Method offers pathway for improving patient outcomes after spinal fusion surgery.
There hasn’t been a gold standard for how orthopaedic spine surgeons promote new bone growth in patients, but now Northwestern University scientists have designed a bioactive nanomaterial that is so good at stimulating bone regeneration it could become the method surgeons prefer.

While studied in an animal model of spinal fusion, the method for promoting new bone growth, published in the journal Nature Nanotechnology, could translate readily to humans, the scientists said.

Many other procedures could also benefit from the nanomaterial, ranging from repair of bone trauma to treatment of bone cancer to bone growth for dental implants.

Samuel Stupp, PhD, director of the Louis A. Simpson and Kimberly K. Querrey Institute for BioNanotechnology in Medicine and professor of Medicine in the Division of Endocrinology, Metabolism, and Molecular Medicine, who developed the new nanomaterial, explained: “Our method is very flexible and could be adapted for the regeneration of other tissues, including muscle, tendons and cartilage.”

For the interdisciplinary study, Stupp collaborated with Wellington Hsu, MD, the Clifford C. Raisbeck, MD, Professor of Orthopaedic Surgery and of Neurological Surgery, and Erin Hsu, PhD, research assistant professor of Orthopaedic Surgery. The husband–and–wife team is working to improve clinically employed methods of bone regeneration.

Sugar molecules on the surface of the nanomaterial provide its regenerative power. The investigators 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). They found the amount of protein needed for a successful spinal fusion was reduced to an unprecedented level: 100 times less of BMP–2 was needed. This is very 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.

Stupp’s 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 Northwestern 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, the research team led by Stupp 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 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.

“We surgeons are looking for optimal carriers for growth factors and cells,” 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 displayed in a scaffold built from self–assembling molecules known as peptide amphiphiles, first developed by Stupp 15 years ago.