Jefferson Scientists Design Method to Fight Artificial Implant Infections with Antibiotics
Infections associated with inserting a medical device can be devastating, painful, and cause prolonged disability, costing tens of thousands of dollars.

Now, researchers at Jefferson Medical College have found a way to create a permanent chemical bond between antibiotics and titanium, a material used in orthopedic implants. The proof-of-principle study showed that an antibiotic can be connected to the titanium surface in an active form, and can kill bacteria and prevent infection. The work is a critical first step toward developing stable, bacteria-resistant implants to combat infection.

"The biggest benefit of this work is to keep the infection from ever starting," says Eric Wickstrom, Ph.D., professor of biochemistry and molecular biology at Jefferson Medical College of Thomas Jefferson University, who in collaboration with Noreen Hickok, Ph.D., associate professor of orthopedic surgery at Jefferson Medical College and Allen Zeiger, Ph.D., professor of biochemistry and molecular biology at Jefferson Medical College, developed the bonding method.

Infections associated with orthopedic implants are one of the major causes of implant failure. If bacteria grow on an implant, it can't knit properly with bone. "Our technique puts a bed of antibiotic nails on the surface of the implant," Dr. Wickstrom says. "The first time a bacterium lands on those nails, it dies."

The researchers, along with co-authors Binoy Jose, Ph.D., a former postdoctoral fellow now at SK Biopharmaceuticals, and M.D./Ph.D. student Valentin Antoci, Jr., report their results September 23, 2005 in the journal Chemistry and Biology.

In the work, the scientists fastened the antibiotic vancomycin to titanium powder. The vancomycin could then immediately kill bacteria sensitive to vancomycin that landed on the titanium.

The researchers checked to see if vancomycin was indeed attached to the titanium surface using microscopy. Next, they added a fragment of bacterial cell wall to see if the vancomycin on the powder, or beads, could bind to its natural target. The tests proved that the vancomycin was bound and active.

Finally, they added bacteria and showed that titanium beads with vancomycin on the surface killed the bacteria. When the beads were exposed to more bacteria, the vancomycin continued to kill the new infection. The vancomycin was not only chemically bound, but aggressively curtailed re-infection as well.

The researchers, led by Irving Shapiro, Ph.D., professor of orthopedic surgery at Jefferson Medical College, and including collaborators at the Rothman Institute at Jefferson and the University of Pennsylvania are supported by a grant from the U.S. Department of Defense to develop techniques to protect titanium surfaces with antibiotics.

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