ANN ARBOR – Scientists in Japan have begun the world’s first human clinical trials of an experimental drug designed not just to repair missing teeth — but to actually grow new ones using the body’s own biological systems. This development, years in the making, could fundamentally change how dentistry treats tooth loss and congenital dental disorders.

Why Humans Can’t Naturally Regrow Teeth

Unlike many animals, humans are what scientists call diphyodonts — we develop two sets of teeth in our lifetimes: baby (deciduous) teeth, and adult (permanent) teeth. Once the permanent set emerges, the biological pathways that produce new tooth growth shut down, meaning lost teeth are gone forever without intervention.

This is very different from polyphyodont animals like sharks, which continuously grow replacement teeth throughout life — a trait researchers often reference in regenerative studies.

At a biological level, tooth development is a complex developmental process involving a series of interactions between epithelial and mesenchymal cells. During early embryogenesis, tooth buds form first, then proceed through stages known as the bud, cap, and bell stages, ultimately giving rise to enamel,

dentin, and root structures. Several signaling pathways — including bone morphogenetic proteins (BMPs) and Wnt signaling — tightly regulate this process. Nature

Once this program completes in childhood, the “switch” that enables tooth generation is turned off, leaving adults unable to regrow teeth naturally.

How the New Drug Works: Unlocking Dormant Growth Potential

The Japanese trial focuses on a protein called Uterine Sensitization Associated Gene-1 (USAG-1), which acts as a brake on tooth growth. In animal studies, blocking USAG-1 helped activate dormant tooth buds and stimulate the growth of additional teeth beyond the normal adult set.

The experimental drug, currently being tested at institutions including Kyoto University and Kitano Hospital in Osaka, uses an antibody-based approach to neutralize USAG-1. By inhibiting this protein’s inhibition of BMP signaling pathways, the drug essentially releases the biological constraints that normally prevent new tooth formation after adulthood.

What the Human Trials Involve

Human trials began in late 2024 and involve roughly 30 adult male participants between the ages of 30 and 64 who are missing at least one tooth. Over the course of about 11 months, participants receive intravenous doses of the drug to assess safety and biological effects. Importantly, preclinical animal studies in ferrets, mice, and dogs showed tooth growth with no major side effects.

If this Phase I safety trial is successful, researchers plan to move on to younger patients — particularly children aged 2 to 7 with congenital absence of several teeth — because they still retain more embryonic-like dental progenitor cells.

Why This Matters

Every year, millions of people worldwide lose teeth due to decay, injury, or aging. Current solutions — dentures, bridges, and dental implants — provide functional replacements but come with limitations: they don’t fully mimic natural tooth biology, they can degrade or fail, and they often require maintenance or replacement.

A therapy that triggers the growth of natural teeth would be a paradigm shift in dental medicine, transforming dentistry from mechanical replacement toward true biological regeneration. Parola Analytics

If further trials confirm safety and effectiveness, researchers and industry watchers believe such a treatment could be commercially available by around 2030 — offering hope to patients born with missing teeth as well as those who lose them later in life.

Where Tooth Regrowth Research Stands Globally

While the Japanese trial is the first in humans, multiple lines of research are advancing the science of dental regeneration:

  • Stem cell approaches: Researchers in the US and Europe are exploring how dental pulp or induced pluripotent stem cells might be guided to form complete new teeth or dental tissues in the lab before implantation.

  • Bioengineered scaffolds: Tissue engineering frameworks could one day support in-mouth tooth growth in ways similar to natural embryonic development.

  • Enamel regeneration: Separate work on gels that can regenerate tooth enamel suggests future technologies may help teeth heal themselves from decay without fillings or crowns.

Taken together, these breakthroughs paint a picture of a future where tooth loss may become not a permanent condition but a biologically correctable one.