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Biomaterial could keep tooth alive after root canal

The researchers are presenting their results today at the 256th National Meeting & Exposition of the American Chemical Society (ACS). "What you end up with after a root canal is a dead tooth," Vivek Kumar, Ph.D., the project's principal investigator, says. "It's no longer responsive. There are no nerve endings or vascular supply. So the tooth is very susceptible to subsequent infection and, ultimately, falling out." During a root canal, the dentist drills off the top of an infected tooth to access the soft tissue inside. The dentist then removes the infected dental pulp and fills the space with tiny rubber rods called gutta percha and caps the repaired tooth with a crown. Kumar and Peter Nguyen, Ph.D., who is presenting the work at the meeting, wanted to develop a material that could be injected in place of the gutta percha. The material would stimulate both angiogenesis, or new blood vessel growth, and dentinogenesis, or proliferation of dental pulp stem cells, within the tooth. Both Kumar and Nguyen are at the New Jersey Institute of Technology. Kumar drew on his previous experience developing a hydrogel that stimulates angiogenesis when injected under the skin of rats and mice. The hydrogel, which is liquid during injection, contains peptides that self-assemble into a gel at the injection site. The peptides contain a snippet of a protein called vascular endothelial growth factor, which stimulates the growth of new blood vessels. Kumar, then a postdoctoral researcher at Rice University, and his coworkers showed that the self-assembling peptide hydrogel stimulated angiogenesis and persisted under the rodents' skin for as long as three months. "We asked the question, if we can stimulate angiogenesis in a limb, can we stimulate angiogenesis in other regions that have low blood flow?" Kumar says. "One of the regions we were really interested in was an organ in and of itself, the tooth." So Kumar and Nguyen added another domain to the self-assembling angiogenic peptide: a piece of a protein that makes dental pulp stem cells proliferate. When the team added the new peptide to cultured dental pulp stem cells, they found that the peptide not only caused the cells to proliferate, but also activated them to deposit calcium phosphate crystals -- the mineral that makes up tooth enamel. However, when injected under the skin of rats, the peptide degraded within one to three weeks. "This was shorter than we expected, so we went back and redesigned the peptide backbone so that we currently have a much more stable version," says Kumar. Now, the team is injecting the peptide hydrogel into the teeth of dogs that have undergone root canals to see if it can stimulate dental pulp regeneration in a living animal. If these studies go well, the researchers plan to move the hydrogel into human clinical studies. They have filed a patent for the redesigned peptide. The hydrogel in its current form likely won't reduce the invasiveness or pain of a root canal, but Kumar and Nguyen are planning future versions of the peptide that contain antimicrobial domains. "Instead of having to rip out everything inside the tooth, the dentist could go in with a smaller drill bit, remove a little bit of the pulp and inject our hydrogel," Kumar says. The antimicrobial portion of the peptide would kill the infection, preserving more of the existing dental pulp, while helping grow new tissue. And the root canal may no longer be such a dreaded procedure. https://www.youtube.com/watch?v=wgJu7ePUGlM Story Source: Materials provided by American Chemical Society. Note: Content may be edited for style and length.

15th September, 2020

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Could the cure for IBD be inside your mouth?

