Multiple bacteria types found to contribute to bone loss in gum disease

 

IMAGE: THE DATA EXPRESSED AS THE MEAN ± SEM OF 6 MICE. A SIGNIFICANT DIFFERENCE BETWEEN THE TWO GROUPS WAS INDICATED; *P<0.05 AND **P<0.01 VS PBS, BY STUDENT’S T-TEST. SCALE BAR INDICATED 1 MM. view more 

CREDIT: MASAKI INADA / TUAT

Mouths are filthy, harboring the second largest microbiome of the human body. Some bacteria can help break down food, among other responsibilities; other bacteria can travel into the mouth on food, fingers, pen caps and more to contribute to gum disease and other oral infections. More than good or bad bacteria, researchers have now unveiled that positive and negative bacterium are responsible for periodontitis symptoms — Gram-positive and Gram-negative, that is.

Gram-positive bacteria have thicker cell walls that retain the purple color from Gram stain, which can quickly differentiate cell types based on the width of their cell walls. For the first time, researchers found that Gram-positive bacteria can also induce the resorption of the bone that holds teeth in place, called the alveolar bone. The results were published on June 25 in Scientific Reports.

“This finding is a new concept: both Gram-positive and -negative bacteria are involved in the progression of periodontal bone loss,” said lead author Masaki Inada, associate professor in the Department of Biotechnology and Life Science at the Tokyo University of Agriculture and Technology (TUAT). “In a healthy condition, the tooth root is embedded into a socket in the alveolar bone in periodontal tissue. Infection of mixed multiple Gram-negative bacteria resulted in alveolar bone resorption and tooth loss induced by severe inflammation in periodontal tissues. It is well-known that the major pathogens of periodontitis are dominantly gram-negative bacteria. It was unclear whether gram-positive bacteria are associated with or contribute to the progression of periodontal bone loss.”

In a previous study, the researchers injected lipopolysaccharide (LPS) from Gram-negative bacteria into mice engineered without the gene that produces molecules that gather at sites of damaged tissue. Without these molecules, called prostaglandin E2 (PGE2), the LPS failed to induce bone loss. This suggested, Inada said, that PGE2 is required for periodontitis to progress.

“LPS is considered to be a dominant pathogen causing inflammatory bone resorption in periodontitis,” Inada said. “On the other hand, Gram-positive bacteria have been known to contribute to the inflammation of the periodontal gums in the initial phases of periodontitis; however, there was little evidence to show that these pathogens contribute to the induction of inflammatory bone resorption in the late phase of periodontitis.”

It comes down to bone remodeling, according to Inada. At what point does cell death from the infection outpace the body’s effort to create new bone cells?

“Several reasons could be counting and explaining on these phenomena, “ Inada said.

In the case of LPS in the PGE2-deficient mice, the balance stayed in favor of bone formation. But when the researchers introduced lipoteichoic acid (LTA), a major component of the cell wall in Gram-positive bacteria, the balance tipped to bone resorption. The researchers injected mice with periodontitis with LTA and found that it increased the amount of PGE2, resulting in bone resorption. They also saw that Gram-positive bacteria proliferated at a higher rate than Gram-negative bacteria and they preferred to occupy the depths of the teeth pockets — suggesting a more potent dose of LTA closer to the site of bone lose, according to Inada.

“Our goal is to clarify the crosstalk of Gram-positive and -negative bacteria for the pathogenesis and progression of periodontal bone loss,” Inada said. “The understanding of the mechanisms will contribute to developing novel drugs for the treatment of periodontal bone loss.”

Getting to the root of tooth replantation challenges

 

Peer-Reviewed Publication

TOKYO MEDICAL AND DENTAL UNIVERSITY

PrintEmail App

 

IMAGE: EXCESSIVE INFLAMMATION AFTER TOOTH REPLANTATION INDUCES SEVERAL OMPLICATIONS INCLUDING ROOT RESORPTION, TERMINATION OF ROOT FORMATION AND PULP NECROSIS, CAUSED BY EXCESSIVE INFLAMMATION. NF-KB DECOY ODN-LOADED PLGA NANOSPHERE INHIBITS POST-OPERATIVE INFLAMMATION, THUS ENHANCES PERIODONTAL REGENERATION, INCLUDING REDUCTION OF ROOT RESORPTION, AND CONTINUATION OF ROOT FORMATION. view more 

CREDIT: DEPARTMENT OF ORTHODONTIC SCIENCE, TMDU

Researchers from Tokyo Medical and Dental University (TMDU) report a delivery system that promotes healing in tooth replantation in rats

 Tokyo– Completely dislodging a tooth from the socket is not generally considered a reversible process. However, this injury is most common in children, whose roots may not be completely developed, meaning quick reactions could save the tooth. Researchers are continually looking to increase the chance of success in tooth replantation. Now, a team led by researchers from Tokyo Medical and Dental University (TMDU) has reported a gene delivery system that promotes the healing process in a rat model. Their findings are published in Journal of Periodontology.

