Dentistry study presents “positive stress” to boost tooth tissue regeneration

 

IMAGE: DR WARUNA L. DISSANAYAKA AND HIS RESEARCH TEAM BELIEVE THESE NEW FINDINGS WILL PROMOTE THE DEVELOPMENT OF NEW STRATEGIES TO ENHANCE THE THERAPEUTIC POTENTIAL OF TOOTH STEM CELLS. view more 

CREDIT: THE UNIVERSITY OF HONG KONG

Stress is typically thought of as a negative phenomenon, but researchers at HKU Dentistry found “positive stress” that can induce good changes in tooth stem cells to make them more resistant to injury and disease.

The study, published online in the Journal of Dental Research, is the first to show that adaptive mechanisms in tooth stem cells induced by preconditioning to stress can boost the tooth pulp tissue regeneration. The researchers found that oxidative stress caused by low-oxygen environment can elicit a protective response to make tooth stem cells less vulnerable to harm.

When a tooth is damaged, either by serious decay or injury, the living tissue inside becomes exposed to harmful bacteria and vulnerable to infection. Once the tooth pulp tissue is fully infected, current treatment options are limited to either removing the diseased pulp and filling the emptied canal with artificial materials such as rubber and cement or extracting the tooth. When a tooth core is filled with artificial inert materials, the pulp-less tooth dries out over time, becomes brittle and more prone to cracking and re-infection. This could eventually lead to extraction of the tooth and replacement with a prosthesis.

The research team led by Dr Waruna Dissanayaka, Assistant Professor in Oral Biosciences, aims to develop an approach to regenerate the lost tooth pulp which could revitalize the tooth and enable it to function like normal tooth.

Stem cell-based therapeutics has been considered a promising strategy in dental pulp regeneration. However, as the tooth root canal is surrounded by hard dental tissue with a limited blood supply, which creates a harsh environment for the cells with low-oxygen and nutrients, low cell viability after transplantation in vivo remains a critical challenge to researchers.

The research team developed a preconditioning protocol that modified the cells genetically to mimic a responsive state for low oxygen conditions in order to activate a protein that induce adaptive changes in the cells.

Dr Yuanyuan Han, a co-investigator of the team pointed out："As this protein was reported to activate several key adaptive mechanisms, we wondered whether this phenomenon can be applied to improve cell survival following transplantation until a sufficient blood supply is achieved."

"In our study, we found that these cells activate a metabolic mechanism to produce energy under low oxygen conditions and scavenge harmful metabolites produced in stress conditions.” Dr Han.  explained.

"Interestingly, we also found that preconditioned cells significantly enhanced the dental hard tissue formation within the regenerated pulp tissue." Dr Dissanayaka stated further.

"Former research has revealed that our cells possess number of adaptive mechanisms for stress, which are regulated by several key genes encoded in our DNA that are normally inactive," Dr Dissanayaka said. "If we can activate these genes, downstream expression of specific proteins can prime the cells less vulnerable to injury."

With the help of Dr Mohamad Koohi-Moghadam, Research Assistant Professor in Clinical Artificial Intelligence, the team investigated which genes are activated or repressed during preconditioning and is further working on to characterize the upregulated downstream proteins that make cells resistant to damage.

"Tooth stem cells have an inherent capacity to survive under stress" Dr Dissanayaka emphasized. "Our aim is to find ways to take advantage of this capacity and use positive stress to help regenerate the dental tissues."

Dr Dissanayaka plans to utilize the knowledge of specific genes and proteins responsible for inducing cell survival to identify drugs that can be used in clinical tissue regeneration. He believes these new findings will promote the development of new strategies to enhance the therapeutic potential of tooth stem cells.

The study won the IADR Colgate Research in Prevention Award at the 2022 IADR General Session. This project was funded by the General Research Fund of the Research Grants Council, Hong Kong.

Journal Article: “HIF-1α Stabilization Boosts Pulp Regeneration by Modulating Cell Metabolism” is published on Journal of Dental Research: HIF-1α Stabilization Boosts Pulp Regeneration by Modulating Cell Metabolism - PubMed (nih.gov)

Dental biorhythm is associated with adolescent weight gain

 

Research led by the University of Kent has discovered evidence of a biorhythm in human primary teeth that is associated with weight gain during adolescence.

 

An international research team led by Dr Patrick Mahoney at Kent’s School of Anthropology and Conservation discovered the biorhythm in primary ‘milk’ molars (Retzius periodicity [RP]) is related to aspects of physical development during early adolescence. A faster dental biorhythm produced smaller gains in weight and mass.

