Anodizing the titanium surface of a surgical implant, left, yields a roughened surface of nanotubes., which skin cells colonize more quickly. Credit: Webster Lab/Brown Univ.
In recent years, researchers have worked to develop more flexible,
functional prosthetics for soldiers returning home from battlefields in Afghanistan or Iraq with missing arms or legs. But
even new prosthetics have trouble keeping bacteria from entering the body
through the space where the device has been implanted.
“You need to close (the area) where the bacteria would enter the body, and
that’s where the skin is,” said Thomas Webster, associate professor of
engineering and orthopaedics at Brown
Webster and a team of researchers at Brown may have come across the right
formula to deter bacterial migrants. The group reports two ways in which it
modified the surface of titanium leg implants to promote skin cell growth,
thereby creating a natural skin layer and sealing the gap where the device has
been implanted into the body. The researchers also created a molecular chain to
sprinkle skin-growing proteins on the implant to hasten skin growth.
The findings are published in the Journal
of Biomedical Materials Research A.
The researchers, including Melanie Zile, a Boston Univ. student who worked
in Webster’s lab as part of Brown’s Undergraduate Teaching and Research Awards
program, and Sabrina Puckett, who earned her engineering doctorate last May,
created two different surfaces at the nanoscale, dimensions less than a
billionth of a meter.
In the first approach, the scientists fired an electron beam of titanium
coating at the abutment (the piece of the implant that is inserted into the
bone), creating a landscape of 20-nm mounds. Those mounds imitate the contours
of natural skin and trick skin cells into colonizing the surface and growing
additional keratinocytes, or skin cells.
Webster knew such a surface, roughened at the nanoscale, worked for
regrowing bone cells and cartilage cells, but he was unsure whether it would be
successful at growing skin cells. This may be the first time that a nanosurface
created this way on titanium has been shown to attract skin cells.
Associate Professor of Engineering and Orthopaedics. Credit: Brown Univ.
The second approach, called anodization, involved dipping the abutment into
hydrofluoric acid and giving it a jolt of electric current. This causes the
titanium atoms on the abutment’s surface to scurry about and regather as
hollow, tubular structures rising perpendicularly from the abutment’s surface.
As with the nanomounds, skin cells quickly colonize the nanotubular surface.
In laboratory (in vitro) tests,
the researchers report nearly a doubling of skin cell density on the implant
surface; within five days, the keratinocyte density reached the point at which
an impermeable skin layer bridging the abutment and the body had been created.
“You definitely have a complete layer of skin,” Webster said. “There’s no
more gap for the bacteria to go through.”
To further promote skin cell growth around the implant, Webster’s team
looked to FGF-2, a protein secreted by the skin to help other skin cells grow.
Simply slathering the abutment with the proteins doesn’t work, as FGF-2 loses
its effect when absorbed by the titanium. So the researchers came up with a synthetic
molecular chain to bind FGF-2 to the titanium surface, while maintaining the
protein’s skin-cell growing ability. Not surprisingly, in vitro tests showed the greatest density of skin cells on
abutment surfaces using the nanomodified surfaces and laced with FGF-2.
Moreover, the nanomodified surfaces create more surface area for FGF-2 proteins
than would be available on traditional implants.
The next step is to perform in vivo studies; if they are successful,
human trials could begin, although Webster said that could be years away.