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Aug 20, 2014

Slow-Release Growth Factors Enhance Bone Repair

Slow-Release Growth Factors Enhance Bone Repair

Scanning electron micrograph of a porous, nanostructured membrane. The membrane has a polyelectrolyte multilayer coating that releases growth factors to promote bone repair. [Nasim Hyder and Nisarg J. Shah]

  • When the body fails to repair bone injuries on its own, a clinician may resort to bone transplantation, which involves implanting bone tissue that has been extracted from another part of the patient’s body, or from a donor. The procedure, however, is fraught with difficulties: risk of disease transmission, short supply, and—last but not least—pain.

    Even worse, the procedure may not work. Some conditions, such as congenital craniomaxillofacial disorders, are particularly difficult to treat.

    Bone repair by means of bioactive materials has been explored as an alternative. Typically, these materials consist of tissue scaffolds that are impregnated with growth factors such as platelet-derived growth factor (PDGF) and bone morphogenetic protein 2 (BMP-2). To date, however, such materials have tended to release their growth factors too quickly. So, instead of inducing tissue repair, the growth factors are rapidly cleared from the treatment site.

    To improve growth factor delivery, researchers at MIT have developed a new approach. They call it layer-by-layer assembly. They start with a very thin, porous scaffold sheet, and then they coat it with layers of PDGF and BMP.

    The MIT researchers, led by Paula Hammond, a member of MIT’s Koch Institute for Integrative Cancer Research and Department of Chemical Engineering, described their layered approach in the Proceedings of the National Academy of Sciences. Their article, entitled “Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction,” appeared online August 18.

    “We report an approach for bone repair using a polyelectrolyte multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair,” wrote the authors. “Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function.”

    Dr. Hammond described the advantages of the layered approach as follows: “You want the growth factor to be released very slowly and with nanogram or microgram quantities, not milligram quantities. 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.”

    The researchers applied a polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. Then they determined that the released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors, the researchers observed, promoted local bone formation that bridged a critical-size defect in the calvaria as early as two weeks after implantation.

    “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,” Dr. Hammond explained.

    In their article, the authors concluded that their approach “could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration.”


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