A new bioactive nanomaterial, powered by sugar, shows promise at stimulating bone regeneration. While the new method has only been studied in an animal model of spinal fusion, researchers at Northwestern University say it could readily translate to humans.
Samuel I. Stupp, professor of materials science and engineering, chemistry, medicine and biomedical engineering at Northwestern University, said:
“Regenerative medicine can improve quality of life by offering less invasive and more successful approaches to promoting bone growth. Our method is very flexible and could be adapted for the regeneration of other tissues, including muscle, tendons, and cartilage.”
In the US, more and more of an aging but active population undergoes spinal fusion to treat pain due to disc degeneration, trauma, and other back problems. Other medical procedures could benefit from the nanomaterial as well, including bone trauma repair, bone cancer treatment, and bone growth for dental implants.
Bone Morphogenetic Protein 2
[caption id=“attachment_91212” align=“alignright” width=“300”] The colored region in a micro-CT image shows regenerated high-quality bone in the spine with minimal use of growth factor.
Credit: Northwestern University[/caption]
The nanomaterial gets its power from sugar molecules. Researchers studied in vivo the effect of the “sugar-coated” nanomaterial on the activity of a clinically used growth factor, called bone morphogenetic protein 2 (BMP-2).
The results show that the amount of protein needed for a successful spinal fusion was reduced to an unprecedented level. 100 times less of BMP-2 was needed — good news, because the growth factor is known to cause dangerous side effects when used in the amounts required to regenerate high-quality bone, and it is expensive as well.
The biodegradable nanomaterial functions as an artificial extracellular matrix, which mimics what cells in the body usually interact with in their surroundings. BMP-2 activates certain types of stem cells and signals them to become bone cells.
The matrix, which consists of tiny nanoscale filaments, binds the protein by molecular design in the way that natural sugars bind it in our bodies and then slowly releases it when needed, instead of in one early burst, which can contribute to side effects.
To create the nanostructures, researchers synthesized a specific type of sugar that closely resembles those used by nature to activate BMP-2 when cell signaling is necessary for bone growth.
Rapidly moving flexible sugar molecules displayed on the surface of the nanostructures “grab” the protein in a specific spot that is precisely the same one used in biological systems when it is time to deploy the signal. This potentiates the bone-growing signals to a surprising level that surpasses even the naturally occurring sugar polymers in our bodies.
In nature, the sugar polymers are known as sulfated polysaccharides, which have super-complex structures impossible to synthesize at the present time with chemical techniques. Hundreds of proteins in biological systems are known to have specific domains to bind these sugar polymers in order to activate signals.
Such proteins include those involved in the growth of blood vessels, cell recruitment, and cell proliferation, all very important biologically in tissue regeneration. Therefore, the new approach could be extended to other regenerative targets.
Spinal fusion is a common surgical procedure that joins adjacent vertebra together using a bone graft and growth factors to promote new bone growth, which stabilizes the spine. The bone used in the graft can come from the patient’s pelvis—an invasive procedure — or from a bone bank.
“There is a real need for a clinically efficacious, safe, and cost-effective way to form bone,” says Wellington Hsu, a spine surgeon. “The success of this nanomaterial makes me excited that every spine surgeon may one day subscribe to this method for bone graft. Right now, if you poll an audience of spine surgeons, you will get 15 to 20 different answers on what they use for bone graft. We need to standardize choice and improve patient outcomes.”
In the in vivo portion of the study, the nanomaterial was delivered to the spine using a collagen sponge. This is the way surgeons currently deliver BMP-2 clinically to promote bone growth.
Researchers next plan to seek approval from the Food and Drug Administration to launch a clinical trial studying the nanomaterial for bone regeneration in humans.
“We surgeons are looking for optimal carriers for growth factors and cells,” Wellington Hsu says. “With its numerous binding sites, the long filaments of this new nanomaterial is more successful than existing carriers in releasing the growth factor when the body is ready. Timing is critical for success in bone regeneration.”
Tissue Regeneration Applications
In the new nanomaterial, the sugars are displayed in a scaffold built from self-assembling molecules known as peptide amphiphiles, first developed by Stupp 15 years ago. These synthetic molecules have been essential in his work on regenerative medicine.
“We focused on bone regeneration to demonstrate the power of the sugar nanostructure to provide a big signaling boost,” Stupp says. “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.”
The study was funded by the National Institute of Dental and Craniofacial Research of the National Institutes of Health and the Louis A. Simpson and Kimberly K. Querrey Center for Regenerative Nanomedicine at Northwestern University.
Sungsoo S. Lee, Timmy Fyrner, Feng Chen, Zaida Álvarez, Eduard Sleep, Danielle S. Chun, Joseph A. Weiner, Ralph W. Cook, Ryan D. Freshman, Michael S. Schallmo, Karina M. Katchko, Andrew D. Schneider, Justin T. Smith, Chawon Yun, Gurmit Singh, Sohaib Z. Hashmi, Mark T. McClendon, Zhilin Yu, Stuart R. Stock, Wellington K. Hsu, Erin L. Hsu & Samuel I. Stupp Sulfated glycopeptide nanostructures for multipotent protein activation Nature Nanotechnology (2017) doi:10.1038/nnano.2017.109
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