Infections associated with inserting a medical device can bedevastating, painful, and cause prolonged disability, costing tens ofthousands of dollars.
Now, researchers at Jefferson MedicalCollege have found a way to create a permanent chemical bond betweenantibiotics and titanium, a material used in orthopedic implants. Theproof-of-principle study showed that an antibiotic can be connected tothe titanium surface in an active form, and can kill bacteria andprevent infection. The work is a critical first step toward developingstable, bacteria-resistant implants to combat infection.
“Thebiggest benefit of this work is to keep the infection from everstarting,” says Eric Wickstrom, Ph.D., professor of biochemistry andmolecular biology at Jefferson Medical College of Thomas JeffersonUniversity, who in collaboration with Noreen Hickok, Ph.D., associateprofessor of orthopedic surgery at Jefferson Medical College and AllenZeiger, Ph.D., professor of biochemistry and molecular biology atJefferson Medical College, developed the bonding method.
Infectionsassociated with orthopedic implants are one of the major causes ofimplant failure. If bacteria grow on an implant, it can’t knit properlywith bone. “Our technique puts a bed of antibiotic nails on the surfaceof the implant,” Dr. Wickstrom says. “The first time a bacterium landson those nails, it dies.”
The researchers, along with co-authorsBinoy Jose, Ph.D., a former postdoctoral fellow now at SKBiopharmaceuticals, and M.D./Ph.D. student Valentin Antoci, Jr., reporttheir results September 23, 2005 in the journal Chemistry and Biology.
Inthe work, the scientists fastened the antibiotic vancomycin to titaniumpowder. The vancomycin could then immediately kill bacteria sensitiveto vancomycin that landed on the titanium.
The researcherschecked to see if vancomycin was indeed attached to the titaniumsurface using microscopy. Next, they added a fragment of bacterial cellwall to see if the vancomycin on the powder, or beads, could bind toits natural target. The tests proved that the vancomycin was bound andactive.
Finally, they added bacteria and showed that titaniumbeads with vancomycin on the surface killed the bacteria. When thebeads were exposed to more bacteria, the vancomycin continued to killthe new infection. The vancomycin was not only chemically bound, butaggressively curtailed re-infection as well.
The researchers, ledby Irving Shapiro, Ph.D., professor of orthopedic surgery at JeffersonMedical College, and including collaborators at the Rothman Instituteat Jefferson and the University of Pennsylvania are supported by agrant from the U.S. Department of Defense to develop techniques toprotect titanium surfaces with antibiotics.
“The recent resultsare another step toward our ultimate goal of preventing infections inbattlefield fractures and hip and knee implants,” Dr. Shapiro says.
“Thistechnology bonding antibiotics to the implant surface is analogous tohaving land mines,” says orthopedic surgeon Javad Parvizi, M.D., whotreats implant-related infections and works on the project. “Once theorganism steps on the surface, the antibiotic mine explodes and killsthe bacteria. It holds great promise for our patients.”
When ahip or knee implant is infected, physicians give extensive antibiotictreatment and the old implant is replaced. The treatment can includecement-containing antibiotics. “The hope is that the drugs in the gluewill protect the implant, but that doesn’t always work,” Dr. Hickokexplains. She notes that while they are infrequent, such infections canoccur right after surgery from contamination during the operation.Later, infections can start on the implant from a different source inthe body, such as a bladder infection or a dental procedure.
Dr.Wickstrom says the same approach can be used for other antibiotics andother implants. “There are plastic devices – bladder catheters,implants for kidney dialysis, Hickman tubes, pacemakers – every implantyou can think of is a magnet for bacteria,” he says. “The idea ofhaving a permanent chemical bond to the metal is a new approach. Thiscan be used for every metal and plastic implant, with every antibiotic.”
Whilethe current work is proof-of-principle for binding titanium to anantibiotic, the research team has received a new grant for $3 millionfrom the National Institutes of Health for five years to investigateways of encouraging bone growth on implants bearing permanentantibiotics.
“When an infected implant is taken out, it’s usuallycovered with a slimy layer of bacteria,” Dr. Hickok explains. “We’removing from just having a bacteria-killing surface to having one thatprevents infection while promoting better bone-implant interactions.The idea is to have the implant last for many more years and avoidinfection.
“We expect that the ideal chemical bonds will last for years, ideally as long as the implant,” Dr. Hickok says.
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