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    Nanofiber Coating Prevents Infections of Prosthetic Joints

    In a proof-of-concept study with mice, scientists at The Johns Hopkins University have shown that a novel coating they made with antibiotic-releasing nanofibers has the potential to better prevent at least some serious bacterial infections related to total joint replacement surgery.

    A report on the study was published online by Proceedings of the National Academy of Sciences.

    The researchers said the technology would have broad applicability for orthopaedic prostheses, such as hip and knee implants for total joint replacements, as well as for pacemakers, stents, and other implantable medical devices. The new material can release multiple antibiotics in a strategically timed way for an optimal effect, the researchers said, unlike other coatings in development.

    “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,” said co-senior study author Lloyd S. Miller, MD, PhD, an associate professor of dermatology and orthopaedic surgery at the Johns Hopkins University School of Medicine.

    Surgeons and biomedical engineers have for years looked for better ways —including antibiotic coatings — to reduce the risk of infections that are a known complication of implanting artificial hip, knee, and shoulder joints.

    Every year in the US, an estimated 1% to 2% of the more than 1 million hip and knee replacement patients develop a periprosthetic 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.

    These infections can be difficult to treat and, in many cases of chronic infection, the prosthesis is removed and the patient is placed on long courses of antibiotics before a new prosthesis is implanted. The cost per patient often exceeds $100,000 to treat a biofilm-associated infection, Dr. Miller said.

    A major downside to existing options for local antibiotic delivery, such as antibiotic-loaded cement, beads, spacers, or powder, is that they can typically deliver only 1 antibiotic at a time. In addition, the release rate is not well controlled.

    To develop a better approach that addresses those problems, Dr.. Miller teamed up with Hai-Quan Mao, PhD, a professor of materials science and engineering at the Johns Hopkins University Whiting School of Engineering, and a member of the Institute for NanoBioTechnology, Whitaker Biomedical Engineering Institute and Translational Tissue Engineering Center.

    Over the course of 3 years, the team focused on designing a thin, biodegradable plastic coating that could release multiple antibiotics at desired rates. This coating is composed of a nanofiber mesh embedded in a thin film. Both components are made of polymers used for degradable sutures.

    To test the technology’s ability to prevent infection, the researchers loaded the nanofiber coating with the antibiotic rifampin in combination with 1 of 3 other antibiotics: vancomycin, daptomycin, or linezolid. The coatings released vancomycin, daptomycin, or linezolid for 7 to 14 days and rifampin over 3 to 5 days.

    “Rifampin has excellent anti-biofilm activity but cannot be used alone because bacteria would rapidly develop resistance,” Dr. Miller said.

    With the new technology, “We were able to deploy 2 antibiotics against potential infection while ensuring rifampin was never present as a single agent,” he said.

    The team then used each combination to coat titanium Kirschner wires and inserted them into the knee joints of anesthetized mice. They introduced a strain of Staphylococcus aureus that commonly causes biofilm-associated infections in orthopaedic surgeries. The bacteria were engineered to give off light, allowing the researchers to non-invasively track infection over time.

    Dr. Miller said that after 14 days of infection, all mice that received an antibiotic-free coating on the pins had abundant bacteria in the infected tissue around the knee joint; 80% had bacteria on the surface of the implant.

    In contrast, after the same time period, none of the mice that received pins with either linezolid-rifampin or daptomycin-rifampin coating had detectable bacteria on the implants or in the surrounding tissue.

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

    After the 2-week test, the knee joints and adjacent bones were removed for further study. Dr. Miller and Dr. Mao found that not only had infection been prevented, but the bone loss often seen near infected joints — which creates the prosthetic loosening in patients — had also been completely avoided in animals that had received pins with the antibiotic-loaded coating.

    Dr. Miller emphasized that further research is needed to test the efficacy and safety of the coating in humans, and in sorting out which patients would best benefit from the coating — people with a previous prosthesis joint infection receiving a new replacement joint, for example.

    The polymers used to generate the nanofiber coating have already been used in many devices approved by the US Food and Drug Administration, such as degradable sutures, bone plates, and drug delivery systems.