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Periprosthetic infection is a devastating consequence of implant insertion and can arise from hematogenous sources or surgical contamination. Microbes can preferentially colonize the implant surface and, by forming a biofilm, escape immune surveillance. We hypothesized that if an antibiotic can be tethered to a titanium alloy (Ti) surface, it will inhibit bacterial colonization, prevent biofilm formation, and avert late-stage infection. To test this hypothesis, a Ti rod was covalently derivatized with vancomycin. Reaction efficiencies were evaluated by colorimetric and spectrophotometric measurements. The vancomycin-modified surface was stable in aqueous solutions over extended time periods and maintained antibiotic coverage, even after press-fit insertion into a cadaverous rat femora. When evaluated using fluorescently labeled bacteria, or by direct colony counts, the surface-bound antibiotic prevented bacterial colonization in vitro after: (1) exposure to high levels of S. aureus; (2) extended incubation in physiological buffers; and (3) repeated bacterial challenges. Importantly, whereas the vancomycin-derivitized pins prevented bacterial colonization, S. aureus adhered to control pins, even in the presence of concentrations of vancomycin that exceeded the strain MIC. These results demonstrate that we have effectively engineered a stable, bactericidal Ti surface. This new surface holds great promise in terms of mitigating or preventing periprosthetic infection. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:858–866, 2007

Self-protecting Ti6Al4V alloy pins were prepared by covalent bonding of bis(ethylene glycol) linkers, then vancomycin to the oxidized, aminopropylated Ti6Al4V alloy surface. Fluorescence modification-enabled estimation of yields of free amines on the metallic surface monolayer at each reaction step. The vancomycin-protected Ti6Al4V pins were not colonized by Staphylococcus aureus , even after 44 days storage in physiological buffer. These results provide a basis for testing self-protection against S. aureus colonization in animal models.