 

RP forms through a circadian-like process, occurring with a repeat interval that can be measured with a resolution of days. The rhythm relates to the period in which tooth enamel forms and is consistent within the permanent molars of individuals that do not retain evidence of developmental stress. The human modal RP has a near seven-day cycle but can vary from five to 12 days.

 

The first-of-its-kind research published by Nature Communications Medicine found that adolescents with a faster biorhythm (five or six-day cycle) weighed less, gained the least weight, and had the smallest change in their body mass index over a 14-month period compared to those with a slower biorhythm. Those with a slow biorhythm (seven or eight-day cycle) produced the greatest weight gain.

 

Dental histologists have known about the biological rhythm for over 100 years, but its significance for body mass and growth emerged recently in studies that compare mammalian species. Research has now focused on the meaning of the rhythm for humans.

 

One surprising finding was that participants with slower biorhythms were six times more likely to have a very high body mass index. Rapid change in body size is a natural consequence of adolescence, but excessive weight gain during puberty can have vast consequences for health such as obesity in adulthood.

 

Dr Mahoney said: ‘This research is an exciting first step. The next step is to determine if the link we have discovered extends to related adverse health outcomes for adults. Potentially, milk teeth may hold a record of this information many years before those outcomes can manifest in adults.’

 

Dr Gina McFarlane, a histologist on the project (also based at Kent), said: ‘Our findings provide a new avenue from which to explore links between overweight children and adult health risks. Milk teeth are naturally exfoliated (drop out) during the childhood years. These discarded teeth contain precise information about a fundamental growth rhythm that we now know tracks adolescent weight gain.’

 

The research paper titled ‘Dental biorhythm associates with adolescent weight gain’ is published by Nature Communications Medicine. doi: 10.1038/s43856-022-00164-x. This research project was funded by the Leverhulme Trust.

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JOURNAL

Communications Medicine

DOI

10.1038/s43856-022-00164-x 

Dentists should give antibiotics to high-risk patients to help prevent life-threatening heart infection

 

●      University of Sheffield study finds that antibiotics reduce the risk of a life-threatening heart infection following invasive dental treatment - for high-risk patients

●      Infective endocarditis (IE) is an infection of the heart valves, that causes heart failure, strokes and other serious disabilities that result in a 30 per cent, first year death rate

●      A causal link between dental treatment and IE has long been suspected with 30 to 40 per cent of cases being caused by bacteria from the mouth, however this link has been questioned due to a lack of robust research. Until now there has also never been a study to demonstrate that antibiotics are effective in reducing the risk of IE

●      Guideline committees around the world, except in the UK, recommend antibiotics are given to people at high-risk of IE before undergoing invasive dental treatment to reduce the risk of developing IE

●      University of Sheffield research is the biggest ever study to examine the link between IE and dental treatment and for the first time confirms that giving antibiotics to those at high IE-risk before invasive dental procedures, significantly reduces the risk of them developing IE

People who are at high risk of developing a life-threatening heart infection should be given antibiotics before undergoing invasive dental procedures, according to new research from the University of Sheffield.

These results suggest that current NICE guidelines, advising against routine use of antibiotics before invasive dental procedures for those at high IE-risk, should be reconsidered.

The study, led by Professor Martin Thornhill from the University’s School of Clinical Dentistry, suggests that current UK guidelines against the use of antibiotics, issued by the National Institute for Health and Care Excellence (NICE), could be putting high-risk patients at unnecessary extra risk when undergoing invasive dental procedures.

At the same time, the results validate guidance in the USA, Europe and elsewhere that recommend that those at high-risk are given antibiotics before invasive dental procedures.

Professor Martin Thornhill, Professor of Translational Research in Dentistry at the University of Sheffield and lead author of the study, said: “Infective endocarditis is a rare but devastating heart infection in which around 30 per cent of people die within the first year of developing it. We know that 30-45 per cent of IE cases are caused by bacteria that derive from the mouth, but what has been unclear and disputed until now is whether there is a strong link between invasive dental procedures, such as tooth extractions, and IE in patients who are at high risk of developing the infection.

“Results from our study validate for the first time the guidance of the major guideline committees around the world, such as The American Heart Association and the European Society for Cardiology, which recommend that those at high IE risk should receive AP before undergoing invasive dental procedures. In contrast, our data suggests that current UK NICE guidance against the routine use of AP, could be putting high risk patients at unnecessary extra risk of developing IE, and should be reviewed in light of this new evidence.”

