The goal of this proposal is to improve the treatment for infections of artificial hips and knees and other im- planted devices. This multidisciplinary proposal involves established and productive experts in infectious dis- ease, orthopaedic surgery, chemical engineering, fluid dynamics and biomedical engineering from the Dept. of Orthopaedics at the Massachusetts General Hospital (MGH), Harvard Medical School and the School of Engi- neering and Applied Sciences at Harvard University. In this proposal, a new approach that could fundamental- ly change the treatment of device related infections will be evaluated. The long term goal of this work is to de- velop improved methods to reduce the treatment time required for eradicating peri-prosthetic infections. The particular objectives in ths application are to validate a perfusible load bearing 3D printed PEKK polymer for the controlled and sustained local delivery of antibiotics at high peri-implant doses. To achieve this objective, 3D printed polymer rods containing channels for the delivery of fluids will be implanted into the femora of rab- bits that have been inoculated with Staph Aureus. The vancomycin concentration in the medullary canal, joint space and systemic circulation will be determined as well as the presence or absence of infection. Levels of vancomycin will be determined by ELISA based assays. Changes in bone morphology, tissue response and infection status will be determined by radiography, histology and microbiological culture. The central hypothe- sis is that local antibiotic delivery to the peri-implant space can eradicate an established infection in a short pe- riod of time. The rationale for the proposed pilot study is that perfusion enables a broader use of ABx and greatly improved control of local ABx concentrations than ABx elution from PMMA. These advances could re- duce treatment time for TJI from months to weeks. The result of Aim 1 will be a load bearing knee spacer ca- pable of maintaining high levels of vancomycin in the peri-implant space (medullary canal and joint space). The result of Aim 2 will be validation that a femoral rod that can eradicate infection by perfusion of vancomycin. The result of Aim 3 will be validation that a load bearing knee spacer that can eradicate infection by perfusion of vancomycin. The proposed research is innovative because it combines load-bearing implantable materials with the simplicity and flexibility of a perfusible drug delivery system. The proposed research is significant be- cause infection is a burdensome clinical issue that results in prolonged patient suffering, increased mortality and is expected to cost $12 billion USD/yr by 2015. The impact of this study is the potential to rapidly advance treatment for bone and joint infections, reduce healthcare costs and reduce patient suffering.
The proposed research is highly relevant to public health because it proposes an entirely new and efficient means to treat device-related infections. The proposed idea has clinical potential and is relevant to NIH's mission to support innovative discoveries that protect and advance health.
