Researchers Develop Nanomodified Surfaces to Seal Prosthetic Implants Against Infection

Despite innumerable technological advances in prosthetics throughout the years, the fact remains that the prosthesis is a foreign body. When the prosthesis is implanted, its alien nature becomes even more evident — due to the open site where the device protrudes from the body — and leaves the patient vulnerable to other foreign substances, like bacteria.

  Thomas J. Webster
  Thomas J. Webster

Thomas J. Webster, PhD, co-director of the Indo-U.S. Center for Biomaterials for Healthcare and associate professor of engineering and orthopedics at Brown University, and a team of researchers at Brown may have come across the right formula to deter that bacteria from entering the body. The group reported two ways in which it modified the surface of titanium leg implants to promote skin cell growth, creating a natural skin layer and sealing the gap where the device was implanted into the body. The researchers also created a molecular chain to sprinkle skin-growing proteins on the implant to hasten skin growth.

These nanostructured formulas keep bacteria from infiltrating the wound by changing the surface energy of the titanium to adsorb proteins that the bacteria do not like — but that skin cells and bone cells do like, Webster told O&P Business News. Researchers mimicked the human body’s natural anti-bacterial proteins and created these nanofeatures on titanium that change the titanium’s surface energy to promote the adsorption of those natural anti-bacterial proteins; similarly, they copied the proteins promoting skin and bone growth that naturally occur in the body to develop nanostructured features that promote the adsorption of those proteins for the same purpose.

“So, we are decreasing implant infection by first keeping bacteria from adhering to the surface and second by quickly closing the wound by promoting skin and bone growth,” he said.

The researchers, whose work was funded by the U.S. Department of Veterans Affairs and the U.S. National Science Foundation, created two different surfaces at the nanoscale, dimensions measuring less than a billionth of a meter.

In the first approach, the scientists fired an electron beam of titanium coating at the abutment, or the piece of the implant that is inserted into the bone, creating a landscape of 20-nanometer mounds. Those mounds imitated the contours of natural skin and tricked skin cells into colonizing the surface and growing additional keratinocytes, or skin cells.

Webster knew that 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, according to a press release. This may be the first time that a nanosurface created this way on titanium has been shown to attract skin cells.

The second approach, called anodization, involved dipping the abutment into hydrofluoric acid and giving it a jolt of electric current. This caused the titanium atoms on the abutment’s surface to scatter and then come together as hollow, tubular structures rising perpendicularly from the abutment’s surface. As with the nanomounds, skin cells quickly colonized the nanotubular surface.

In in vitro tests, the researchers reported a nearly doubling of skin cell density on the implant surface; within 5 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 stated in a press release. “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 did not work, as FGF-2 loses its effect when absorbed by the titanium. Instead, the researchers developed a synthetic molecular chain to bind FGF-2 to the titanium surface, while maintaining the protein’s skin-cell growing ability. In vitro tests showed the greatest density of skin cells on abutment surfaces that used the nanomodified surfaces and were laced with FGF-2. Moreover, the nanomodified surfaces created 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 stated that could be years away.

Although the findings, published in the Journal of Biomedical Materials Research Part A, described procedures specifically for metals like titanium, Webster told O&P Business News that researchers have developed similar procedures for polymers and ceramics.

“So, really, any medical device that suffers from infection or lack of tissue growth can be treated in this way to increase nanoscale surface roughness and promote the lifetime of the device,” he said. “Our focus is to decrease implant infection and promote tissue growth without using drugs, since bacteria are generating a resistance to those drugs. Thus we believe one can modify the implant surface itself to control such biological events that the bacteria will not eventually ‘outsmart’ like they are doing to our pharmaceutical drugs.”

The ultimate result of this technology, Webster said, should be accelerated healing times and decreased rates of infection, which are painful, time consuming and costly.

“We ultimately believe it will decrease the number of complications associated with today’s prosthetics to improve their lifetime and function making for a more comfortable implant,” he said.

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