A new collaborative study from the U-M Medical and Dental Schools reveals that inflammatory bowel disease (IBD), which included Crohn's disease and ulcerative colitis and afflicts an estimated 3 million adults in the U.S., may be the latest condition made worse by poor oral health. Nobuhiko Kamada, Ph.D., assistant professor of internal medicine in the division of gastroenterology, has been studying the gut microbiome -- the collection of bacteria that are normally present in the gut -- for years. He noted an emerging link in research literature between an overgrowth of foreign bacterial species in the guts of people with IBD -- bacteria that are normally found in the mouth. "I decided to approach the dental school to ask the question, does oral disease affect the severity of gastrointestinal diseases?" says Kamada. The new mouse study, published in Cell, shows two pathways by which oral bacteria appear to worsen gut inflammation. In the first pathway, periodontitis, the scientific name for gum disease, leads to an imbalance in the normal healthy microbiome found in the mouth, with an increase of bacteria that cause inflammation. These disease-causing bacteria then travel to the gut. However, this alone may not be enough to set off gut inflammation. The team demonstrated that oral bacteria may aggravate gut inflammation by looking at microbiome changes in mice with inflamed colons. "The normal gut microbiome resists colonization by exogenous, or foreign, bacteria," says Kamada. "However, in mice with IBD, the healthy gut bacteria are disrupted, weakening their ability to resist disease-causing bacteria from the mouth." The team found that mice with both oral and gut inflammation had significantly increased weight loss and more disease activity. In the second proposed pathway, periodontitis activates the immune system's T cells in the mouth. These mouth T cells travel to the gut where they, too, exacerbate inflammation. The gut's normal microbiome is held in balance by the action of inflammatory and regulatory T cells that are fine-tuned to tolerate the resident bacteria. But, says Kamada, oral inflammation generates mostly inflammatory T cells that migrate to the gut, where they, removed from their normal environment, end up triggering the gut's immune response, worsening disease. "This exacerbation of gut inflammation driven by oral organisms that migrate to the gut has important ramifications in emphasizing to patients the critical need to promote oral health as a part of total body health and wellbeing," says co-author William Giannobile, DDS, the William K and Mary Anne Najjar professor of dentistry and chair of the department of periodontics and oral medicine at the U-M School of Dentistry. The study has implications for novel treatments for IBD, necessary because "far too many patients still fail medications, leading to reduced quality of life and eventual surgery," says study co-author Shrinivas Bishu, M.D., assistant professor of gastroenterology. "This study importantly implies that clinical outcomes in IBD may be improved by monitoring oral inflammation -- an intriguing concept." Story Source: Materials provided by Michigan Medicine - University of Michigan. Note: Content may be edited for style and length.

16th September, 2020

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Tongue microbes provide window to heart health

"The tongues of patients with chronic heart failure look totally different to those of healthy people," said study author Dr. Tianhui Yuan, No.1 Hospital of Guangzhou University of Chinese Medicine. "Normal tongues are pale red with a pale white coating. Heart failure patients have a redder tongue with a yellow coating and the appearance changes as the disease becomes more advanced." "Our study found that the composition, quantity and dominant bacteria of the tongue coating differ between heart failure patients and healthy people," she said. Previous research has shown that microorganisms in the tongue coating could distinguish patients with pancreatic cancer from healthy people.2 The authors of that study proposed this as an early marker to diagnose pancreatic cancer. And, since certain bacteria are linked with immunity, they suggested that the microbial imbalance could stimulate inflammation and disease. Inflammation and the immune response also play a role in heart failure.3 This study investigated the composition of the tongue microbiome in participants with and without chronic heart failure. The study enrolled 42 patients in hospital with chronic heart failure and 28 healthy controls. None of the participants had oral, tongue or dental diseases, had suffered an upper respiratory tract infection in the past week, had used antibiotics and immunosuppressants in the past week, or were pregnant or lactating. Stainless steel spoons were used to take samples of the tongue coating in the morning, before participants had brushed their teeth or eaten breakfast. A technique called 16S rRNA gene sequencing was used to identify bacteria in the samples. The researchers found that heart failure patients shared the same types of microorganisms in their tongue coating. Healthy people also shared the same microbes. There was no overlap in bacterial content between the two groups. At the genus level, five categories of bacteria distinguished heart failure patients from healthy people with an area under the curve (AUC) of 0.84 (where 1.0 is a 100% accurate prediction and 0.5 is a random finding). In addition, there was a downward trend in levels of Eubacterium and Solobacterium with increasingly advanced heart failure. Dr. Yuan said: "More research is needed, but our results suggest that tongue microbes, which are easy to obtain, could assist with wide-scale screening, diagnosis, and long-term monitoring of heart failure. The underlying mechanisms connecting microorganisms in the tongue coating with heart function deserve further study." Story Source: Materials provided by European Society of Cardiology. Note: Content may be edited for style and length.

