Coated tissue scaffolds help the body grow new bone to repair injuries or congenital defects

MIT chemical engineers have devised a new implantable tissue scaffold coated with bone growth factors that are released slowly over a few weeks. When applied to bone injuries or defects, this coated scaffold induces the body to rapidly form new bone that looks and behaves just like the original tissue.

This type of coated scaffold could offer a dramatic improvement over the current standard for treating bone injuries, which involves transplanting bone from another part of the patient’s body – a painful process that does not always supply enough bone. Patients with severe bone injuries, such as soldiers wounded in battle; people who suffer from congenital bone defects, such as craniomaxillofacial disorders; and patients in need of bone augmentation prior to insertion of dental implants could benefit from the new tissue scaffold, the researchers say.

“It’s been a truly challenging medical problem, and we have tried to provide one way to address that problem,” says Nisarg Shah, a recent PhD recipient and lead author of the paper, which appears in theProceedings of the National Academy of Sciencesthis week.

Paula Hammond, the David H. Koch Professor in Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research and Department of Chemical Engineering, is the paper’s senior author. Other authors are postdocs M. Nasim Hyder and Mohiuddin Quadir, graduate student Noémie-Manuelle Dorval Courchesne, Howard Seeherman of Restituo, Myron Nevins of the Harvard School of Dental Medicine, and Myron Spector of Brigham and Women’s Hospital.

Stimulating bone growth

Two of the most important bone growth factors are platelet-derived growth factor (PDGF) and bone morphogenetic protein 2 (BMP-2). As part of the natural wound-healing cascade, PDGF is one of the first factors released immediately following a bone injury, such as a fracture. After PDGF appears, other factors, including BMP-2, help to create the right environment for bone regeneration by recruiting cells that can produce bone and forming a supportive structure, including blood vessels.

Efforts to treat bone injury with these growth factors have been hindered by the inability to effectively deliver them in a controlled manner. When very large quantities of growth factors are delivered too quickly, they are rapidly cleared from the treatment site – so they have reduced impact on tissue repair, and can also induce unwanted side effects.

“You want the growth factor to be released very slowly and with nanogram or microgram quantities, not milligram quantities,” Hammond says. “You want to recruit these native adult stem cells we have in our bone marrow to go to the site of injury and then generate bone around the scaffold, and you want to generate a vascular system to go with it.”

This process takes time, so ideally the growth factors would be released slowly over several days or weeks. To achieve this, the MIT team created a very thin, porous scaffold sheet coated with layers of PDGF and BMP. Using a technique called layer-by-layer assembly, they first coated the sheet with about 40 layers of BMP-2; on top of that are another 40 layers of PDGF. This allowed PDGF to be released more quickly, along with a more sustained BMP-2 release, mimicking aspects of natural healing.

“This is a major advantage for tissue engineering for bones because the release of the signaling proteins has to be slow and it has to be scheduled,” says Nicholas Kotov, a professor of chemical engineering at the University of Michigan who was not part of the research team.

The scaffold sheet is about 0.1 millimeter thick; once the growth-factor coatings are applied, scaffolds can be cut from the sheet on demand, and in the appropriate size for implantation into a bone injury or defect.

Effective repair

The researchers tested the scaffold in rats with a skull defect large enough – 8 millimeters in diameter – that it could not heal on its own. After the scaffold was implanted, growth factors were released at different rates. PDGF, released during the first few days after implantation, helped initiate the wound-healing cascade and mobilize different precursor cells to the site of the wound. These cells are responsible for forming new tissue, including blood vessels, supportive vascular structures, and bone.

BMP, released more slowly, then induced some of these immature cells to become osteoblasts, which produce bone. When both growth factors were used together, these cells generated a layer of bone, as soon as two weeks after surgery, that was indistinguishable from natural bone in its appearance and mechanical properties, the researchers say.

“Using this combination allows us to not only have accelerated proliferation first, but also facilitates laying down some vascular tissue, which provides a route for both the stem cells and the precursor osteoblasts and other players to get in and do their jobs. You end up with a very uniform healed system,” Hammond says.

Another advantage of this approach is that the scaffold is biodegradable and breaks down inside the body within a few weeks. The scaffold material, a polymer called PLGA, is widely used in medical treatment and can be tuned to disintegrate at a specific rate so the researchers can design it to last only as long as needed.

Hammond’s team has filed a patent based on this work and now aims to begin testing the system in larger animals in hopes of eventually moving it into clinical trials.

 

http://www.medicalnewstoday.com/releases/281315.php

 

 

 

What’s the best way to brush teeth? Even dentists and dental associations don’t agree

 

Advice on how we should brush our teeth from dental associations and toothpaste companies is ‘unacceptably inconsistent’, finds new UCL research.

The study, published in the British Dental Journal, looked at the brushing advice given by dental associations across ten countries, toothpaste and toothbrush companies and in dental textbooks. They found a wide range of recommendations on what brushing method to use, how often to brush and for how long.

The researchers found no clear consensus between the various sources, and a ‘worrying’ lack of agreement between advice from dental associations compared with dental textbooks.

“The public needs to have sound information on the best method to brush their teeth,” says Aubrey Sheiham, Emeritus Professor of Dental Public Health (UCL Epidemiology & Public Health), senior author of the study. “If people hear one thing from a dental association, another from a toothbrush company and something else from their dentist, no wonder they are confused about how to brush. In this study we found an unacceptably inconsistent array of advice from different sources.

“Dental associations need to be consistent about what method to recommend, based on how effective the method is. Most worryingly, the methods recommended by dental associations are not the same as the best ones mentioned in dental textbooks. There is no evidence to suggest that complicated techniques are any better than a simple gentle scrub.”

The most commonly-recommended technique involves gently jiggling the brush back and forth in small motions, with the intention of shaking loose any food particles, plaque and bacteria. However, no large-scale studies have ever shown this method to be any more effective than basic scrubbing.

“Brush gently with a simple horizontal scrubbing motion, with the brush at a forty-five degree angle to get to the dental plaque,” Professor Sheiham advises. “To avoid brushing too hard, hold the brush with a pencil grip rather than a fist. This simple method is perfectly effective at keeping your gums healthy.

“There is little point in brushing after eating sweets or sugary drinks to prevent tooth decay. It takes bacteria from food about two minutes to start producing acid, so if you brush your teeth a few minutes after eating sugary foods, the acid will have damaged the enamel.”

The conflicting messages given by different organisations highlight the need for research into how effective different brushing methods are. At present, the expert advice in the guidelines, ‘The scientific basis of dental health education’, recommend a simple scrubbing technique as it is easy to learn and there is no evidence to justify a more complicated method.

“The wide range of recommendations we found is likely due to the lack of strong evidence suggesting that one method is conclusively better than another,” says lead author Dr John Wainwright, who carried out the study at UCL and is now a practising dentist. “I advise my patients to focus their brushing on areas where plaque is most likely to collect – the biting surfaces and where the teeth and gums meet – and to use a gentle scrubbing motion. All too frequently I am asked why the method I am describing differs from how previous dentists have taught them in the past.

“What I feel we need is better research into what the easiest to learn, most effective and safest way to brush is. The current situation where not just individual dentists, but different dental organisations worldwide are all issuing different brushing guidelines isn’t just confusing – it’s undermining faith and trust in the profession as a whole. For something most people do twice a day, you would expect dentists to send a clearer, more unified message to their patients on how to brush their teeth.”

 

http://www.medicalnewstoday.com/releases/280772.php