Got a cavity on a tooth? No problem. Just paint on a special peptide solution and the tooth will repair itself. (a peptide is chain of amino acids)
It's a vicious cycle, but one that can be broken, according to researchers at the University of Leeds who have developed a revolutionary new way to treat the first signs of tooth decay. Their solution is to arm dentists with a peptide-based fluid that is literally painted onto the tooth's surface. The peptide technology is based on knowledge of how the tooth forms in the first place and stimulates regeneration of the tooth defect.
It is amazing that the solution to tooth decay can be this simple.
"This may sound too good to be true, but we are essentially helping acid-damaged teeth to regenerate themselves. It is a totally natural non-surgical repair process and is entirely pain-free too," said Professor Jennifer Kirkham, from the University of Leeds Dental Institute, who has led development of the new technique.
The 'magic' fluid was designed by researchers in the University of Leeds' School of Chemistry, led by Dr Amalia Aggeli. It contains a peptide known as P 11-4 that - under certain conditions - will assemble together into fibres. In practice, this means that when applied to the tooth, the fluid seeps into the micro-pores caused by acid attack and then spontaneously forms a gel. This gel then provides a 'scaffold' or framework that attracts calcium and regenerates the tooth's mineral from within, providing a natural and pain-free repair.
On a small group of people the peptide reversed decay from dental caries.
The technique was recently taken out of the laboratory and tested on a small group of adults whose dentist had spotted the initial signs of tooth decay. The results from this small trial have shown that P 11-4 can indeed reverse the damage and regenerate the tooth tissue.
"The results of our tests so far are extremely promising," said Professor Paul Brunton, who is overseeing the patient testing at the University of Leeds Dental Institute. "If these results can be repeated on a larger patient group, then I have no doubt whatsoever that in two to three years time this technique will be available for dentists to use in their daily practice."
Can this peptide be used for tooth rejuvenation? Will it improve worn teeth that have grooves and other signs of wear? It might make sense as a periodic treatment to slow or possibly reverse tooth aging.
While the rabbits are still gloating about gene therapy to prevent clogged rabbit arteries the mice are are cheering development of the capability to grow replacement mouse teeth. Japanese researchers have successfully grown full teeth from stem cells in a mold and then transplanted the teeth into one month old mice. The teeth enabled the mice to chew and eat.
Here is the abstract from the Plos One research report. Note that you can read the full article for free.
Donor organ transplantation is currently an essential therapeutic approach to the replacement of a dysfunctional organ as a result of disease, injury or aging in vivo. Recent progress in the area of regenerative therapy has the potential to lead to bioengineered mature organ replacement in the future. In this proof of concept study, we here report a further development in this regard in which a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone, was successfully transplanted into a properly-sized bony hole in the alveolar bone through bone integration by recipient bone remodeling in a murine transplantation model system. The bioengineered tooth unit restored enough the alveolar bone in a vertical direction into an extensive bone defect of murine lower jaw. Engrafted bioengineered tooth displayed physiological tooth functions such as mastication, periodontal ligament function for bone remodeling and responsiveness to noxious stimulations. This study thus represents a substantial advance and demonstrates the real potential for bioengineered mature organ replacement as a next generation regenerative therapy.
The significance here isn't just in the ability to grow teeth. The jaw responded to the teeth by growing supporting bone and nerves. The bone growth wasn't enough to restore full normal bone support. So there's still a need to develop methods to control bone growth. But the result suggests the potential to achieve full restoration of both bone and teeth after periodontal disease or trauma.
The era of regenerative medicine is drawing near.
Japanese researchers find that a growth factor helps to reverse the effect of periodontitis
In an article titled "FGF-2 Stimulates Periodontal Regeneration: Results of a Multicenter Randomized Clinical Trial," which is published in the International and American Associations for Dental Research's Journal of Dental Research, M. Kitamura, from Osaka University Graduate School of Dentistry, Japan, and a team of researchers conducted a human clinical trial to determine the safety and effectiveness of fibroblast growth factor-2 (FGF-2) for clinical application. This is the largest study to date in the field of periodontal regenerative therapy.
We really ought to have the ability to get receded gums to grow back onto teeth. This is one of many ways where if we could just instruct cells to do our bidding we could prevent or reverse a form of age-related decay in our bodies.
This research looks promising.
