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Spinal fusion and...sugar?
EVANSTON, Ill.—Sugar plays a variety of roles in the human body, but it's not one that usually comes to mind for growth or construction. However, thanks in part to a synthesized version of natural sugars, a new nanomaterial has been developed that could offer a safer, less expensive option for bone regeneration.
Northwestern University researchers have created a bioactive, biodegradable nanomaterial capable of significantly stimulating bone regeneration. It was developed by Samuel I. Stupp, director of Northwestern’s Simpson Querrey Institute for BioNanotechnology and the Board of Trustees Professor of Materials Science and Engineering, Chemistry, Medicine and Biomedical Engineering, who collaborated with Dr. Wellington K. Hsu, associate professor of orthopedic surgery, and Erin L. K. Hsu, research assistant professor of orthopedic surgery, both at Northwestern University Feinberg School of Medicine.
The paper, titled “Sulfated Glycopeptide Nanostructures for Multipotent Protein Activation,” was published June 19 in Nature Nanotechnology.
The nanomaterial was tested in vivo in animal models of spinal fusion, delivered to the spine via a collagen sponge. This is the current method for delivering a clinically used growth factor known as bone morphogenetic protein 2 (BMP-2) in order to stimulate bone growth. With this new material, Stupp and his team found that 100 times less BMP-2 was needed for a successful spinal fusion. Given that BMP-2 is known to come with dangerous side effects when administered in sufficient amounts for regenerating high-quality bone, this is an encouraging result.
Spinal fusion surgery consists of fusing vertebrae together using a bone graft—either from the patient's pelvis or from a bone bank—and growth factors, such that the vertebrae heal into one unit. It is used to address issues such as degenerative disc disease, scoliosis, fracture, infection or tumors, among others.
Essentially, BMP-2 activates certain stem cells and signals them to turn into bone cells. For its part, this new nanomaterial works as an artificial extracellular matrix, mimicking what cells usually interact with in their surroundings. It is comprised of tiny nanoscale filaments that bind BMP-2 by molecular design, in the same way that standard sugars bind it in the human body and releases it gradually when needed.
As for the sugar used in the new nanomaterial, the team synthesized a type of sugar similar to those naturally used to activate BMP-2. Quick, flexible sugar molecules on the surface of the nanostructures latch onto the protein in the spot used by biological systems, triggering the bone-regeneration signals to a degree that surpasses those engendered by the natural sugars. The sugars coating this nanomaterial are held in a scaffold comprised of self-assembling molecules known as peptide amphiphiles, which Stupp developed 15 years ago.
The natural sugar polymers mimicked by those of the nanomaterial are known as sulfated polysaccharides. These polymers feature highly complex structures that are beyond the ability of current chemical techniques to synthesize. Hundreds of proteins in various biological systems are known to have domains to bind these sugar polymers in order to activate signals—such as those playing roles in angiogenesis, cell recruitment and cell proliferation—meaning that this new approach could demonstrate utility for other targets as well.
“Regenerative medicine can improve quality of life by offering less-invasive and more successful approaches to promoting bone growth,” said Stupp. “Our method is very flexible and could be adapted for the regeneration of other tissues, including muscle, tendons and cartilage.”
Moving forward, the scientists intend to reach out to the U.S. Food and Drug Administration for approval to begin a clinical trial studying this new technology's utility for bone regeneration in humans.
“We focused on bone regeneration to demonstrate the power of the sugar nanostructure to provide a big signaling boost,” Stupp said. “With small design changes, the method could be used with other growth factors for the regeneration of all kinds of tissues. One day we may be able to fully do away with the use of growth factors made by recombinant biotechnology and instead empower the natural ones in our bodies.”
SOURCE: Northwestern University press release by Megan Fellman