Periodontitis is widespread and can have serious consequences for overall health. Researchers at Fraunhofer have identified a substance that selectively inhibits only those bacteria that cause periodontitis, thereby preserving the natural balance of the oral microbiome. This technology has been further developed and commercialized as a range of oral care products by the spin-off company PerioTrap.
The oral microbiome is home to more than 700 different bacterial species, of which only a few can cause periodontitis. These adhere to dental plaque, particularly along the gum line, where they trigger inflammation (gingivitis). This can potentially lead to chronic periodontitis, which does more than just cause receding gums and loose teeth: If these bacteria enter the bloodstream, they can also contribute to the development of diabetes, rheumatic disease, arthritis, cardiovascular disease, chronic inflammatory bowel disease and even Alzheimer’s disease.
Pathogenic bacteria are killed by conventional oral care products such as alcohol-based mouthwashes and products containing the antiseptic chlorhexidine, but these also eliminate beneficial microorganisms. When the oral microbiome re-establishes itself after treatment, pathogenic bacteria such as Porphyromonas gingivalis gain an early advantage because they proliferate particularly well in inflamed gum tissue. Beneficial bacteria grow more slowly, and the oral microbiome quickly shifts back from its natural balance into dysbiosis, allowing the disease to recur.
Researchers at the Halle branch of the Fraunhofer Institute for Cell Therapy and Immunology IZI have identified a substance that selectively blocks harmful pathogens such as Porphyromonas gingivalis without affecting other bacteria. Stephan Schilling, Head of the Fraunhofer IZI branch Molecular Drug Biochemistry and Therapy Development, explains the specific mode of action of the substance, which is known as guanidinoethylbenzylamino imidazopyridine acetate: “Rather than simply killing gingivitis pathogens, it inhibits their growth. They are unable to exert their toxic effects, so beneficial bacteria can occupy niches that would otherwise be inaccessible to them. In this way, the substance works in harmony with healthy bacteria to gently rebuild and stabilize the microbial balance in the mouth,” says Schilling.
The basis for this technology originated from an EU-funded project involving numerous international partners. The spin-off company Periotrap Pharmaceuticals GmbH was founded in Halle in 2018 with the aim of developing innovative oral care products. PerioTrap created its microbiome-friendly toothpaste in close collaboration with Fraunhofer IZI and the Fraunhofer Institute for Microstructure of Materials and Systems IMWS. “The product is designed to prevent periodontitis. Like conventional toothpaste, it also contains abrasives and fluoride to prevent tooth decay,” explains Mirko Buchholz, one of the spin-off’s founders.
Overcoming the technological challenges required extensive experimentation to develop the substance identified at Fraunhofer IZI into an ingredient with all the necessary properties. The product has to be able to block harmful bacteria without being toxic, it must not be absorbed by the body or enter the bloodstream and it should not cause tooth discoloration.
The Fraunhofer IZI team conducted biochemical analyses and structural biology studies to support product development. “This allows us to gain a better understanding of how the substances work and determine the optimum composition of the toothpaste’s active ingredients,” Schilling explains. Fraunhofer IZI has many years of experience in identifying and testing substances suitable for targeting pathological mechanisms or pathogens, such as those that cause infectious diseases.
Meanwhile Fraunhofer IMWS contributed its materials science expertise, testing the effects of each new toothpaste formulation on teeth and gums. As Andreas Kiesow explains, Group Manager Characterization of Medical and Cosmetic Care Products: “Scanning electron microscopy, chemical characterization and quantitative measurements enable us to draw detailed conclusions about a substance’s compatibility and function. To put it simply: We ultimately find out whether the toothpaste works or not.”
Researchers at both Fraunhofer institutes conducted the project in accordance with Good Laboratory Practice (GLP) quality standards. This enables testing of ingredients and active substances subject to rigorous, officially recognized conditions, with results that are recognized by national and international authorities. “Compliance with GLP guidelines was a key element of the project. We didn’t just develop a good toothpaste with a new ingredient: we developed a high-quality oral care product of medical-grade standard,” says Schilling.
Development of the technology is ongoing. For its use in dental practices, experts at the PerioTrap spin-off have worked with the Fraunhofer institutes to develop a care gel that is applied after professional dental cleaning. This blocks pathogenic bacteria, stabilizes the oral microbiome and keeps the gums supple.
The PerioTrap technology is also to be used to develop additional products for oral and dental care. Researchers are currently working on a mouthwash, for example, as well as products for other markets.
Pets may benefit from improved oral care in the future, as well: since the disease has very similar causes in dogs and cats, pet care products are likewise on the agenda.
Fraunhofer-Gesellschaft