A randomized, double-masked, placebo-controlled clinical trial was conducted in 253 adults afflicted with periodontitis. Periodontal surgery was performed, during which one of three different doses of FGF-2 was randomly administered to localized bone defects. Each dose of FGF-2 showed significant superiority over the standard of care (vehicle alone (p < 0.01)) for the percentage of bone fill at 36 wks after administration, and the percentage peaked in the mid-dose FGF-2 group. These results strongly support the topical application of FGF-2 can be efficacious in the regeneration of human periodontal tissue that has been destroyed by periodontitis.
Traditional gum grafting surgery requires surgically excising tissue from the roof of the mouth (the palate) to replace the gum tissue lost around the teeth. Unfortunately, removing tissue from the roof of the mouth extends recovery time and is a major source of patients’ discomfort or pain. According to the American Academy of Periodontology, periodontal disease is the primary cause of tooth loss in adults aged 35 and older. Periodontal disease includes gum recession, also called gingival recession, which can result in tooth root decay and tooth loss.The new tissue regeneration application from Tufts uses platelet concentrate gel applied to a collagen membrane as the graft instead of using tissue from the roof of the mouth. The graft is soaked in the patient’s platelets, using blood drawn in the same visit. Placed over the receding tooth root, the graft is then surgically secured.In order to examine three-year efficacy of the treatment, measurements were taken from six patients in the gum recession area at baseline, 6, and 36 months after surgery. At six months, 24 out of 37 teeth from the six patients had complete root coverage (65 percent). At 36 months, 21 out of 37 teeth from the six patients had complete root coverage (57 percent). The authors said that the recession over three years was minimal and that the results are comparable to traditional gum grafting surgery.
We need methods for engineering tissue to get it to grow where we want and to become the types of tissue we need for repair. Success stories like the one above demonstrate that guided tissue growth isn't only in our distant science fiction future. It is in our short term future as well.
Want to make your teeth last longer? University of Rochester Medical Center researchers find that tooth whitening with hydrogen peroxide does little damage to the teeth as compared to the acidity of orange juice.
Eastman Institute’s YanFang Ren, DDS, PhD, and his team determined that the effects of 6 percent hydrogen peroxide, the common ingredient in professional and over-the-counter whitening products, are insignificant compared to acidic fruit juices. Orange juice markedly decreased hardness and increased roughness of tooth enamel.
Unlike ever before, researchers were able to see extensive surface detail thanks to a new focus-variation vertical scanning microscope. “The acid is so strong that the tooth is literally washed away,” said Ren, whose findings were recently published in Journal of Dentistry. “The orange juice decreased enamel hardness by 84 percent.” No significant change in hardness or surface enamel was found from whitening.
Weakened and eroded enamel may speed up the wear of the tooth and increase the risk for tooth decay to quickly develop and spread. “Most soft drinks, including sodas and fruit juices, are acidic in nature,” Ren said. “Our studies demonstrated that the orange juice, as an example, can potentially cause significant erosion of teeth.”
Your teeth and gums age and wear out just like the rest of your body. Think about what you drink and eat with the idea of slowing your dental aging. I've stopped using my teeth to crack open ice cubes and otherwise have become more conscious of stresses one can inflict on teeth by choice which foods one eats.
"What we're hoping to have happen is to catch [decaying teeth] early and remineralize them," said Sally Marshall, a professor at the University of California at San Francisco. Marshall gave a talk last week at the spring meeting of the Materials Research Society on rebuilding the inner portions of teeth.
While regrowing your uncle's toothless grin from scratch is still a decade away, the ability to use some of the body's own building materials for oral repair would be a boon to dentists, who have been fixing cavities with metal fillings since the 1840s.
Marshall thinks she's just a few years away from knowing how to restore dentin. Give the ability to restore dentin and enamel conventional fillings will become obsolete.
Some skeptics of the prospects for radical life extension see body rejuvenation as a very distant prospect. Yet a method to restore dentin and enamel is a form of rejuvenation. Granted this rejuvenation is only done to teeth. But teeth are a part of the body. So rejuvenation therapy to one part of the body is just a few years away.
Dental enamel is the hardest tissue produced by the body. It cannot regenerate itself, because it is formed by a layer of cells that is lost by the time the tooth appears in the mouth. The enamel spends the remainder of its lifetime vulnerable to wear, damage, and decay. For this reason, it is exciting to consider the prospect of artificially growing enamel, or even whole teeth, using culturing and transplantation techniques.
