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Tiny "nanotubes" that assemble themselves using
the same chemistry as DNA could be ideal for creating better artificial
joints and other body implants.
Researchers at Purdue University, the University of Alberta and
Canada's National Institute for Nanotechnology have discovered that
bone cells called osteoblasts attach better to nanotube-coated titanium
than they do to conventional titanium used to make artificial joints.
"We have demonstrated the same improved bone-cell adhesion with other
materials, but these nanotubes are especially promising for biomedical
applications because we'll probably be able to tailor them for specific
parts of the body," said Thomas Webster, an assistant professor of
biomedical engineering at Purdue.
Findings are detailed in a paper appearing in the April issue of
Nanotechnology, published by the Institute of Physics in the United
Kingdom. The paper was written by Purdue biomedical engineering
doctoral student Ai Lin Chun, Purdue chemistry doctoral student Jesus
G. Moralez, Webster and Hicham Fenniri, a professor of chemistry at the
University of Alberta and senior research officer at the Canadian
nanotechnology institute, where Chun and Moralez are doctoral students
as well.
The self-assembling nanotubes were developed by Fenniri while he was an
assistant professor at Purdue.
Webster has shown in a series of experiments that bone cells and cells
from other parts of the body attach better to various materials that
possess surface bumps about as wide as 100 nanometers, or billionths of
a meter.
Conventional titanium used in artificial joints has surface features on
the scale of microns, or millionths of a meter, causing the body to
recognize them as foreign and prompting a rejection response. The
body's rejection response eventually weakens the attachment of the
implants and causes them to become loose and painful, requiring
replacement surgery.
The nanometer-scale bumps mimic surface features of proteins and
natural tissues, not only prompting cells to stick better but promoting
the growth of new cells. Bone and other tissues adhere to artificial
body parts by growing new cells that attach to the implants, so the
experiments offer hope in developing longer lasting and more natural
implants, Webster said.
Now researchers have discovered that the self-assembling nanotubes
represent an entirely new and potentially superior material to use for
artificial body parts.
Fenniri created the self-assembling structures by using the chemistry
of deoxyribonucleic acid, or DNA, to make a series of molecules that
are "programmed" to link in groups of six to form tiny rosette-shaped
rings. Numerous rings then combine to create the rod-like nanotubes,
which have widths of only about 3.5 nanometers.
"He had these nice nanotubes, and I had this work that showed nice bone
synthesis and other tissue regeneration on nanomaterials, so we said,
'Wouldn't it be great to actually combine the two to see if his
material can promote new bone growth with these nanotubes?'" Webster
said.
One nanometer is roughly the length of 10 hydrogen atoms strung
together. A human hair is more than 30,000 times wider than the rosette
nanotubes used in the study.
Self-assembly is a well-known principle in biology in which the right
mix of molecules interact on their own to form distinctive structures
ranging from DNA to cells and organs. The rosette-shaped rings are made
of guanine and cytosine, which are molecules called "base pairs" that
come together to form DNA.
In addition to possible biomedical applications, the nanotubes offer
promise in the design of future materials, electronic devices and drug
delivery systems.
The researchers coated titanium with the nanotubes and placed them in
Petri plates containing a liquid suspension of bone cells colored with
a fluorescent dye. After a few hours, the nanotube-coated titanium was
washed, and a microscope was used to count how many of the dyed
osteoblasts adhered to the material. Out of 2,500 bone cells in the
suspension, 2,300 to 2,400 were found to adhere to the nanotube-coated
metal. That compares with about 1,500 cells adhering to titanium not
coated with the nanotubes, representing an increase of about one-third.
The quick attachment of bone cells is critical to create a solid bond
between orthopedic implants and the body's natural bone. The same
applies to artificial parts transplanted in other parts of the body,
such as arteries and the brain.
"The reason we are so excited is that we see improved osteoblast
function on the coated titanium compared to the plain titanium,"
Webster said.
Webster has found similar results with other materials that possess the
nano-scale surface bumps, such as ceramics, metals and nanotubes made
of carbon. The rosette nanotubes, however, may provide a major
advantage over those materials, he said.
Protein components, such as "signaling peptides," or amino acids, such
as lysine and arginine, can be easily attached to the surface of the
nanotubes, making it feasible to tailor the nanotubes so that they are
recognized by specific cells and body parts.
"There are definite amino acid sequences that bone cells recognize and
stick to," Webster said. "One of those sequences is arginine, glycine
and aspartic acid. There is a lot of work in the field now to
incorporate this sequence into materials.
"One of the other reasons we were so excited about this is that we can
put this sequence on these tubes."
Attaching the sequence of amino acids onto the nanotubes will likely
increase osteoblast adhesion even more, Webster said.
Various parts of the body recognize and attach to different sequences.
"I think this really points to strong biomedical applications," Webster
said. "If the cells you are targeting respond to protein sequence XYZ,
you just put that sequence on the nanotubes and you can promote this
attachment."
Another finding in the research is that low concentrations of the
nanotubes provide the same results as higher concentrations.
"That means you can use very low concentrations of this and still get
statistically higher bone-cell attachment," Webster said. "So it's
cheap. You don't need a lot of it to get the effect that you want."
Unlike other nano-scale materials Webster has worked with, the rosette
nanotubes automatically arrange themselves into a webbed pattern on the
surface of the titanium. The pattern resembles those seen by natural
collagen fibers in bones and other tissues.
Future work will focus on further modifying the nanotubes and
conducting additional experiments.
The need for better technology is growing as more artificial body parts
are used, Webster said.
For example, about 152,000 hip replacement surgeries were performed in
the United States in 2000, representing a 33 percent increase from
1990. The number of hip replacements by 2030 is expected to grow to
272,000 in this country alone because of aging baby boomers.
The research has been funded by the National Science Foundation,
American Chemical Society, Purdue Research Foundation, Whitaker
Foundation, 3M Co. and Canada's National Institute for Nanotechology.
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