Novel microcomposite implant for the controlled delivery of antibiotics in the treatment of osteomyelitis following total joint replacement

摘要

The objective of this study was to develop a novel microcomposite implant to be used in the treatment of osteomyelitis following total joint arthroplasty, with the dual purpose of releasing high local concentrations of antibiotic to eradicate the infection while providing adequate mechanical strength to maintain the dynamic or static spacer. Vancomycin-loaded microcomposite implants were fabricated by incorporating drug-loaded microparticles comprised of mesoporous silica into commonly employed polymethylmethacrylate (PMMA) bone cement, to yield a final drug loading of 10% w/w. In vitro release kinetics at 37 degrees C were monitored by reverse-phase high-performance liquid chromatography, and compared to the release kinetics of current therapy implants consisting of drug alone incorporated at 10% w/w directly into PMMA bone cement. Results demonstrated a sevenfold improvement in the elution profile of microcomposite systems over current therapy implants. In vivo delivery of vancomycin to bone from microcomposite implants (70% of payload) was significantly higher than that from current therapy implants (approx. 22% of payload) and maintained significantly higher bone concentrations for up to 2 weeks duration. The elastic modulus showed no statistical difference between microcomposite implants and current standard therapy implants before drug elution, and maintenance of acceptable strength of microcomposite implants postdrug elution. These results demonstrate that we have developed a novel microcomposite spacer that will release continuously high antibiotic concentrations over a prolonged period of time, offering the possibility to eliminate infection and avoid the emergence of new resistant bacterial strains, while maintaining the requisite mechanical properties for proper space maintenance and joint fixation.