A team of chemical engineers from MIT has developed a new method of stimulating bone growth, by utilizing the same chemical processes that occur naturally in the human body following an injury such as a broken or fractured bone. The technique involves the insertion of a porous scaffold coated with growth factors that prompt the body's own cells to naturally mend the damaged or deformed bone.
Current techniques for replacing or mending damaged bone often include a bone transplant from another area of the patient's body. This is an expensive, painful, and often inadequate option for treatment, as it is difficult to harvest enough bone to successfully treat the wound. Due to the inadequacies of the current forms of bone replacement treatment, a number of scaffold-based approaches are in development, however few are as promising as the tissue scaffold presented by the team from MIT.
The new method would seek to mimic the natural steps taken by the human body to encourage bone growth without the unpleasant necessity of extracting further bone from the patient's body. After a break or fracture, the body releases both platelet-derived growth factors, (PDGF) and bone morphogenetic protein 2 (BMP-2), in order to stimulate natural bone regeneration. These factors essentially recruit other immature cells, coaxing them to become osteoblasts, a cell type with the capacity to create new bone. At the same time, the PDFG and BMP-2 provide a supporting structure around which the bone can be rebuilt.
The 0.1 mm-thick polymer scaffold sheet developed by the scientists from MIT would appear to successfully mimic this biological process, releasing the growth factors in the correct order and quantity, essentially tricking the body into thinking it had initiated the healing process itself. Previous attempts at biomimicry in this area have failed due to an inability to release the growth factors in a natural and controlled fashion, causing the body to clear the factors away from the wound before they could have any substantial healing effect.
"You want the growth factor to be released very slowly and with nanogram or microgram quantities, not milligram quantities," States Paula Hammond, member of MIT's Koch Institute for Integrative Cancer Research and Department of Engineering, and senior author on the paper outlining the results of the study. "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 measured release of growth factors is achieved by layering the porous scaffold with around 40 layers of BMP-2, followed by another 40 layers of PDGF. Once the layering process is complete, medical practitioners can cut out segments of the scaffold, tailoring the treatment to fit any size of wound. Furthermore, once the treatment has run its course and the bone has been regrown, the biodegradable scaffold is safely adsorbed into the body, leaving no harmful traces as a by-product of the procedure.
The scaffold has been tested in the lab by administering the treatment to rats with skull deficiencies too large to be healed without the aid of outside stimuli. It was found that the initial release of the PDGF created a healing cascade, mobilizing cells important to the rebuilding process to move to the site of the deformity. The BMP-2 then went to work inducing a number of the cells to become osteoblasts, which would go on to create the new bone.
Only two weeks after the initial transplant, it was found that fresh bone had been created that was indistinguishable in nature from the natural bone found in the surrounding areas of the skull. Looking to the future, the team hopes to test the technique on larger animals, with the long-term goal of advancing to clinical trials.
A paper covering the research carried out by the team from MIT has been published in the journal Proceedings of the National Academy of Sciences of the United States of America.