it in a laboratory and eventually use it to fill cavities—or, perhaps, “living fillings” that grow on their own, the researchers described in the press release. 

“This may finally be ‘the Century of Living Fillings’ and human regenerative dentistry in general,” researcher and project lead Hannele Ruohola-Baker, Ph.D., said in the release.