Consider how people wear braces to straighten teeth. Also, people get replacement crowns put on teeth. But instead of replacement crowns imagine braces that hold a covering over teeth and that inside the covering cells get inserted that can grow enamel. You'd wear enamel growing incubators over your teeth to build them back up after years of wear and tear. The existing teeth would get recapped periodically using the same types of cells that created the teeth in the first place.
Some Japanese scientists have made progress on methods to grow enamel-forming cells in larger numbers.
In the emergent field of tooth-tissue engineering, several groups have developed their own approaches. Although there has been some success in producing enamel-like and tooth-like tissues, problems remain to be solved before the technology comes close to being tested in humans. One of the issues has been how to produce, in culture, sufficient numbers of enamel-forming cells.
Today, during the 85thth General Session of the International Association for Dental Research, a team of researchers from the Institute of Medical Science, the University of Tokyo (Japan), reports on a new technique for culturing cells that have the capacity to produce enamel.
The scientists boosted cell growth by use of a special feeder cell layer. My guess: some day synthetic surfaces and drugs that serve in their place.
This group has recently shown that epithelial cells extracted from the developing teeth of 6-month-old pigs continue to proliferate when they are cultured on top of a special feeder layer of cells (the feeder-layer cells are known as the 3T3-J2 cell line). This crucial step boosts the number of dental epithelial cells available for enamel production. In the study being reported today, the researchers seeded the cultured dental epithelial cells onto collagen sponge scaffolds, along with cells from the middle of the tooth (dental mesenchymal cells). The scaffolds were then transferred into the abdominal cavities of rats, where conditions were favorable for the cells in the scaffolds to interact and develop. When removed after 4 weeks, the remnants of the scaffolds were found to contain enamel-like tissue. The key finding of this study was that even after the multiple divisions that occurred during propagation of the cells in culture, the dental epithelial cells retained the ability to produce enamel, as long as they were later provided with an appropriate environment.
Useful human treatments still lie years in the future. But these results provide hope for better dental repair solutions 10 to 15 years from now.
I expect the rate of increase in this research to accelerate as microfluidic devices, gene chips, nanomaterials, and other tools for working at small scales provide scientists with much faster and easier ways to manipulate and measure cells and cellular components.
Los Angeles, CA., Dec.20, 2006-A multi-national research team headed by USC School of Dentistry researcher Songtao Shi, DDS, PhD, has successfully regenerated tooth root and supporting periodontal ligaments to restore tooth function in an animal model. The breakthrough holds significant promise for clinical application in human patients.
The study appears December 20 in the inaugural issue of PLoS ONE.
Utilizing stem cells harvested from the extracted wisdom teeth of 18- to 20-year olds, Shi and colleagues have created sufficient root and ligament structure to support a crown restoration in their animal model. The resulting tooth restoration closely resembled the original tooth in function and strength.
Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla). Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs) to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance.
The researchers used swine (i.e. pigs) to grow the teeth in.
To accomplish functional tooth regeneration, we used swine because of the similarities in swine and human orofacial tissue organization. Swine SCAP were loaded into a root-shaped HA/TCP block that contained an inner post channel space to allow the subsequent installation of a porcelain crown (Figure 5A). A lower incisor was extracted and the extraction socket was further cleaned with a surgical bur to remove remaining periodontal tissues (Figure 5A). The HA/TCP block containing SCAP was coated with Gelfoam (Pharmacia Canada Inc., Ontario, Canada) containing PDLSCs and inserted into the socket and sutured for 3 months (Figure 5B–E). CT examination revealed a HA/SCAP-Gelfoam/PDLSC structure growing inside the socket with mineralized root-like tissue formation and periodontal ligament space. The surface of the implanted HA/SCAP-Gelfoam/PDLSC structure was surgically re-opened at three months post-implantation, and a pre-fabricated porcelain crown resembling a minipig incisor was inserted and cemented into the pre-formed post channel inside the HA/TCP block (Figure 5F–H). After suture of the surgical opening, the porcelain crown was retained in situ and subjected to the process of tooth function for four weeks (Figure 5I, J). CT and histologic analysis confirmed that the root/periodontal structure had regenerated (Figure 5K–M). Moreover, newly formed bio-roots demonstrated a significantly improved compressive strength than that of original HA/TCP carriers after six-month implantation (Figure 5N). These findings suggest the feasibility of using a combination of autologous SCAP/PDLSCs in conjunction with artificial dental crowns for functional tooth regeneration.
