Tooth regeneration in adults: what we know so far

Many studies have investigated the regeneration potential of natural teeth in recent years. We review the research to determine how and when regrowth of teeth may be possible in the future.

According to the World Health Organization, the global prevalence of complete tooth loss is 7% among people aged 20 years and older. For those over 60, the percentage rises to 23%. In the UK, the government estimates that 5% of adults over the age of 16 have no natural teeth.

Currently, there is no publicly available method to regrow lost or damaged teeth. The most common solutions for tooth loss are dental implants, dental bridges and dentures. All of these options involve an artificial replacement of the tooth rather than a natural regeneration.

However, the possibility of regenerating or regenerating natural teeth has been investigated by many previous studies. Mechanisms such as RNA, stem cells, and mineral regeneration have all seen varying degrees of success in repairing or replacing damaged teeth.

Whole tooth regeneration with RNA

In July 2023, researchers from Kitano Hospital Medical Research Institute in Osaka, Japan announced the development of a new drug for tooth regeneration. It uses RNA to deliver antibodies against a molecule called USAG-1, which inhibits bone growth proteins.

Development of the drug took about eight years, starting in 2005.

How does the drug regenerate teeth?

Katsu Takahashi is a principal investigator and head of the department of dentistry and oral surgery at Kitano Hospital Medical Research Institute. His research is based on the idea that humans once developed a third set of teeth following milk and the adult dentition. Dr. Takahashi said that humans have lost the ability to create this third set of teeth over time, but still have the “buds” from which they grow.

The presence of the USAG-1 molecule prevents potential dental germs from forming in full teeth. It exists to regulate the number of teeth that healthy adults develop. The researchers hope that suppressing this molecule could lead to the growth of new teeth from the remaining ‘buds’.

This will especially help those with congenital odontitis, a condition that causes sufferers to be born with fewer teeth than normal. However, researchers hope the drug will also be effective in patients who have lost teeth due to gum disease or injury.

Dr. Takahashi said: “We hope to see a time when medicine for tooth regeneration is a third option along with dentures and implants.”

What has happened to clinical trials?

The drug was scheduled to begin human trials at Kyoto University Hospital from September 2024.

Human trials involve healthy adults with at least one missing tooth injected with the drug and observed. This will determine if any adverse health effects result from human use.

Once the safety of the drug is confirmed, researchers will test it in children aged two to seven with four or more missing teeth.

When will the tooth regeneration drug be available?

After clinical trials, the research team plans to have the drug ready for general use in 2030. If successful, they believe the tooth regeneration drug could be a “game changer” for dentistry.

Dr. Takahashi said: “The idea of ​​growing new teeth is every dentist’s dream. I’ve been working on this since I was a graduate student. I was sure I would make it.”

The Osaka researchers were motivated by the desire to provide a solution to tooth loss that is permanent. While long-term replacements such as dental implants can be nearly permanent, there are currently no treatments available that regenerate the natural dentition.

Dr Takahashi said: “We want to do something to help those who suffer from missing or missing teeth. Although there has been no treatment to date that provides a permanent cure, we believe that people’s expectations for tooth growth are high.’

Stem cells for tooth regeneration

Another method of tooth regeneration that has been researched in recent years is stem cell regeneration.

In October 2023, academics from India’s Sharad Pawar Dental College and Hospital reviewed existing research and concluded that total tooth regeneration with stem cells was a “realistic goal”.

The study concluded that stem cells were particularly useful for bone regeneration and correction of bone abnormalities. This could be largely applied in cases of restorative dentistry to correct craniofacial bone damage from trauma.

The researchers also said that stem cell therapy could help regenerate soft tissues inside the mouth.

Can enamel grow back?

In August 2023, a research team succeeded in creating stem cell-based organoids that secrete the proteins that form tooth enamel. Led by scientists from the University of Washington School of Dentistry, the researchers see this discovery as a “critical first step” in developing stem cell-based therapies to repair damaged teeth.