16th September, 2020

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Immune-regulating drug improves gum disease

Periodontal disease, also known as gum disease, is a common problem in older adults that causes painful inflammation, bone loss and changes in the good bacteria that live in the mouth. Yet there are no treatments available beyond tooth removal and/or having good oral hygiene. The findings suggest that treatments targeting the aging process in the mouth might help. Rapamycin is an immune-suppressing drug currently used to prevent organ rejection in transplant recipients. Previous studies in mice have also suggested that it may have life-extending effects, which has led to interest in studying the drug's effects in many age-related diseases. "We hypothesised that biological aging contributes to periodontal disease, and that interventions that delay aging should also delay the progress of this disease," says lead author Jonathan An, Acting Assistant Professor at the Department of Oral Health Sciences, University of Washington, Seattle, US. To find out if rapamycin might slow periodontal disease, An and his colleagues added the drug to the food of middle-aged mice for eight weeks and compared their oral health with untreated mice of the same age. Similar to humans, mice also experience bone loss, inflammation and shifts in oral bacteria as they age. Using a 3D-imaging technique called micro-computed tomography, the team measured the periodontal bone, or bone around the tooth, of the rapamycin-treated and untreated mice. They showed that the treated mice had more bone than the untreated mice, and had actually grown new bone during the period they were receiving rapamycin. The work also showed that rapamycin-treated mice had less gum inflammation. Genetic sequencing of the bacteria in their mouths also revealed that the animals had fewer bacteria associated with gum disease and a mix of oral bacteria more similar to that found in healthy young mice. "By targeting this aging process through rapamycin treatment, our work suggests that we can delay the progress of gum disease and actually reverse its clinical features," explains senior author Matt Kaeberlein, Professor of Pathology and Adjunct Professor of Oral Health Sciences at the University of Washington. However, Kaeberlein adds that while rapamycin is already used to treat certain conditions, it can make people more susceptible to infections and may increase their risk of developing diabetes, at least at the higher chronic doses typically taken by organ transplant patients. "Clinical trials in humans are needed to test whether rapamycin's potential oral health and other benefits outweigh its risks," he concludes. Story Source: Materials provided by eLife. Note: Content may be edited for style and length.

16th September, 2020

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Fighting cavities could one day be as easy as taking a pill, research shows

The researchers say the findings could lead to the development of a supplement that patients could take orally to prevent cavities. While developing an effective oral probiotic will require more research, a possible candidate organism has been identified: a previously unidentified strain of Streptococcus, currently called A12. Robert Burne, Ph.D., associate dean for research and chair of the UF College of Dentistry's department of oral biology, and Marcelle Nascimento, D.D.S., Ph.D., an associate professor in the UF College of Dentistry's department of restorative dental sciences, published the findings in late January in the journal Applied and Environmental Microbiology. To maintain a healthy mouth, the oral environment must have a relatively neutral chemical makeup, or a neutral pH. When the environment in the mouth becomes more acidic, dental cavities or other disorders can develop, according to Burne. "At that point, bacteria on the teeth make acid and acid dissolves the teeth. It's straightforward chemistry," Burne said. "We got interested in what activities keep the pH elevated." Previous research by Burne, Nascimento and others found two main compounds that are broken down into ammonia, which helps neutralize acid in the mouth. These compounds are urea, which everyone secretes in the mouth, and arginine, an amino acid. Burne and Nascimento had also previously found that both adults and children with few or no cavities were better at breaking down arginine than people with cavities. Researchers knew bacteria were responsible for breaking down these compounds but needed to investigate which bacteria do this best, and how this inhibits cavities. Part of the answer is A12. "Like a probiotic approach to the gut to promote health, what if a probiotic formulation could be developed from natural beneficial bacteria from humans who had a very high capacity to break down arginine?" said Burne. "You would implant this probiotic in a healthy child or adult who might be at risk for developing cavities. However many times you have to do that -- once in a lifetime or once a week, the idea is that you could prevent a decline in oral health by populating the patient with natural beneficial organisms." A12 has a potent ability to battle a particularly harmful kind of streptococcal bacteria called Streptococcus mutans, which metabolizes sugar into lactic acid, contributing to acidic conditions in the mouth that form cavities. The UF researchers found that A12 not only helps neutralize acid by metabolizing arginine in the mouth, it also often kills Streptococcus mutans. "Also, if A12 doesn't kill Streptococcus mutans, A12 interferes with Streptococcus mutans' ability to carry out its normal processes that it needs to cause disease," Burne said. "If you grow them together, Streptococcus mutans does not grow very well or make biofilms, also known as dental plaque, properly." Nascimento, a clinician, collected plaque samples for the study. Dental plaque is a mass of bacteria that grows on the surface of teeth and can contribute to the formation of cavities. She isolated more than 2,000 bacteria that the researchers then screened to find bacteria that fit the bill. "We then characterized 54 bacteria that metabolized arginine," Nascimento said. "Out of these, A12 stood out for having all of the properties we were looking for in a bacteria strain that could prevent cavities in a probiotic application." The researchers sequenced the entire genome of A12 and plan to turn this discovery into a tool to screen for people who are at a higher risk for developing cavities, in combination with other factors such as a patient's diet and their oral hygiene habits. "We may be able to use this as a risk assessment tool," Nascimento said. "If we get to the point where we can confirm that people who have more of this healthy type of bacteria in the mouth are at lower risk of cavities, compared to those who don't carry the beneficial bacteria and may be at high risk, this could be one of the factors that you measure for cavities risk." Next, the researchers hope to find more instances of A12 in a larger sample of people and to test how prevalent bacteria with similar properties are in the human mouth. Burne and his research team of Nascimento, David Culp, Ph.D., in UF's department of oral biology, and Vincent Richards, Ph.D., an assistant professor at Clemson University, received a five-year, $3 million grant from the National Institutes of Health's National Institute of Dental and Craniofacial Research. The grant, under award R01DE025832, will allow researchers to study the genomics and ecology of A12 and related bacteria in the oral cavity and examine the mechanisms used by beneficial bacteria to promote oral health. Story Source: Materials provided by University of Florida. Original written by Morgan Sherburne. Note: Content may be edited for style and length. Courtesy: Science Direct

