Posted in | Nanomedicine

Sugar-Coated Nanomaterial Boosts Bone Growth

Until now there is no gold standard for the way in which orthopedic spine surgeons stimulate new bone growth in patients. Recently, Researchers from Northwestern University have designed a bioactive nanomaterial that is very good at stimulating bone regeneration and it could become the process surgeons may favor in the future.

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The new method for promoting new bone growth has been studied in an animal model of spinal fusion. The team believes that the method could translate readily to humans, where an aging but active population in the U.S. is gradually receiving this surgery to treat pain caused by trauma, disc degeneration and other back problems.

A number of other procedures could profit from the nanomaterial, ranging from repair of bone trauma and bone growth for dental implants to treatment of bone cancer.

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.

Samuel I. Stupp, Developer of the new nanomaterial

Stupp is 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.

For the interdisciplinary research, Stupp partnered 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 husband and wife team aims to enhance clinically employed techniques of bone regeneration.

Sugar molecules located on the surface of the nanomaterial give its regenerative power. The Researchers examined in vivo the effect of the “sugar-coated” nanomaterial on the activity of a clinically used growth factor, referred to as bone morphogenetic protein 2 (BMP-2). They found the quantity of protein required for an effective spinal fusion was decreased to an unmatched level: 100 times less of BMP-2 was required. This is excellent news, because the growth factor is recognized to cause risky side effects when used in the quantities required to regenerate high-quality bone. Plus it is expensive.

Their findings have been published in the June 19th issue of the journal Nature Nanotechnology.

Stupp’s biodegradable nanomaterial works as an artificial extracellular matrix, which imitates what cells in the body typically interact with in their surroundings. BMP-2 triggers certain types of stem cells and signals them to change into bone cells. The Northwestern matrix, which comprises of miniature nanoscale filaments, binds the protein by molecular design in the way that natural sugars bind it in human bodies and then gradually discharges it when required, instead of in one single early burst, which can lead to side effects.

To develop the nanostructures, the research team guided by Stupp synthesized a specific type of sugar that closely resembles those used by nature to trigger BMP-2 when cell signaling is needed for bone growth. Swiftly moving flexible sugar molecules showed on the surface of the nanostructures “grab” the protein in a particular spot that is exactly the same one used in biological systems when it is time to deploy the signal. This potentiates the bone-growing signals to an unexpected level that exceeds even the naturally occurring sugar polymers in human bodies.

In nature, the sugar polymers are called sulfated polysaccharides, which have super-complex structures difficult to synthesize currently with chemical methods. Numerous proteins in biological systems are said to have specific domains to bind these sugar polymers so as to trigger signals. Such proteins include those that are needed in the growth of blood vessels, cell proliferation and cell recruitment, all very significant biologically in tissue regeneration. Thus, the method of the Stupp team could be stretched to cover other regenerative targets.

Spinal fusion is a standard surgical procedure that combines adjacent vertebra together using a bone graft and growth factors to boost new bone growth, which stabilizes the spine. The bone used in the graft can be taken from the patient’s pelvis — an invasive technique — or from a bone bank.

There is a real need for a clinically efficacious, safe and cost-effective way to form bone. 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.

Dr. Wellington K. Hsu, Associate Professor of Orthopedic Surgery and Spine Surgeon

In the in vivo phase of the research, the nanomaterial was supplied to the spine using a collagen sponge. This is the method currently used by Surgeons to deliver BMP-2 clinically to boost bone growth.

The Northwestern research team will be seeking approval from the Food and Drug Administration to introduce a clinical trial analyzing the nanomaterial for bone regeneration in humans.

We surgeons are looking for optimal carriers for growth factors and cells,” Wellington Hsu said. “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.”

In the new nanomaterial, the sugars are revealed in a scaffold constructed from self-assembling molecules known as peptide amphiphiles, first developed by Stupp more than a decade ago. These artificial molecules have been vital 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. 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.

Samuel I. Stupp, Developer of the new nanomaterial

This research was funded by the National Institute of Dental and Craniofacial Research of the National Institutes of Health (grant 5R01DE015920-10) and the Louis A. Simpson and Kimberly K. Querrey Center for Regenerative Nanomedicine at Northwestern University.

The research paper is titled “Sulfated Glycopeptide Nanostructures for Multipotent Protein Activation.” Stupp and Wellington and Erin Hsu are the paper’s Senior Authors, and Postdoctoral Fellows Sungsoo Lee and Timmy Fyrner are First Authors.

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