Published in the Journal of the American College of Cardiology, the research is the biggest ever study to examine the association between infective endocarditis (IE) - a life-threatening infection of the heart often caused by bacteria that derive from the mouth - and invasive dental procedures.

The study was performed in the USA where patients at high IE-risk (those with artificial or repaired heart valves, patients with certain congenital heart conditions or a previous history of IE) are recommended to receive antibiotics before invasive dental procedures - called antibiotic prophylaxis (AP) - to reduce their risk of developing IE.

The research is the first to demonstrate that AP reduces the risk of IE following invasive dental treatment for those at high-risk of developing the infection.

Since the 1950’s, guideline committees around the world have recommended that people at increased risk of IE should be given AP before undergoing invasive dental procedures. However, there has never been any robust research directly linking dental procedures with the development of IE or any study to demonstrate that AP is effective in reducing the risk of developing IE.

Due to this lack of evidence, concerns about the unnecessary use of antibiotics and the risk that AP could promote the development of antibiotic resistant bacteria, guideline committees have since reduced the number of people that AP is recommended for - recommending that only those at high risk for IE should receive AP before invasive dental procedures. In the UK, however, NICE went even further stating that “Antibiotic prophylaxis against infective endocarditis is not recommended routinely for people undergoing dental procedures.”

The study from Sheffield analysed the medical history of nearly eight million people in the USA over a 16 month period, including 36,773 individuals at high-risk of IE. The researchers looked at whether the patients had invasive dental treatment, if they then went on to develop IE within 30 days and whether they had been given AP before the procedure.

Researchers found that 3,774 of those studied developed IE within 30 days of dental treatment. They also found that the risk of developing IE was 160 times greater in those at high IE-risk than in the general low-risk population.

The association between invasive dental procedures an IE was particularly strong for dental extractions and oral surgical procedures. For patients at high IE-risk, the risk of developing IE was one in every 250 extractions and one in every 100 oral surgery procedures without AP cover. The risk in the general low risk population was extremely small.

The study found however, that only 32.6 per cent of high IE-risk patients received AP before invasive dental procedures. This allowed the researchers to study the effectiveness of AP. They found that the risk of developing IE was nearly 10 times greater when dental extractions were performed in high-risk patients without AP cover than when performed with AP cover. Similarly, the risk of IE was 12.5 times greater when oral surgery procedures were performed in high-risk patients without AP cover than when performed with AP cover.

For the USA, even though the study’s results validate The American Heart Association guidance, the research found that compliance with this advice was low –only 32.6 per cent of those at high risk of IE were given AP before undergoing invasive dental procedures.

Professor Thornhill added: “It is reassuring for patients, cardiologists and dentists that our data validates the American, European and other guidelines from around the world that recommend that patients at high risk for IE should receive AP before invasive dental procedures. It is concerning, however, that compliance with this guidance by dentists in the USA was so low. Clearly, more needs to be done to improve compliance with the American Heart Association guidelines.”

The study, Antibiotic Prophylaxis Against Infective Endocarditis Before Invasive Dental Procedures, is published in the Journal of the American College of Cardiology. It was performed in the United States using data from IBM Health and was funded by Delta Dental of Michigan and Renaissance Health Service Corporation in the US. To access the paper, visit: https://doi.org/10.1016/j.jacc.2022.06.030 

Applying microrobotics in endodontic treatment, diagnostics

 

 

IMAGE: MAGNETICALLY ACTUATED 3D MOLDED ROBOTS ARE CONTROLLED PRECISELY TO TARGET THE APICAL REGION OF THE ROOT CANAL UNINTERRUPTED BY THE SURROUNDING PERIODONTIUM AS VISUALIZED AND TRACKED BY CBCT. view more 

CREDIT: PENN DENTAL MEDICINE

With its irregularities and anatomical complexities, the root canal system is one of the most clinically challenging spaces in the oral cavity. As a result, biofilm not fully cleared from the nooks and crannies of the canals remains a leading cause of treatment failure and persistent endodontic infections, and there are limited means to diagnose or assess the efficacy of disinfection. One day, clinicians may have a new tool to overcome these challenges in the form of microrobots.