Replanting a tooth as quickly as possible after it is knocked out provides its best chance of survival. Speed ensures that the periodontal ligament (PDL)—the tissue that holds the tooth in place—and dental pulp do not start to die. Fibers can then reattach, and the blood vessels and pulp tissue can continue to grow and support the tooth.

However, many factors can affect the success of replantation—for example, inflammation—which can stop the PDL regenerating.

One of the messaging pathways that controls inflammation is the nuclear factor-kappa B (NF-κB) pathway. Activation of this pathway produces the proteins that induce inflammation. And inflammation leads to osteoclasts—bone degrading cells—breaking down the tissue around the root of the tooth, often spelling the end of any hope of successful replantation.

A recently reported way of stopping the NF-κB pathway is to use NF-κB decoy oligodeoxynucleotides (ODNs), which prevent NF-κB biding to its target genes. However, getting the large NF-κB decoy ODNs to where they need to be to have an effect can be challenging.

The TMDU researchers loaded NF-κB decoy ODNs into poly(lactic-co-glycolic acid) nanospheres to give NF-PGLA. Incorporating the therapeutic cargo into the nanosphere system protected it until it reached the site of action.

“We tested our delivery system in rats by immersing extracted incisors in different solutions before replanting them,” explains study first author Kai Li. “We found that the teeth treated with NF-PGLA showed significantly greater dental root thickness, which is necessary for successful replantation.”

The researchers also found that no root resorption—dissolving of the tooth root—was observed 7 days after treatment with NF-PGLA. In addition, there were fewer osteoclasts 7 and 14 days after replantation for NF-PGLA-treated teeth.

“Application of our NF-PGLA system encouraged the healing process by preventing the exacerbation of inflammation,” says study corresponding author Yuji Ishida. “We believe that our delivery system will contribute to significantly improving the success of tooth replantation in the clinic,” adds principal investigator Takashi Ono.

The study, “Nuclear factor-kappa B (NF-κB) decoy oligodeoxynucleotide-loaded poly lactic-co-glycolic acid (PLGA) nanospheres promote periodontal tissue healing after tooth replantation in rats”, was published in Journal of Periodontology at DOI: 10.1002/JPER.21-0134.
 

Smart dental implants

Geelsu Hwang of the University of Pennsylvania and colleagues are developing a smart dental implant that resists bacterial growth and generates its own electricity through chewing and brushing to power a tissue-rejuvenating light.

Peer-Reviewed Publication

UNIVERSITY OF PENNSYLVANIA

PrintEmail App

More than 3 million people in America have dental implants, used to replace a tooth lost to decay, gum disease, or injury. Implants represent a leap of progress over dentures or bridges, fitting much more securely and designed to last 20 years or more.

But often implants fall short of that expectation, instead needing replacement in five to 10 years due to local inflammation or gum disease, necessitating a repeat of a costly and invasive procedure for patients.

“We wanted to address this issue, and so we came up with an innovative new implant,” says Geelsu Hwang, an assistant professor in the University of Pennsylvania School of Dental Medicine, who has a background in engineering that he brings to his research on oral health issues.

The novel implant would implement two key technologies, Hwang says. One is a nanoparticle-infused material that resists bacterial colonization. And the second is an embedded light source to conduct phototherapy, powered by the natural motions of the mouth, such as chewing or toothbrushing. In a paper in the journal ACS Applied Materials & Interfaces and a 2020 paper in the journal Advanced Healthcare Materials, Hwang and colleagues lay out their platform, which could one day be integrated not only into dental implants but other technologies, such as joint replacements, as well.

“Phototherapy can address a diverse set of health issues,” says Hwang. “But once a biomaterial is implanted, it’s not practical to replace or recharge a battery. We are using a piezoelectric material, which can generate electrical power from natural oral motions to supply a light that can conduct phototherapy, and we find that it can successfully protect gingival tissue from bacterial challenge.”

In the paper, the material the researchers explored was barium titanate (BTO), which has piezoelectric properties that are leveraged in applications such as capacitators and transistors, but has not yet been explored as a foundation for anti-infectious implantable biomaterials. To test its potential as the foundation for a dental implant, the team first used discs embedded with nanoparticles of BTO and exposed them to Streptococcus mutans, a primary component of the bacterial biofilm responsible for tooth decay commonly known as dental plaque. They found that the discs resisted biofilm formation in a dose-dependent manner. Discs with higher concentrations of BTO were better at preventing biofilms from binding.

