Abstract
Introduction
Radiation cross-linking of ultrahigh molecular weight polyethylene (UHMWPE) has reduced the in vivo wear and osteolysis associated with bearing surface wear (1), significantly reducing revisions associated with this complication (2). Currently, one of the major and most morbid complications of joint arthroplasty is peri-prosthetic infection (3). In this presentation, we will present the guiding principles in using the UHMWPE bearing surface as a delivery device for therapeutic agents and specifically antibiotics. We will also demonstrate efficacy in a clinically relevant intra-articular model.
Materials and Methods
Medical grade UHMWPE was molded together with vancomycin at 2, 4, 6, 8, 10 and 14 wt%. Tensile mechanical testing and impact testing were performed to determine the effect of drug content on mechanical properties. Elution of the drug was performed in phosphate buffered saline (PBS) for up to 8 weeks and the detection of the drug in PBS was done by UV-Vis spectroscopy. A combination of vancomycin and rifampin in UHMWPE was developed to address chronic infection and layered construct containing 1 mm-thick drug-containing UHMWPE in the non-load bearing regions was developed for delivery. In a lapine (rabbit) intra-articular model (n=6 each), two plug of the layered UHMWPE construct were placed in the trochlear grove of the rabbit femoral surface and a porous titanium rod with a pre-grown biofilm of bioluminescent S. Aureus was implanted in the tibia. Bioluminescent imaging was employed to visualize and quantify the presence of the bacteria up to 3 weeks.
Results and Discussion
Increasing drug content decreased both the ultimate tensile strength (UTS) and the impact toughness of vancomycin-containing UHMWPE (Figure 1). Elution data and structural analysis suggested that a percolation threshold was reached at above 6 wt% drug in UHMWPE, which resulted in sustained drug delivery above the minimum inhibitory concentration (MIC; 1 mg/ml) for up to 8 weeks (Figure 2). The layered constructs implanted in rabbits were able to eradicate all detectable bacteria from the biofilm on the titanium surfaces implanted on the counterface (Figure 3), suggesting clinically relevant efficacy.
Significance
To our knowledge, this is the first study showing the design and efficacy of an antibiotic-eluting UHMWPE bearing surface. Such a device has the potential of reducing all two-stage revisions to single-stage treatment with load-bearing components, enhancing the mobility and quality of life for the patients and reducing the cost of infection treatment in arthroplasty.
For figures/tables, please contact authors directly.