The team said they hoped to use this research to create an enamel that is as durable as that found on natural teeth. The enamel could be created in laboratories and used to fill cavities or applied as a “living filling” to grow into the cavity.

Hannele Ruohola-Baker, professor of biochemistry, led the project. He said: “Many of the organs we would like to be able to replace, such as the human pancreas, kidneys and brain, are large and complex. Safely regenerating them from stem cells will take time.

“Teeth on the other hand are much smaller and less complex. It’s probably the low-hanging fruit. It may take a while before we can regenerate them, but now we can see the steps we need to take to get there.

“This may ultimately be the ‘century of living fillings’ and of human regenerative dentistry in general.”

Ethics of stem cell regeneration

Although these trials looked promising, the possibility of regenerating teeth through stem cells raises some ethical concerns.

David Obree, Archie Duncan Fellow in Medical Ethics at the University of Edinburgh, spoke to Dentistry.co.uk about the potential consequences of tooth regeneration. He described stem cell regeneration as “an exciting development that is likely to revolutionize dentistry and medicine in general.” However, he also cited the source of the stem cells used and their cost as potential ethical issues.

He said: “Much of the early research has been done using embryonic stem cells, that is tissue taken from embryos, either mammalian or specifically human embryos, where there are obvious ethical issues, as there would be if other mammalian cells became implantable. ‘

However, Dr Obree suggested that the use of “autologous stem cells”, or those taken from the patients themselves, would alleviate this concern. He added: “Apart from avoiding ethical concerns, there is less chance of immune rejection.

“It may be that cells obtained from extracted deciduous teeth or wisdom teeth are the pluripotent stem cells of choice, both for teeth and for the regeneration of other organs, and thus an interesting sideline for dentists who harvest the cellular material.”

Another issue raised by Dr. Obree is that of cost. He asks: “Will this be an expensive treatment available only to the rich, or will the technology be cheap and available to everyone?”

It is currently unclear how expensive stem cell treatments will be when they become available to the public and whether they can be offered on the NHS.

Mineral enamel repair

An alternative approach to tooth regeneration is mineral regeneration to restore damaged enamel.

In 2019, a gel was developed by mixing calcium ions and phosphate ions in an alcoholic solution with the organic compound trimethylamine. This solution successfully produced clusters of calcium phosphate, the main component of tooth enamel.

When applied to damaged tooth samples, the gel was found to create a layer of new enamel three micrometers thick in 48 hours. According to the researchers, this repair “would be permanent.”

Zhaoming Liu co-authored the study with colleagues from the Zhejiang University School of Medicine. He said: “Our newly regenerated enamel has the same structure and similar mechanical properties as native enamel.

“We hope to re-develop tooth enamel without using fillings that contain completely different materials.”

The materials used in the test are cheap and can be manufactured on a large scale.

Dr Liu continued: “After intensive discussion with dentists, we believe that this new method can be widely used in the future.”

Will we ever be able to grow teeth again?

Results from studies have been positive for the possibility of regeneration of damaged teeth. Despite this fact, there are still significant obstacles to the complete regeneration of teeth.

For example, using RNA to induce tooth regeneration has so far only been successful in patients born with missing teeth. While these patients are likely to have access to the new drug by 2030, it will not help those who lose teeth later in life.

On the other hand, the researchers said they are optimistic that further research could broaden the drug’s application to those who have lost teeth due to gum disease or injury.

Stem cell regeneration also raises some concerns, including the ethics of using embryonic stem cells and the potential for immune rejection.

However, graft rejection was found to be uncommon in several studies when adult stem cells obtained from organs such as dental pulp or umbilical cord were used. The 2023 review concluded that treatment of the mouth and face was possible with adult stem cells from many different organs.

Overall, while studies have shown positive results for potential tooth regeneration methods, there is no clear timeline as to whether and when it will be possible to regrow entire teeth.

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