While earlier studies had suggested that BTO might kill bacteria outright using reactive oxygen species generated by light-catalyzed or electric polarization reactions, Hwang and colleagues did not find this to be the case due to the short-lived efficacy and off-target effects of these approaches. Instead, the material generates enhanced negative surface charge that repels the negatively charged cell walls of bacteria. It’s likely that this repulsion effect would be long-lasting, the researchers say.

“We wanted an implant material that could resist bacterial growth for a long time because bacterial challenges are not a one-time threat,” Hwang says.

The power-generating property of the material was sustained and in tests over time the material did not leach. It also demonstrated a level of mechanical strength comparable to other materials used in dental applications.

Finally, the material did not harm normal gingival tissue in the researchers’ experiments, supporting the idea that this could be used without ill effect in the mouth.

The technology is a finalist in the Science Center’s research accelerator program, the QED Proof-of-Concept program. As one of 12 finalists, Hwang and colleagues will receive guidance from experts in commercialization. If the project advances to be one of three finalists, the group has the potential to receive up to $200,000 in funding.

In future work, the team hopes to continue to refine the “smart” dental implant system, testing new material types and perhaps even using assymetric properties on each side of the implant components, one that encourages tissue integration on the side facing the gums and one that resists bacterial formation on the side facing the rest of the mouth.

“We hope to further develop the implant system and eventually see it commercialized so it can be used in the dental field,” Hwang says.

Whiter teeth, without the burn

Peer-Reviewed Publication

AMERICAN CHEMICAL SOCIETY

PrintEmail App

 

IMAGE: A NEW BLEACHING GEL WHITENED TOOTH SAMPLES BY SIX SHADES, USING A LOW LEVEL OF HYDROGEN PEROXIDE (12%). view more 

CREDIT: ADAPTED FROM ACS APPLIED MATERIALS & INTERFACES 2021, DOI: 10.1021/ACSAMI.1C06774

Most people would like to flash a smile of pearly whites, but over time teeth can become stained by foods, beverages and some medications. Unfortunately, the high levels of hydrogen peroxide in dentists’ bleaching treatments can damage enamel and cause tooth sensitivity and gum irritation. Now, researchers reporting in ACS Applied Materials & Interfaces have developed a gel that, when exposed to near infrared (NIR) light, safely whitens teeth without the burn.

The growing demand for selfie-ready smiles has made tooth whitening one of the most popular dental procedures. Treatments at a dentist’s office are effective, but they use high-concentration hydrogen peroxide (30–40%). Home bleaching products contain less peroxide (6–12%), but they usually require weeks of treatment and don’t work as well. When a bleaching gel is applied to teeth, hydrogen peroxide and peroxide-derived reactive oxygen species (mainly the hydroxyl radical) degrade pigments in stains. The hydroxyl radical is much better at doing this than hydrogen peroxide itself, so researchers have tried to improve the bleaching capacity of low-concentration hydrogen peroxide by boosting the generation of powerful hydroxyl radicals. Because previous approaches have had limitations, Xingyu Hu, Li Xie, Weidong Tian and colleagues wanted to develop a safe, effective whitening gel containing a catalyst that, when exposed to NIR light, would convert low levels of hydrogen peroxide into abundant hydroxyl radicals.

The researchers made oxygen-deficient titania nanoparticles that catalyzed hydroxyl radical production from hydrogen peroxide. Exposing the nanoparticles to NIR light increased their catalytic activity, allowing them to completely bleach tooth samples stained with orange dye, tea or red dye within 2 hours. Then, the researchers made a gel containing the nanoparticles, a carbomer gel and 12% hydrogen peroxide. They applied it to naturally stained tooth samples and treated them with NIR light for an hour. The gel bleached teeth just as well as a popular tooth whitening gel containing 40% hydrogen peroxide, with less damage to enamel. The nanoparticle system is highly promising for tooth bleaching and could also be extended to other biomedical applications, such as developing antibacterial materials, the researchers say.

The authors acknowledge funding from the National Natural Science Foundation of China, the National Key R&D Program of China and the Key Technologies R&D Program of Sichuan Province.

The abstract that accompanies this paper is available here.

Study: Dental implant surfaces play major role in tissue attachment, warding off unwanted bacteria

 

Research lays groundwork for improving the success of medical and dental implants

Peer-Reviewed Publication

 When dental implants are inserted, saliva or blood plasma immediately coat them. The implants adsorb a thin layer of proteins from these fluids that help gum tissue attach, but also allow microorganisms – including potentially harmful bacteria – to grow on the implant surface.

The surface of implants, as well as other medical devices, plays a significant role in the adsorption of oral proteins and the colonization by unwanted microorganisms (a process known as biofouling), according to a new study led by the University at Buffalo and the University of Regensburg.

The research, published in the Journal of Dental Research, sought to increase scientists’ understanding of this complex biological process by examining the makeup of the oral protein layer and how it can be controlled by chemically modifying the biomaterial surface. The findings lay the groundwork for improving the success of medical and dental implants, says co-lead investigator Stefan Ruhl, DDS, PhD, professor of oral biology in the UB School of Dental Medicine.

