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Implant coating emits antibiotics on schedule

An antibiotic-releasing nanofiber coating may prevent serious bacterial infections after knee or hip replacements, a preliminary study suggests.

The study was conducted on mouse knee joints, but the coating—if proven in further research—would have “broad applicability” not only for total joint replacements, but also for implants like pacemakers, stents, and other medical devices, researchers say.

The new material is designed to release multiple antibiotics in a strategically timed way for optimal effect.

“We can potentially coat any metallic implant that we put into patients, from prosthetic joints, rods, screws, and plates to pacemakers, implantable defibrillators, and dental hardware,” says co-senior author Lloyd S. Miller, associate professor of dermatology and orthopedic surgery at Johns Hopkins University School of Medicine.

Surgeons and biomedical engineers have for years looked for better ways—including antibiotic coatings—to reduce infections after artificial hip, knee, and shoulder joint implants.

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Every year, an estimated 1 to 2 percent of the more than 1 million hip and knee replacement surgeries done in the US are followed by infections linked to the formation of biofilms—layers of bacteria that adhere to a surface, forming a dense, impenetrable matrix of proteins, sugars, and DNA.

An acute infection immediately after surgery causes swelling and redness that often can be treated with intravenous antibiotics. But in some people, low-grade chronic infections can last for months, causing bone loss that leads to implant loosening and failure.

These infections are difficult to treat; in many cases, the prosthesis must be removed and the patient placed on a long course of antibiotics before a new one can be implanted. The cost to treat a biofilm-associated prosthesis infection often exceeds $100,000, Miller says.

Existing options for antibiotic delivery with an implant, such as antibiotic-loaded cement, beads, spacers, or powder, typically supply only one antibiotic at a time with a release rate that is not well-controlled. To develop a better approach, Miller teamed up with Hai-Quan Mao, professor of materials science and engineering at Johns Hopkins and a member of its Institute for NanoBioTechnology.

Infection eradicated

For three years, the team worked to design a thin biodegradable plastic coating that could release multiple antibiotics at desired rates. The coating is a nanofiber mesh embedded in a thin film; both components are made of polymers already approved for use in degradable sutures.

To test the technology, described in the Proceedings of the National Academy of Sciences, the researchers loaded the nanofiber coating with the antibiotic rifampin in combination with one of three other antibiotics.

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“Rifampin has excellent anti-biofilm activity but cannot be used alone because bacteria would rapidly develop resistance,” Miller says. The coatings released rifampin over three to five days and the other drugs for seven to 14 days. “We were able to deploy two antibiotics against potential infection while ensuring rifampin was never present as a single agent.”

Glowing bacteria

The team then used each combination to coat titanium Kirschner wires, a type of pin used in orthopedic surgery to fix bone in place after wrist fractures. They inserted the wires into the knee joints of anesthetized mice and introduced Staphylococcus aureus, bacteria that commonly cause biofilm-associated infections in orthopedic surgeries.

The bacteria were engineered to give off light, allowing the researchers to noninvasively track infection over time. After 14 days, mice who received pins without an antibiotic coating had abundant bacteria in infected tissue around the knee joint; 80 percent had bacteria on the surface of the implant. Mice that received coated pins had no detectable bacteria on the implants or in surrounding tissue.

“We were able to completely eradicate infection with this coating,” Miller says. “Most other approaches only decrease the number of bacteria but don’t generally or reliably prevent infections.”

More research is needed to test the coating in humans and sort out which patients would benefit most. Support for the project came from the Johns Hopkins Institute for Clinical and Translational Research, funded by the National Center for Advancing Translational Sciences and the National Institutes of Health Roadmap for Medical Research.

Source: Johns Hopkins University

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