Many studies have explored the possibility of regenerating natural teeth in recent years. We review the research to determine how and when tooth regrowth might be possible in the future.
According to the World Health Organization, the global prevalence of complete tooth loss stands at 7% among those aged 20 and over. For those over 60, the percentage rises to 23%. In the UK, the government estimates that 5% of adults over 16 have no natural teeth.
Currently, there is no publicly available method for regrowing 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 for the tooth rather than a natural regrowth.
However, the possibility of regrowing or regenerating natural teeth has been explored by several previous studies. Mechanisms such as RNA, stem cells and mineral regeneration have all seen various degrees of success in repairing or replacing damaged teeth.
In July 2023, researchers from the Medical Research Institute Kitano Hospital in Osaka, Japan announced the development of a new tooth regrowth medicine. It uses RNA to administer antibodies against a molecule called USAG-1 which inhibits bone growth proteins.
Development of the medicine took approximately eight years, beginning in 2005.
Katsu Takahashi is lead researcher and head of the dentistry and oral surgery department at the Medical Research Institute Kitano Hospital. His research is based on the idea that humans once grew a third set of teeth following the milk and adult dentition. Dr Takahashi said that humans lost the ability to generate this third set of teeth over time but still possess the ‘buds’ from which they develop.
The presence of the USAG-1 molecule prevents potential tooth germs from forming into full teeth. It exists to regulate the number of teeth that healthy adults develop. Researchers hope that suppressing this molecule could lead new teeth to be grown from the vestigial ‘buds’.
This will particularly help those with congenital edentulism, a condition which causes sufferers to be born with fewer teeth than normal. However, the researchers hope that the drug will also be effective in patients who have lost teeth due to gum disease or injury.
Dr Takahashi said: ‘We’re hoping to see a time when tooth regrowth medicine is a third choice alongside dentures and implants.’
Initial animal trials of the medicine were highly successful with no notable side effects. It was found to promote the growth of ‘third generation’ teeth in mice, ferrets and dogs.
(Photo: Medical Research Institute Kitano Hospital)
The drug was scheduled to begin human testing at Kyoto University Hospital from September 2024.
The human trials involve healthy adults with at least one missing tooth being injected with the medicine and observed. This will establish whether any negative health effects result from human use.
Once the safety of the drug is confirmed, researchers will test it on children aged two to seven with four or more missing teeth.
Following the clinical trials, the research team plans to have the medicine ready for general use in 2030. If successful, they believe the tooth regrowth medicine 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 confident I’d be able to make it happen.’
The Osaka researchers were prompted by a desire to offer a solution for tooth loss that is permanent. While long-term replacements such as dental implants can be close to permanent, there are currently no treatments available which regenerate natural dentition.
Dr Takahashi said: ‘We want to do something to help those who are suffering from tooth loss or absence. While there has been no treatment to date providing a permanent cure, we feel that people’s expectations for tooth growth are high.’
Another method of tooth regrowth which has been researched in recent years is stem cell regeneration.
In October 2023, academics from Sharad Pawar Dental College and Hospital, India reviewed the existing research and concluded that whole tooth regeneration with stem cells was a ‘realistic aim’.
The study concluded that stem cells were particularly useful for bone regeneration and correction of bone abnormalities. This would be highly applicable to restorative dentistry cases to correct craniofacial bone damage from trauma.
Researchers also said that stem cell therapy could assist with regeneration of soft tissue within the mouth.
In August 2023, a research team succeeded in creating stem-cell based organoids that secrete the proteins which form dental enamel. Led by scientists from the University of Washington School of Dentistry, the researchers consider this breakthrough to be ‘critical first step’ in developing stem-cell-based treatments to repair damaged teeth.
The team said it hoped to use this research to create an enamel that is as durable as that found in 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, a professor of biochemistry, headed the project. She said: ‘Many of the organs we would like to be able to replace, like human pancreas, kidney, and brain, are large and complex. Regenerating them safely from stem cells will take time.
‘Teeth on the other hand are much smaller and less complex. They’re perhaps the low-hanging fruit. It may take a while before we can regenerate them, but we can now see the steps we need to get there.
‘This may finally be the “century of living fillings” and human regenerative dentistry in general.’
While these trials have seemed promising, the potential for tooth regeneration through stem cells does raise some ethical concerns.
David Obree, Archie Duncan fellow in medical ethics at the University of Edinburgh, spoke to Dentistry.co.uk about the potential implications of tooth regrowrth. He described stem cell regeneration as ‘an exciting development which is likely to revolutionise dentistry and medicine in general’. However, he also named the source of 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 tissues 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 use of ‘autologous stem cells’, or those taken from patients themselves, would mitigate this concern. He added: ‘As well as obviating ethical concerns there is less chance of immunological rejection.
‘It may be that cells taken from extracted deciduous or wisdom teeth will be the pluripotent stem cells of choice, both for teeth and other organ renewal, and thus an interesting side-line for dentists harvesting the cellular material’
Another issue raised by Dr Obree is that of cost. He asks: ‘Will this be an expensive treatment only available to the rich, or will the technology be cheap and available to everyone?’
It is currently unclear how expensive stem cell treatments would be when available to the public and if offering them on the NHS would be possible.
An alternative approach to tooth regrowth is mineral regeneration to repair damaged enamel.
In 2019, a gel was developed by mixing calcium and phosphate ions in an alcoholic solution with the organic compound trimethylamine. This solution successfully produced clusters of calcium phosphate, the main component of dental enamel.
When applied to damaged tooth samples, the gel was found to create a three-micrometre-thick layer of new enamel 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 realise tooth enamel regrowth without using fillings which contain totally different materials.’
The materials used within the trial are cheap and can be prepared on a large scale.
Dr Liu continued: ‘After intensive discussion with dentists, we believe that this new method can be widely used in future.’
Results from studies have been positive about the potential for regenerating damaged teeth. Despite this, there are still significant barriers to whole tooth regrowth.
For example, the use of RNA to induce tooth regrowth has so far only been successful in patients who are born with missing teeth. While these patients are likely to be able to access the new medicine by 2030, this will not assist those who lose teeth later in life.
On the other hand, researchers said they were hopeful that further investigation could broaden the application of the medication 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 immunological rejection.
However, transplant rejection was found to be uncommon across several studies when adult stem cells taken from organs such as tooth pulp or umbilical cords were used. The 2023 review concluded that oral and facial treatment was possible with adult stem cells from many different organs.
Overall while studies have shown positive results for potential methods of tooth regeneration, there is no clear timeline for if and when it will be possible to regrow whole teeth.
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