8th September, 2020

pic courtesy: daily express
Using physics to improve root canal efficiency

In Physics of Fluids, by AIP Publishing, report calculations with a model of the conical-shaped root canal inside a tooth. This cavity is usually filled with pulp. When the pulp becomes inflamed or infected, an endodontist removes the infected pulp, and then cleans, shapes and fills the canal. The apex is then sealed. A crucial step in this common dental procedure is irrigation, or rinsing, of the root canal cavity with an antibacterial solution, such as sodium hypochlorite. Efficient cleaning and successful destruction of any bacteria or other microbes in the cavity depend on the penetration and cleaning ability of the irrigation fluid. The computational investigation used a structured mesh as a model of the conical root canal cavity. More than 1 million cells in the mesh completely and accurately described both the root canal and the side-vented needle through which the hypochlorite solution is injected. Fluid dynamics equations were used to model flow of the hypochlorite solution. The scientists varied the fluid velocity, temperature and input power to determine the most efficient cleansing technique. As expected, higher fluid velocities lead to better cleansing. Perhaps counterintuitively, cleansing efficiency is higher on the wall behind the needle vent. "The effective area on the root canal wall, in which the shear stress exceeds the critical value to clean the wall, is usually larger behind the needle outlet than in front of it," said author Hanhui Jin. The maximum shear stress also usually occurs on the wall behind the needle outlet, Jin explained. The investigators also looked at the effect of temperature on cleansing. They considered four different temperatures: 22 Celsius, which is room temperature; 37 C, which is body temperature; and two higher temperatures of 45 C and 60 C. Temperatures above 60 C are painful for the patient and tend to cause root canal damage. Increasing the temperature to 45 C, while holding the fluid velocity fixed, improved the depth of cleansing and the cleansing span across the canal's width, but further increases in temperature beyond 45 C actually decreased the cleansing efficiency. The investigators considered the effect of power consumption by the irrigation device. If the power consumption is held at a fixed value, the effect of temperature on cleansing efficiency is much more pronounced. "The fluid circulation within the canal is clearly enlarged when the temperature is increased," said Jin. Therefore, careful control of both power consumption and temperature leads to increased cleaning efficiency. Story Source: Materials provided by American Institute of Physics. Note: Content may be edited for style and length.

15th September, 2020

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