Why Is This Idea No Longer Science Fiction?

Oral health is, for financial reasons, the first source of care foregone in France. Even if the 100% health reform deployed from 2019 made it possible to democratize crowns in the event of tooth loss, as soon as we start to cause major surgery, it’s another story. Implants, which nevertheless constitute the most lasting solution, are not covered by the fully reimbursed basket of care. Thus, to replace a lost tooth, the patient must take out his wallet and pay thousands of euros. A perfectly accepted two-tier care policy and an accounting logic disconnected from the needs of the French populationeven more so in the current inflationary climate.

Maybe one day we will see the end of this economic impasse thanks to the latest cutting-edge innovations in the fieldwhich revolve around three axes: genetic deactivation in Japan, organ culture in the United States and biomineralization in China.

The Japanese hack: waking up the third set of teeth via RNA

When we are children, our deciduous teeth grow in, then replaced by our permanent teeth, which we theoretically keep until the end of our lives. But we all have, buried in our gums, the germs necessary for a third set of teethlike certain animals. It was discovered by a Japanese team, led by Professor Katsu Takahashi, from Osaka University; a discovery shared in December 2024, in an article published in the journal Journal of Oral Biosciences.

In this case, when we lose a tooth, why can’t another one replace it? Because the bud (tooth forming under the gum before it grows) is blocked by the action of a protein, called USAG-1, which acts as a powerful growth inhibitor. Simply put, USAG-1 attaches to bone morphogenesis proteins to render them inactive, like a dead weight attached to a runner’s ankle.

To prevent this inhibition, these Japanese researchers developed a monoclonal antibody that targets and neutralizes this protein. The growth process thus unlocked, the genes responsible for the formation of dentin (mineralized tissue of the tooth) and enamel (white outer layer of the tooth) can activate again.

Human clinical trials, which began at the end of 2024 after convincing tests on mice and ferrets, aim to commercialize this treatment from 2030. « The idea that humans only have two sets of teeth is a simple misconception. We keep within ourselves a genetic “emergency kit”, we just need to know how to reactivate it “, explains Dr. Takahashi.

Organoids and liquid enamel: bioengineering applied to dental care

Other teams elsewhere in the world are also working on this problem, notably researchers from the University of Washington, who have successfully created dental organoids in the laboratory. These are miniature living teeth, grown from stem cells, which can synthesize enamel on their own.

Instead of simply plugging a hole with an inert material, these multicellular structures mimic embryonic development: they stimulate ameloblasts, specialized cells responsible for secreting proteins that harden to form enamel. Ultimately, the idea is toimplant these organoids in the cavities so that they repair the tooth from the inside by producing new, perfectly integrated organic matter.

China is also involved, thanks to the work of a team from Zhejiang University, which published this article in 2019 in the journal Science Advances. They managed to develop a gel based on calcium phosphate which stimulates the natural process of biomineralization. It is through this process that cells form enamel and dentin, forming strong structures from calcium and phosphate ions. Applied to a damaged area, it helps to restorecreate a layer of enamel 3 micrometers thick.

« The structure and robustness of the enamel we synthesized are strictly indistinguishable from natural tissue. Our ambition is to offer a biological alternative to current fillings, which use materials that are completely foreign to our body. If the schedule is respected, the first human tests could begin within one to two years “, explains Dr Zhaoming Liu, co-author of the study.

It appears quite obvious that these three treatments are still in the embryonic stage and that their democratization will not happen in a snap of the fingers. Make no mistake: the first regenerative therapies will be billed at full Price, reserved for specific patients. capable of bearing stratospheric research and development costs. Not to mention that they will have to cross the European and French regulatory labyrinthmore tortuous than in Asia or the USA. Before hoping for a Marketing Authorization (AMM), these innovations will have to validate Phase III trials on cohorts of thousands of patients to guarantee that tooth regrowth is not accompanied by any side effects. We can therefore expect, quite realistically, that none of these three innovations will not be available from us before the middle of the next decade.