Synthetic saliva prepared from sugarcane protein shields teeth from acid and decay

By Morgan Nwanguma

A newly developed sugarcane-derived protein could soon offer tooth protection similar to natural saliva – especially for people whose bodies no longer produce enough of it.

Scientists have engineered an artificial saliva using a modified sugarcane protein known as CANECPI-5. This protein attaches directly to tooth enamel, forming a protective barrier that helps defend against acid damage and harmful bacteria. Early studies show that its effectiveness improves when combined with fluoride and xylitol, significantly reducing tooth decay. The innovation may be particularly beneficial for cancer patients who experience reduced saliva production after treatment.

Designed as a mouthwash, this artificial saliva targets individuals with head and neck cancer, who often undergo radiotherapy that damages salivary glands. Since saliva is essential for regulating oral bacteria and maintaining dental health its loss can lead to severe complications.

Researchers at the Bauru School of Dentistry at the University of São Paulo (FOB-USP) in Brazil discovered that CANECPI-5 forms a protective “shield” over teeth. This layer helps guard enamel against acids from foods and drinks such as fruit juices and alcohol, as well as acids that may come from the stomach. The study was published in the Journal of Dentistry.

The research was led by doctoral candidate Natara Dias Gomes da Silva at FOB-USP and involved collaboration with scientists from the Federal University of São Carlos (UFSCar), the University of California in San Francisco, and Yonsei University College of Dentistry in South Korea.

The research is part of the Thematic Project “Modulation of acquired pellicle to control dental mineral loss: unveiling mechanisms to make therapies possible,” coordinated by Professor Marília Afonso Rabelo Buzalaf at FOB-USP.

“We tested the mouthwash developed with CANECPI-5 by applying this solution to small pieces of animal teeth once a day for one minute. Based on these results, we’ll conduct further research so that we can think about applications of this product,” Silva, the first author of the article said.

How Synthetic Saliva Reinforces Tooth Enamel

“This is the first product that uses the concept of acquired pellicle [a thin protective layer that quickly forms on the tooth surface] to treat xerostomia, which is the sensation of a dry mouth caused by a lack of saliva. We use substances that will reformulate the composition of the proteins that bind to the teeth,” Buzalaf clarifies.

“We’ve developed a process in which CANECPI-5 binds directly to tooth enamel, helping to make teeth more resistant to the action of acids produced by bacteria,” Silva said.

The study found that CANECPI-5 is most effective when used alongside fluoride and xylitol. In tests, the artificial saliva spray lowered bacterial activity and slowed tooth demineralization – the loss of calcium and phosphate that weakens teeth and increases the risk of cavities.

A Promising Option for Post-Treatment Dental Damage
This breakthrough is particularly significant because there is currently no specialized treatment for the severe tooth decay commonly experienced after radiation treatment for head and neck cancer.

“Artificial saliva improves the sensation of dry mouth and sores. This helps with discomfort and also combats bacteria. In some cases, the use of this type of product is only for a short time. In others, it’s permanent, because many individuals lose the ability to produce saliva,” adds Buzalaf.

The CANECPI-5 protein has since been patented. The next stage is to expand production by collaborating with companies interested in bringing the know-how to market.

“We’ve already tested the solution as a mouthwash, gel, and orodispersible film, which is a type of plastic that’s placed on the tongue and dissolves, releasing the protein. We’ve tested it in several vehicles and found that CANECPI-5 works very well in all of them. We’ll continue testing other technologies within the Thematic Project to use not only this protein, but others as well,” says Buzalaf.

From Sugarcane Research to CANECPI-5
Flávio Henrique Silva, a professor in the Department of Genetics and Evolution at UFSCar and a contributor to the development of CANECPI-5, explained that the discovery builds on earlier studies of cystatins – a group of proteins involved in multiple biological functions. This foundational work was carried out under the Sugarcane Genome Project (SUCEST, FAPESP).

“At that time, our group identified and produced, in a recombinant form in bacteria, the first cystatin from sugarcane. We named it CANECPI-1. We then identified and produced five other cane cystatins, including CANECPI-5, which had potent inhibitory activities against cysteine peptidases, which are its target enzymes. Throughout our work, we noticed that this protein bound strongly to smooth surfaces, such as the quartz cuvettes used in activity measurements. This led us to conduct tests in partnership with Professor Marília Buzalaf on the binding of the protein to tooth enamel.”

Scientists say CANECPI-5 is particularly promising since it both protects enamel and aids to regulate oral bacteria, making it important for future dental therapy.

“CANECPI-5 has also been used in the work of other colleagues in the field of dentistry, particularly involving periodontitis. We also have a collaborative project with a colleague from the Federal University of Uberlândia, using subcutaneous sponge implants in mice, which has shown that it’s capable of reducing inflammation and promoting angiogenesis [the formation of new blood vessels] and fibrinogenesis [the formation of fibrin, a protein essential for blood clotting], important processes in tissue repair, making it a candidate molecule for use in wound healing,” Silva stated.

Next Stages for Man-made Saliva and Dental Applications
As part of the ongoing Thematic Project, researchers will further study how CANECPI-5 interacts with other compounds.

According to Buzalaf, one approach is to combine CANECPI-5 with a peptide derived from statherin, a natural saliva protein to see if the pairing can offer stronger protection against acids from the stomach. The team also plans to explore its potential in preventing periodontal (gum) disease.

“Another aspect of the Thematic Project is to associate CANECPI-5 with vitamin E because this vitamin acts as a carrier, bringing the protein into contact with the tooth. We imagine that this could facilitate the application of the product directly by the patient at home,” says the scientist.

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