Sugar-coated
Nanomaterial Excels at Promoting Bone Growth
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 could
translate readily to humans, the researchers say, where an aging but active
population in the U.S. is increasingly receiving this surgery to treat pain due
to disc degeneration, trauma and other back problems. Many other procedures
could benefit from the nanomaterial, ranging from repair of bone trauma to
treatment of bone cancer to bone growth for dental implants.
“Regenerative medicine can improve quality of
life by offering less invasive and more successful approaches to promoting bone
growth,” said Samuel
I. Stupp, who developed the new
nanomaterial. “Our method is very flexible and could be adapted for the
regeneration of other tissues, including muscle, tendons and cartilage.”
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 study, Stupp collaborated with Dr. Wellington K. Hsu,
associate professor of orthopaedic surgery, and Erin L. K. Hsu, research
assistant professor of orthopaedic surgery, both at Northwestern
University Feinberg School of Medicine. 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 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). 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.
The findings were
published today (June 19) in the journal Nature Nanotechnology.
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 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 approach of the Stupp team 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,” said
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.
The Northwestern
research team plans 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 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. 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 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.”
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 provided funding for this
research.
The paper is titled “Sulfated Glycopeptide
Nanostructures for Multipotent Protein Activation.” Stupp and Wellington and Erin Hsu are senior authors
of the paper, and postdoctoral fellows Sungsoo Lee and Timmy Fyrner are first
authors.
MEGAN
FELLMAN
http://www.mccormick.northwestern.edu/news/articles/2017/06/sugar-coated-nanomaterial-excels-at-promoting-bone-growth.html?utm_source=alumni-newsletter-07-01-17&utm_medium=email&utm_campaign=alumni-newsletter&utm_content=email-position2
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