MIT chemical engineers have devised a new implantable tissue scaffold that’s coated with “bone growth factors” that are released slowly over a few weeks. When it’s applied to bone injuries or defects, it helps the body quickly form new bone that looks and acts just like the original. The work is published in a new paper in the Proceedings of the National Academy of Sciences.
This type of “coated scaffold” could offer a dramatic improvement over the current standard for treating bone injuries, according to MIT researchers. The current way to do the procedure is to transplant bone from another part of the patient’s body, which researchers say, is a painful process that does not always supply enough bone.
“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 MIT PhD recipient and lead author of the paper.
MIT researchers tested the scaffold they created on rats with a large skull defect—8 millimeters in diameter—that was not healing 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,” the researchers say in the paper.
BMP, another growth factor, was released more slowly. When both growth factors were used together, according to the report, a layer of bone was generated—just two weeks after surgery—that was indistinguishable from natural bone.
This is how the researchers stimulated 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,” says Paula Hammond, the David H. Koch professor in engineering. “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.
“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, according to researchers, is that the scaffold itself is biodegradable and breaks down inside the body within a few weeks. The scaffold material is a polymer called PLGA, which is widely used in medical treatments and can be manipulated to disintegrate at a specific rate so the researchers can customize it to last only as long as its needed.
What’s next? Hammond’s team has filed a patent and the goal is to start the process in larger animals first, with the hopes of eventually moving it into clinical trials.
Source URL: https://www.bostonmagazine.com/health/2014/08/21/mit-invents-new-treatment-bone-injuries/
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