We need the ability to grow replacement parts. Every step in that direction is something to be cheered. Way to go scientists!
Hockey players, rejoice! A team of University of Alberta researchers has created technology to regrow teeth--the first time scientists have been able to reform human dental tissue.
Using low-intensity pulsed ultrasound (LIPUS), Dr. Tarak El-Bialy from the Faculty of Medicine and Dentistry and Dr. Jie Chen and Dr. Ying Tsui from the Faculty of Engineering have created a miniaturized system-on-a-chip that offers a non-invasive and novel way to stimulate jaw growth and dental tissue healing.
"It's very exciting because we have shown the results and actually have something you can touch and feel that will impact the health of people in Canada and throughout the world," said Chen, who works out of the Department of Electrical and Computer Engineering and the National Institute for Nanotechnology.
The wireless design of the ultrasound transducer means the miniscule device will be able to fit comfortably inside a patient's mouth while packed in biocompatible materials. The unit will be easily mounted on an orthodontic or "braces" bracket or even a plastic removable crown. The team also designed an energy sensor that will ensure the LIPUS power is reaching the target area of the teeth roots within the bone. TEC Edmonton, the U of A's exclusive tech transfer service provider, filed the first patent recently in the U.S. Currently, the research team is finishing the system-on-a-chip and hopes to complete the miniaturized device by next year.
"If the root is broken, it can now be fixed," said El-Bialy. "And because we can regrow the teeth root, a patient could have his own tooth rather than foreign objects in his mouth."
The device is aimed at those experiencing dental root resorption, a common effect of mechanical or chemical injury to dental tissue caused by diseases and endocrine disturbances. Mechanical injury from wearing orthodontic braces causes progressive root resorption, limiting the duration that braces can be worn. This new device will work to counteract the destructive resorptive process while allowing for the continued wearing of corrective braces. With approximately five million people in North America presently wearing orthodontic braces, the market size for the device would be 1.4 million users.
This would allow more rapid realignment of teeth for those undergoing orthodontic therapy.
El-Bialy had previously demonstrated this effect using a larger ultrasound generator. He teamed up with other faculty and developed a wearable device so that the benefit could be had more easily. His previous research showed that the ultrasound also helped cause damaged bones to repair.
El-Bialy has shown in earlier research that ultrasound waves, the high frequency sound waves normally used for diagnostic imaging, help bones heal and tooth material grow.
"I was using ultrasound to stimulate bone formation after lower-jaw lengthening in rabbits," El-Bialy said in an interview Tuesday.
To his surprise, not only did he help heal the rabbits' jaws after the surgery, but their teeth started to grow as well.
He foresees the day when people with broken bones will wear ultrasound emittters wrapped into the bandages.
This approach by itself probably can't solve the problem of growing replacements for entirely missing teeth. However, ultrasound might help stimulate tooth building cells once scientists develop techniques for creating suitable cells. Still, additional problems must be solved to get tooth building cells to produce the particular tooth shape desired.
ANN ARBOR, Mich.---A University of Michigan research team has found that introducing a growth factor protein into a mouth wound using gene therapy helped generate bone around dental implants, according to a new paper in the February issue of the journal Molecular Therapy.
In a patient with a sizeable mouth wound, replacing a tooth takes more than simply implanting a new one---the patient also needs the bone structure to anchor the new tooth in place. Such reconstructive surgery today involves either taking a bone graft from the patient's chin or jaw, which leaves a second wound needing to heal, or using donated bone from a tissue bank, which yields unpredictable results.
William Giannobile, professor of periodontics, prevention and geriatrics, led a team at the U-M School of Dentistry that delivered the gene encoding for bone morphogenetic protein-7 (BMP-7) to large bone defects in rats in an attempt to turn on the body's own bone growth mechanisms. The study showed that animals that got the BMP-7 treatment produced nearly 50 percent more supporting bone around dental implants than those receiving the conventional treatment.
"This study represents a proof-of-concept investigation. We are encouraged about the promise of this treatment," said Giannobile, also an associate professor of biomedical engineering and director of the Michigan Center for Oral Health Research.
More work will need to be done before the approach can be tested in humans, Giannobile added. He said he optimistically would like to see initial trials begin in humans in four to seven years.
One can imagine gene therapy of this sort being used in conjunction with cell therapies being developed to grow new teeth.
