A tooth is made up of three layers: retention (inner), tooth (middle), and enamel (outer). Enamel is the hardest substance in the human body, and protects the tooth from external damage. But it has one bad feature: after the teeth develop in childhood, the enamel cannot regenerate. Any injury is permanent. That's why we have fillings, crowns, implants. But a new study published in the International Journal of Oral Science (Nature group) of the University of Washington presents a breakthrough: an AI-designed protein that can make enamel cells mature in the laboratory and produce real enamel-like.
Why is enamel so hard to imitate?
Ameloblast cells are the cells that produce enamel. They are active only in childhood, during the development of the teeth. Then they die or fade away. For years, scientists tried to "revive" them in the laboratory, but without success: the cells did not mature to the right stage, and certainly did not manage to produce the hard enamel.
The main reason: ameloblast cells need a specific signal from other cells in the tooth. This letter is called "Delta", and it appears appropriately in the name of odontoblasts. Without it, ameloblast cells do not know that they need to mature.
The solution: a protein designed by AI
The University of Washington team, through the Institute for Stem Cell & Regenerative Medicine (ISCRM), was able to solve the problem with a new approach: They designed a protein on a computer that mimics the Delta signal. This is a great example of how AI is changing biology.
The protein, called "soluble Notch agonist" (soluble agonist for the Notch pathway), bypasses the need for a signal from odontoblasts cells. It directly activates the pathway in ameloblast cells, causing them to mature into a new phase identified in the study: "WDR72-positive mature secretory ameloblast" or ismAM for short.
The mouse experiment: creating enamel-like in a living body
The team was not satisfied with the laboratory. They implanted the organoids (groups of adult ameloblast cells) under the kidney capsule of mice. After a few weeks, the cells formed a calcified substance similar to enamel. This is the first time enamel-like has actually been created in a living body using this approach.
Where does it go?
The next step is to increase the process. The researchers plan:
- Combination with Dentin. Email alone is not enough. You also need the inner tooth. The next step: to create a more complex organoid
- Transplantation in more complex models. Now it is under the kidney capsule. The next step: implantation in an animal's jaw
- Safety tests. Mainly a fear of cancer, because stem cells can become uncontrollable
The researchers estimate: clinical trials in humans can begin in 5-7 years. Self-regenerating teeth could be available in 2035-2040.
What does this mean for dentistry?
If the treatment is successful, it will replace:
- Fillings (enamel-like production instead of the filling)
- Crowns (full regeneration of a tooth)
- Implants (implantation of stem cells instead of metal)
- Dental prostheses
It could also change the treatment of amelogenesis imperfecta, a genetic disease that causes enamel to be defective from birth. In the study it was identified that a gene called DLX3 is critical for the production of enamel. A change in this gene is the cause of the disease.
Additional applications
Renovating teeth is just the beginning. The technology of AI-designed proteins for the activation of cell pathways can also be used for:
- Bone renewal (osteoporosis)
- Skin renewal (wounds, scars)
- Cartilage renewal (osteoarthritis)
- Hair renewal
The bottom line
For years, dentistry was considered a "boring field" of minimal innovation. This study changes the picture. With the combination of AI, cellular biology, and protein design, we are not far from the day when clogging will be a thing of the past. The tooth will repair itself.
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