“It is often this protein layer, rather than the biomaterial surface, that is encountered by colonizing bacteria or attaching tissue cells. These proteins help determine the biological or pathological consequences that result in either long-term survival of the implant or its failure along with irreversible damage to the surrounding tissues from infection,” says Ruhl. “Therefore, it is important to determine how adsorption might be controlled through chemical modification of the biomaterial surface to achieve a desired outcome.”

The study was also co-led by Rainer Müller, PhD, professor at the Institute of Physical and Theoretical Chemistry at the University of Regensburg.

Using silica beads designed in Müller’s lab with various chemically modified surfaces, the researchers found that the adsorption of proteins from blood plasma is more influenced by the amount of protein adsorbed than by the composition of the protein layer.

However, the adsorption of proteins from saliva was directly impacted by the biomaterial’s surface. Adsorption was lower on surfaces that had a negative electric charge or that repelled water, countering the findings of previous studies.

When examining complex biofluids such as saliva and blood, adsorption became unpredictable for the majority of proteins, says Ruhl.

“The interaction between the proteins contained in the biofluids may play an important, but still little understood, role in adsorption processes,” says Müller. “The ultimate goal to connect surface properties to protein adsorption so that optimal tissue compatibility will be achieved but microbial adhesion will be prevented, will likely not be as straightforward as expected.”

The model system of chemically modified silica surfaces developed by the researchers may serve as a platform to study the basic principles of protein adsorption from complex biofluids.

“To improve the design of implant surface coatings, future research should examine the adsorption of proteins that are known to either foster the attachment of tissue cells or colonizing bacteria, as well as explore the molecular structure of complex mixtures of blood plasma and saliva proteins,” says Ruhl.

Jutta Lehnfeld, doctoral candidate at the University of Regensburg, is the first author. Additional UB School of Dental Medicine investigators include alumnus Yegor Dukashin, DDS; alumna Janet Mark, DDS; Gregory White, DDS, volunteer clinical assistant professor; and alumna Stephanie Wu, DDS. University of Regensburg alumna Verena Katzur, PhD, is also an investigator.

Researchers identify oral bacteria as the major cause for periodontitis, a gum infection causing tooth loss

 

One of the major causes of tooth loss is the inflammation and weakening of the supporting structures of the teeth caused by bacterial infection, a condition commonly known as “periodontitis.” The oral cavity is home to a myriad of microorganisms, including bacteria that generally maintain a “symbiotic” (mutually beneficial) or neutral relationship with the host, but are also capable of initiating many diseases.

Aggregation of the bacterial community into “biofilms” is often associated with the development of infections, including periodontitis. With currently available treatment options often proving inadequate, there is a pressing need to understand the beginning and development of the disease better. Now, in a study published in International Journal of Environment and Public Health Research, a group of researchers led by Assistant Professor Naoki Toyama from Okayama University, Japan, reveal insightful findings that could provide new directions to the treatment strategies for periodontitis.

The physiology of an individual directly affects the development of infection. Genetic differences among hosts contribute to differences in susceptibility to specific pathogens and the chance of developing certain diseases. In their study, Dr. Toyama and colleagues focused on understanding the microbes associated with the presence of periodontitis and the host genetic factors that might facilitate the development of the conditions. Dr. Toyama explains the motivation behind their study, “Several studies on periodontitis have shown that the development of the disease is associated with the nature of the oral microbiome as well as with genetic ‘polymorphism,’ the most common type of genetic variation among people. However, there is no study that simultaneously assesses the importance of these two risk factors in developing the disease.”

Accordingly, the team conducted a cross-sectional study in which they genotypically analyzed 14,539 participants and conducted saliva sampling of 385 individuals. They finally retained 22 individuals for statistical analysis, and based on their periodontal status, divided them into “periodontitis” and “control” groups.

The team found that the “β-diversity” of the microbes, which refers to the ratio between regional and local species diversity, was significantly different between the periodontitis and control groups. Furthermore, they attributed the presence of the bacteria species, P. gingivalis and the bacterial families, Lactobacillaceae and Desulfobulbaceae, to periodontitis. In contrast, they found no relation between genetic polymorphism and periodontitis. Taking these inferences into account, the team concluded that our oral microbiome affects the status of periodontitis more than our genes.

So, how do these findings influence current clinical practices? Dr. Toyama surmises, “The fact that the prevalence of periodontitis is associated with the members of the microbiome rather than the genetic identity of the individual would motivate clinicians to pay more attention to microbiome composition than to host factors in the routine work of periodontal examination, and design customized treatment strategy for periodontitis.’’

As for us common folks, these findings further reinforce the importance of regular tooth cleaning in keeping periodontitis at bay.