Is Tooth Regeneration Fishy? Pigs Don’t Fly, But They Have Human-Like Teeth

Adult tooth loss is a worldwide oral health issue, due to congenital or acquired disease, or accident. It’s a common health condition in almost all age groups, and most particularly older demographics. It results in loss of confidence, nutritional decline, gradual social isolation and general quality of life diminishment.

A fully developed human is expected to have 32 teeth. However, genetics has about 1% of the population presenting with fewer, or more. This is part of scientists’ focus in the exploration of the causes and clues to human tooth regeneration, that has been heavily researched for more than two decades.

Currently, treatment for tooth loss is confined to full or partial dentures, autogenus transplantation and dental implants.

The integration of health and life science fundamentals, with advanced chemistry and engineering over the last ten years has advanced tooth regeneration methods and technology. The development of scaffold-based tissue regeneration, and cell and tissue engineering along with animal model gene editing is moving human tooth regeneration out of the realm of possibility into corporeal reality.

Activating the third dentition after the two we already have, is proving a scientifically viable approach to regrowing your own teeth.

No matter how good the colour, shape and material quality of a dental prosthetic, it will always feel foreign because there is no nerve activity and no sensation of temperature.

Not such a bad thing for those with tooth sensitivity, but all in all, while these missing tooth solutions are effective, nothing, but nothing beats the possibility of replacing your own with your own.

Scientists at Kyoto University and the University of Fukui have discovered that by suppressing the gene USAG-1 antigen, tooth growth is stimulated in mice with a congenital condition where their teeth don’t form.

Unlike humans, mice have only one set of teeth. With a grain and seed based diet, being a toothless mouse suggests the probability of not being a mouse for very long at all.

One of the lead authors of the study, Dr Katsu Takahashi, has acknowledged that the molecules responsible for tooth development had been identified. What has been discovered, is that the creation and form of an individual tooth depends on several molecule interactions – including bone morphogenetic protein (BMP), and protein signalling pathways (Wnt).

The involvement of BMP and Wnt are much more than simply tooth development.

These molecules modulate the growth of tissue and organs well before a developing human is even the size of a peanut. Drugs affecting this activity affect the entire body.

That’s how the sedative thalidomide, used to treat morning sickness, resulted in birth defects in more than 100,000 babies worldwide. Used in the late 1950s and early ‘60s it interfered with the Bmp/Dkk1/Wnt signalling pathway, the outcome of which was limb deformities. After decades of research, it was established that thalidomide degraded an unexpectedly wide range of transcription factors – cell proteins that help switch genes on or off.

One called SALL4 was completely removed from cells.

Lack of SALL4 disrupts not only limb growth, but a spectrum of foetal development processes, so sadly experienced by the children of mothers prescribed thalidomide during pregnancy.

Such is the critical function of BMP and Wnt.

The Kyoto and Fukui team already knew that suppressing USAG-1 would benefit tooth growth. What was unknown was whether that alone would be enough.

Further experiments with the USAG-1 antibody revealed that BMP signalling determines the number of teeth. Moreover, a single administration was enough to generate an entire tooth.

With no notable side effects, the completed series of trials on mice and then ferrets proved so efficacious the first human trials of the tooth regeneration drug developed by Dr Katsu Takahashi’s team began in September 2024. Thirty men, aged 30 to 64, are participating in the study. If successful, this incredible treatment could be available to the public within five years.

And that’s not all that’s happening in this particular field of regenerative medicine.

In November 2024, in order to continue its studies on the regenerative ability of fish in tooth replacement, the University of Manitoba, Canada opened its $US2.5-million Rady Biomedical Fish Facility to further advance the global dedication to human dental regeneration.

An equally recent advancement is from Tufts University, Massachusetts where a research team was able to bioengineer human-like teeth in pigs.

There’s a convergence of breakthroughs in technology, tissue engineering, regenerative medicine and dentistry that has each branch greatly benefit from this symbiosis in terms of shared knowledge, and condensed time.

The Tufts team’s proto-teeth were created by a combination of human and porcine tissue. Cells of human dental pulp were taken and mixed with pig tooth buds cells. Researchers harvested cells from slaughterhouse pig jaws, which were then grown in the lab. This cellular mixture was seeded onto a tooth-shaped scaffold-like structure made of pig teeth that had been stripped of cells, with just the extracellular matrix left.

This composite material was then transplanted into the gums of Yucatan minipigs; a North American breed known for their docile temperament and test animal suitability.

After these bioengineered tooth bud constructs were implanted they were left to develop for two, and four months. Researchers identified that tooth-like tissue, including tooth-supporting periodontal ligament and hard layers of cementum and dentin had developed in these proto-human-like teeth.

The ability to grow living tissue teeth with properties similar to natural teeth would be a significantly improved treatment choices for tooth loss. Certainly, it would have greater durability than even titanium implants with either porcelain or zirconia crowns, currently considered one of the better options with a 10-to-15 year longevity. Tooth regeneration would completely negate the potential and real risks of jawbone resorption and peri-implantitis, common failure factors of dental implants.

Biologically replacing lost teeth is moving further from fiction and closer to reality at quite a rapid rate. Indeed, it will indeed one day make dental implants and synthetic options obsolete. It’s a future many of us will experience.

Until then, the best course of action is keeping the teeth you already have. Care for them diligently, feel privileged in doing so, and see your dentist.

Don’t make that the adynaton.

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