Brussels, 11 Aug 2005
A new method developed by an international team of biomedical engineers has proved for the first time that it is possible to grow healthy new bone in one part of the body and use it to repair damaged bone at a different location. This method has the potential to change approaches to tissue engineering in the future, and is expected to have important applications for engineering other kinds of tissues.
The discovery is reported in a paper published recently by the Proceedings of the National Academy of Sciences.
Living bone is continually growing and reshaping, but attempts to coax bone growth outside of the body - in vitro - have all failed. Recent attempts to stimulate bone growth within the body - in vivo - have had limited success and have proven until now to be extremely complex, expensive and unreliable.
The approach currently used by orthopedic surgeons to repair serious bone breaks is to remove small pieces of bone from a patient's rib or hip and fuse them onto the broken bone. This same method is used to fuse spinal vertebrae to treat serious spinal injuries and back pain. Although it works well at the repair site, the removal operation is extremely painful and can lead to serious complications. The new approach is based on the body's natural wound-healing response. Scientists create a special zone on the surface of a healthy bone in the hope that the body will respond by filling the space with new bone.
Long bones in the body are covered by a thin outer layer called the periosteum. The layer can be compared with scotch tape: the outside is tough and fibrous, but the inside is covered with a layer of special pluripotent cells, capable of transforming into the different types of skeletal tissue.
The team decided to create the bioreactor space just under this outer layer by piercing a tiny hole in the periosteum and injecting saline water underneath. This loosened the layer from the underlying bone and inflated it slightly. When the scientists had created a cavity the size and shape that they wanted, the water was removed and replaced with a commercially available gel for delivery of cells within the human body. This gel contains calcium, a known trigger for bone growth. The scientists' major concern was that the bioreactor would fill with scar tissue instead of bone, but that did not happen. The approach proved correct, and the cavity filled with new bone indistinguishable from the original.
Working with mature rabbits, a species whose bones are very similar to those of humans, the researchers were delighted to find that this zone, which they have dubbed the 'in vivo bioreactor', filled with healthy bone in about six weeks. And there was no need to coax the bone to grow by applying the growth factors required by previous in vivo efforts. They also found that the new bone could be detached easily before it fused with the old bone, leaving the old bone scarred but intact.
If the new method is confirmed, explains V. Prasad Shastri, assistant professor of biomedical engineering at Vanderbilt University, who led the effort, it will be possible to grow new bone for all types of repairs instead of removing it from existing bones. For people with serious bone disease, it may even be possible to grow replacement bone at an early stage and freeze it so that it can be used when it is needed.'
Co-author Molly Stevens, currently a reader at Imperial College in the UK, explains that 'the new bone actually has comparable strength and mechanical properties to native bone and, since the harvested bone is fresh, it integrates really well at a recipient site.'
The next step for the team is to proceed with the large animal studies and clinical trials necessary to determine whether the procedure will work in humans, and then to get it approved for human treatment. Moreover, as the liver and pancreas have outer layers similar to the periosteum, they intend to test the approach with these tissues.
To download the abstract of the Proceedings of the National Academy of Sciences paper, please consult the following web address: http:///www.pnas.org/cgi/content/abstract /102/32/11450
Remarks: Reference document: In vivo engineering of organs: The bone bioreactor. Stevens et al. PNAS.2005; 102: 11450-11455.