A class of composite materials helps in the repair of natural teeth.
"Smart materials" invented at the National Institute of Standards and Technology (NIST) soon may be available that stimulate repair of defective teeth. Laboratory studies show that these composites, made of amorphous (loosely structured) calcium phosphate embedded in polymers, can promote re-growth of natural tooth structures efficiently. In the presence of saliva-like solutions, the material releases calcium and phosphate ions, forming a crystalline calcium phosphate similar to the mineral found naturally in teeth and bone. Developed through a long-standing partnership between NIST and the American Dental Association (ADA), these bioactive, biocompatible materials are described in a forthcoming paper in the NIST Journal of Research.
Plans are being made for clinical trials, and several companies have expressed interest in licensing the patented material once a production-ready form is available. Initial applications include adhesive cements that minimize the decay that often occurs under orthodontic braces. The material also can be used as an anti-cavity liner underneath conventional fillings and possibly in root canal therapy.
NIST and ADA scientists continue to enhance the material's physicochemical and mechanical properties and remineralizing behavior, thereby extending its dental and even orthopedic applications. For example, the researchers found that adding silica and zirconia to the material during processing stabilizes the amorphous calcium phosphate against premature internal formation of crystals, thereby achieving sustained release of calcium and phosphate over a longer period of time.
What would be handy would be a way to use this material to cause a gradual repair of cracks and pits and small chipped off areas.
We are getting close to the era of replacement body parts:
U.S. doctors said Thursday they have managed to grow living pig teeth in rats, a feat of biotechnology that experts said could spark a dental revolution.
10 years till we can get new teeth:
The researchers said they hope that within five years they will have developed techniques to grow teeth of a specific size and shape, and that within 10 years it will be possible to regenerate human teeth.
Update: Science Daily has a more detailed report. Note that the estimate here is for 10 to 15 years with more qualifiers:
The Forsyth results, demonstrated in some two dozen experiments, represent the first successful generation of mature tooth crowns containing both dentin and enamel. The results also suggest that it may be possible to grow teeth of a particular size and shape, according to Pamela C. Yelick, PhD, the principal investigator, an Assistant Member of the Staff at Forsyth.
Previous researchers had used alternative approaches to form partial tooth structures including dentin and pulp, but none had grown complete structures that included enamel.
The Forsyth team is the first to report using dissociated tooth tissues (tooth buds enzymatically digested into single cells) combined with polymer scaffolding (a technique used elsewhere to regrow other bodily human tissues) to regenerate teeth.
Also of great importance is the discovery that dental stem cells appear to exist in porcine third molar tissues. "Finding putative epithelial and mesenchymal dental stem cell populations in mammals suggests that similar cells might exist in human beings," Yelick said.
Yelick predicts that within five years, "we will know whether dental stem cells can be manipulated to bioengineer teeth. To generate a human tooth might take an additional five to ten years."
Update: More details on how it was done:
The Forsyth researchers adapted techniques developed by Joseph Vacanti, MD, director of the Laboratory for Tissue Engineering and Organ Fabrication at Massachusetts General Hospital. Dr. Vacanti has used these techniques to successfully regenerate neonatal intestines, which are derived from specialized epithelial and mesenchymal cells. Likewise, teeth are derived from specialized dental epithelial and mesenchymal cells (see glossary, below).
The Yelick team began by isolating porcine tooth buds. They minced the buds into small clusters of cells, then used enzymes to dissociate the clusters into single cells.
The researchers used these cells to seed biodegradable polymer scaffolds at a sufficient density to support tissue growth, then implanted the scaffolding near the intestines of rats. The main purpose of the scaffolding, made of a polymer material, was to serve as a supporting matrix for the forming tissue.Next Steps
Within 20-to-30 weeks, small (2x2x2 millimeter) tooth crowns containing both dentin (a bone-like material found under the enamel) and enamel had formed.
The researchers’ finding of putative (assumed) dental stem cell populations in mammals suggests that similar cells might exist in humans, but scientists do not yet know the exact location of such cells. In the near future, the Forsyth researchers plan further study on how the regenerated teeth grow, how they interact with the scaffolding, and how best to grow teeth of a specific size and shape.
The researchers believe that within five years, they will have developed the techniques needed to grow such teeth and that within ten years, human tooth regeneration may be possible. DIAGRAM:
A diagram of the tooth formation process is available on the World Wide Web at http://bite-it.helsinki.fi/