Distribution of molecules locally delivered from bone cement

Revision of infected orthopedic implants is successful in most cases when antimicrobials are delivered locally (mixed with bone cement or bone graft which is placed in the site from which the infected tissue was removed); however, there is still a substantial rate of recurrence most likely due to the antimicrobials not achieving a therapeutic dose at all locations in the tissue. To study transport within this environment, gadolinium chelated in diethylene triamine pentaacetic acid (Gd-DTPA), a MRI contrast agent with size and solubility similar to two common antimicrobials (gentamicin and vancomycin), was mixed with bone cement, implanted in vivo into two models of orthopedic surgical wounds, and imaged using MRI 5.5 h after implantation. Image thresholding was used to create two-dimensional and three-dimensional representations of areas/volumes containing detectable concentrations of Gd-DTPA. Distribution is found to be anisotropic with Gd-DTPA transporting preferentially anterior of the implant toward the skin. When fascia is not closed over the implant site, Gd-DTPA transports to the skin and along the subcutaneous plane. The distance transported indicates that transport is likely driven by convection. Finally, the tissue concentration of Gd-DTPA is much less than the concentration loaded into the bone cement.