In a proof-of-concept study, researchers from Penn Dental Medicine and its Center for Innovation & Precision Dentistry (CiPD), have shown that microrobots can access the difficult to reach surfaces of the root canal with controlled precision, treating and disrupting biofilms and even retrieving samples for diagnostics, enabling a more personalized treatment plan. The Penn team shared their findings on the use of two different microrobotic platforms for endodontic therapy in the August issue of the Journal of Dental Research ; the work was selected for the issue’s cover.

“The technology could enable multimodal functionalities to achieve controlled, precision targeting of biofilms in hard-to-reach spaces, obtain microbiological samples, and perform targeted drug delivery, ” says Dr. Alaa Babeer, lead author of the study and a Penn Dental Medicine Doctor of Science in Dentistry (DScD) and endodontics graduate, who is now within the lab of Dr. Michel Koo, co-director of the CiPD .

In both platforms, the building blocks for the microrobots are iron oxide nanoparticles (NPs) that have both catalytic and magnetic activity and have been FDA approved for other uses.  In the first platform, a magnetic field is used to concentrate the NPs in aggregated microswarms and magnetically control them to the apical area of the tooth to disrupt and retrieve biofilms through a catalytic reaction. The second platform uses 3D printing to create miniaturized helix-shaped robots embedded with iron oxide NPs. These helicoids are guided by magnetic fields to move within the root canal, transporting bioactives or drugs that can be released on site.

“This technology offers the potential to advance clinical care on a variety of levels,” says Dr. Koo, co-corresponding author of the study with Dr. Edward Steager, a senior research investigator in Penn’s School of Engineering and Applied Science.

“One important aspect is the ability to have diagnostic as well as therapeutic applications. In the microswarm platform, we can not only remove the biofilm, but also retrieve it, enabling us identify what microorganisms caused the infection. In addition, the ability to conform to the narrow and difficult-to-reach spaces within the root canal allows for a more effective disinfection in comparison to the files and instrumentation techniques presently used.”

A Collaborative System

This microrobotics system is the outgrowth of collaborative work that has been ongoing for several years between Penn Dental Medicine and Penn Engineering. In a recent separate study, Dr. Koo and colleagues constructed the platform to electromagnetically control the microrobots, in that case, enabling microswarms of the iron oxide NPs to adopt different configurations and release antimicrobials on site to effectively treat and remove plaque from teeth.

“We see potential applications of microrobotics systems for both at-home oral care as well as in the dental office for more precise and effective tools for clinicians,” says Dr. Koo.

To determine the effectiveness of the endodontic microrobotic systems to disrupt and retrieve biofilm from the root canal, the researchers conducted experiments in vertically placed 3D printed tooth replicas in collaboration with Dr. Bekir Karabucak, Chair of Penn Dental Medicine’s Department of Endodontics. A mixed-species biofilm containing endodontic bacteria (Streptococcus gordonii, Enterococcus faecalis, Fusobacterium nucleatum, and Actinomyces israelii ) was prepared inside the teeth replicas and the NP suspension was introduced to the root canal. Using electromagnets, microswarms of NPs were created and precisely controlled to disrupt the biofilm. Upon analysis of the collected biofilm, they found all four species were detected, and using a microscope, all nanoparticles appeared to be removed from the root canal.

Breaking the Mold

The second system tested exploits the flexibility of iron oxide NPs as building blocks and involves creating a molded robotic system. Soft corkscrew-like molds in the form of a helicoid (two helices wrapped around a central axis) were 3D printed and filled with a NP-embedded gel. Using a magnetic field, the helicoids were shown to move through the canal with high efficiency to achieve chemical and mechanical disruption of biofilm. Of particular note is the added ability to load the helicoids with therapeutics for targeted drug delivery at the apical region of the root canal where the infection is in close proximity to the surrounding tissues.

In addition, the research team showed the unique ability of track the microrobots in real-time using existing imaging technologies such as intraoral scanner, dental x-ray, and cone-beam computed tomography that were capable of locating the helicoids in the intact tooth canal.

“Importantly, we demonstrated in an ex vivo model that the robots could be controlled by the magnetic field without interruption by the soft and hard tissue surrounding the teeth. In addition, they showed tremendous maneuverability from the top to bottom of the canal,” notes Dr. Karabucak, who explains the magnetic field for both of the endodontic systems tested would be generated by a small device in the oral cavity.

Broad Applications

Along with the potential to enhance endodontic treatment and tissue regeneration, the researchers see this technology as something that could have broad applications across medicine and industry.

