Qian Wang at work among plants that host some of the building blocks of his nanomolecular scaffolds.
you break a bone, you know you’ll end up in a cast for weeks. But what
if the time it took to heal a break could be cut in half? Or cut to just
a tenth of the time it takes now? Qian Wang, a chemistry professor at the University of South Carolina, has made tantalizing progress toward that goal.
Wang, Andrew Lee
and co-workers just reported in Molecular Pharmaceutics that surfaces
coated with bionanoparticles could greatly accelerate the early phases
of bone growth. Their coatings, based in part on genetically modified
Tobacco mosaic virus, reduced the amount of time it took to convert stem
cells into bone nodules—from two weeks to just two days.
The key to hastening bone healing or growth is to coax a perfectly natural process to pick up the pace.
you break a rib, or a finger, the healing is automatic,” said Wang.
“You need to get the bones aligned to be sure it works as well as
possible, but then nature takes over.”
is indeed very natural. The human body continuously generates and
circulates cells that are undifferentiated; that is, they can be
converted into the components of a range of tissues, such as skin or
muscle or bone, depending on what the body needs.
conversion of these cells—called stem cells—is set into motion by
external cues. In bone healing, the body senses the break at the
cellular level and begins converting stem cells into new bone cells at
the location of the break, bonding the fracture back into a single unit.
The process is very slow, which is helpful in allowing a fracture to be
properly set, but after that point the wait is at least an
inconvenience, and in some cases highly detrimental.
a broken femur, a leg, you can be really incapacitated for a long
time,” said Wang. “In cases like that, they sometimes inject a
protein-based drug, BMP-2, which is very effective in speeding up the
healing process. Unfortunately, it’s very expensive and can also have
some side effects.”
a search for alternatives four years ago, Wang and colleagues uncovered
some unexpected accelerants of bone growth: plant viruses. They
originally meant for these viruses, which are harmless to humans, to
work as controls. They coated glass surfaces with uniform coverings of
the Turnip yellow mosaic virus and Tobacco mosaic virus, originally
intending to use them as starting points for examining other potential
they were surprised to find that the coatings alone could reduce the
amount of time to grow bone nodules from stem cells. Since then, Wang
and co-workers have refined their approach to better define just what it
is that accelerates bone growth.
the course of the past four years, they’ve demonstrated that it’s a
combination of the chemistry as well as the topography of the surface
that determines how long it takes a stem cell to form bone nodules. The
stem cells are nestled into a nanotopgraphy defined by the plant virus,
and within that nanotopography the cells make contact with the variety
of chemical groups on the viral surface.
and his team are now asserting control over these variables. In the
most recent effort spearheaded by Lee, they built up a layer-by-layer
assembly underneath the virus coating to ensure stability. They also
genetically modified the viral protein to enhance the interaction
between the coating and the stem cells and help drive them toward bone
efforts were rewarded with bone nodules that formed just two days after
the addition of stem cells, compared to two weeks with a standard glass
surface. They’re also carefully following the cellular signs involved
with success. BMP-2 is involved, but as an intrinsic cellular product
rather than an added drug.
Differentiation of stem cells into bone nodules is greatly accelerated by nanomolecular scaffolds developed at the University of South Carolina.
is bone morphogenetic protein 2. It can be added as a protein-based
drug, but it’s a natural protein produced in the cell,” said Wang. “We
see upregulation of the BMP-2 within 8 hours with the new scaffold.”
They also find osteocalcin expression and calcium sequestration, two
processes associated with bone formation, to be much more pronounced
with their new coatings.
we’ve seen could prove very useful, particularly when it comes to
external implants in bones,” said Wang. “With those, you have to add a
foreign material, and knowing that a coating might increase the bone
growth process is clearly beneficial.”
more importantly, we feel we’re making progress in a more general sense
in bone engineering. We’re really showing the direct correlation
between nanotopography and cellular response. If our results can be
further developed, in the future you could use titanium to replace the
bone, and you might be able to use different kinds of nanoscale
patterning on the titanium surface to create all kinds of different
a professor in the department of chemistry and biochemistry at the
University of Oklahoma who was not involved in the work, wrote in an
e-mail that he was “amazed and excited” by the results. “The display of
peptides on viruses, including Tobacco mosaic virus, is a powerful
approach for studying how engineered virus particles can direct stem
discovery that the display of a cell adhesion peptide on Tobacco mosaic
virus can enable the rapid differentiation of stem cells into
bone-forming cells is very important for guiding scientists in designing
a scaffold that can induce rapid bone formation in regenerative
Multivalent Ligand Displayed on Plant Virus Induces Rapid Onset of Bone Differentiation
The promotion of osteoblastic differentiation of rat bone marrow stromal cells by a polyvalent plant mosaic virus