“From disinfecting medical devices like catheters to ensuring clean water lines, this technology holds the potential to transform areas far beyond dental medicine,” adds Dr. Koo. “It could disrupt current modalities across disciplines.”

 

Alaa Babeer is a recent graduate of Penn Dental Medicine’s combined Endodontic residency and DScD program.

Michel Koo is a professor in the Department of Orthodontics and divisions of Community Oral Health and Pediatric Dentistry in Penn Dental Medicine and co-director of the Center for Innovation & Precision Dentistry.

Edward Steager is a senior research investigator in Penn’s School of Engineering and Applied Science.

Bekir Karabucak is chair and professor of Endodontics, director of postdoctoral Endodontics program and director of division of Advanced Dental Education at Penn Dental Medicine.

Additional coauthors on the paper are Penn Dental Medicine’s Min Jun Oh, Zhi Ren, Yuan Liu, Fernando Marques and Bekir Karabucak and State University of Rio de Janeiro School of Dentistry’s Ane Poly.

This work was supported in part by the National Institute for Dental and Craniofacial Research (grants R01 DE025848 and R56 DE029985), the National Research Foundation of Korea funded by the Ministry of Education (No. NRF-2021R1A6A3A03044553), Colgate-Palmolive Fellowship, and the NIDCR Postdoctoral Training Program under award number R90DE031532.

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JOURNAL

Journal of Dental Research

DOI

10.1177/00220345221087149

Ditching the toothbrush for whiter teeth, fewer cavities (video)

 

AMERICAN CHEMICAL SOCIETY

 

IMAGE: A NEW HYDROGEL TREATMENT BREAKS APART CAVITY-FORMING BIOFILMS AND WHITENS TEETH WITHOUT DAMAGING ENAMEL. view more 

CREDIT: AMERICAN CHEMICAL SOCIETY

The first thing people notice when they meet you is your smile. To be more confident when giving wide-mouthed, eye-crinkling smiles, people want healthy, pearly white teeth. But toothpastes only remove surface stains, and whitening treatments can harm enamel, leading to cavities and discoloration. Now, researchers in ACS Applied Materials & Interfaces report a new hydrogel treatment that breaks apart cavity-forming biofilms and whitens teeth without damaging them. Watch a video of the treatment here.

Daily toothbrushing and flossing are good ways to prevent cavities from forming, according to the American Dental Association. However, these methods don’t effectively whiten teeth. For better whitening, consumers often turn to over-the-counter or professional treatments that combine hydrogen peroxide-containing gels and blue light, producing a chemical reaction that removes stains. This combination removes most of the discoloration, but generates reactive oxygen species that can break down enamel. Previously, Xiaolei Wang, Lan Liao and colleagues modified titanium dioxide nanoparticles for a less destructive tooth-whitening treatment. This method still required high-intensity blue light, which can damage nearby skin and eyes. So, the team wanted to find a material that would be activated by green light — a safer alternative — to both whiten teeth and prevent cavities.

The researchers combined bismuth oxychloride nanoparticles, copper oxide nanoparticles and sodium alginate into a thick mixture. Then, they evenly coated the mixture onto the surface of teeth stuck to a slide and sprayed the concoction with a calcium chloride solution, forming a strongly adhering hydrogel. Next, the team tested the material on teeth that were stained with coffee, tea, blueberry juice and soy sauce and placed in a lab dish. Following treatment with the hydrogel and green light, the teeth got brighter over time, and there was no damage to the enamel. In another set of experiments, the team showed that the treatment killed 94% of bacteria in biofilms. To demonstrate that the treatment could work on teeth in vivo, the team used the new method on mice whose mouths were inoculated with cavity-forming bacteria. The green-light activated hydrogel effectively prevented moderate and deep cavities from forming on the surface of the animals’ teeth. The researchers say their safe, brush-free treatment both effectively prevents cavities and whitens teeth.

The authors acknowledge funding from the National Natural Science Foundation of China, Key Youth Project of Jiangxi Province, Key Research and Development Program of Jiangxi Province, Natural Science Foundation of Jiangxi Province and the Graduate Innovation Special Fund Project of Jiangxi Province.

For more of the latest research news, register for our upcoming meeting, ACS Fall 2022. Journalists and public information officers are encouraged to apply for complimentary press registration by completing this form.

The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS’ mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world’s scientific knowledge. ACS’ main offices are in Washington, D.C., and Columbus, Ohio.

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JOURNAL

ACS Applied Materials & Interfaces

DOI

10.1021/acsami.2c00887