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In vivo efficacy of antibiotic-eluting phospholipid coated implants

Abstract

Implant-associated infection can be a serious problem for patients that receive orthopedic implants, such as hip and knee replacements. This is a common cause for early implant loosening, which requires revision surgeries and results in an even greater risk of infection. To address this issue, our lab has developed a novel electrospraying technique for applying phospholipid coatings to orthopedic implants. These coatings consist of two layers of 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS), with antibiotic loaded in between layers. In vitro tests were performed to evaluate how modifications to these coatings affect coating retention, based on a clinically relevant test, and antibiotic elution from these coatings. Coating retention tests were performed by inserting implants through segments of mouse bone and then examining the implants under SEM. Antibiotic elution was performed using a total sink elution combined with OPA assay for detection of antibiotic. These results showed that the coatings that were retained the most and eluted antibiotic slowest were samples that were pre-treated with calcium and were electrosprayed with a mixture of 6:1 DOPS-to-cholesterol. This coating was selected to be used in an in vivo study to determine the efficacy of the coatings in treating osteomyelitis. Osteomyelitis was induced in a murine model using genetically modified bacteria, which allowed tracking of the infection prior to sacrificing the animals via bioluminescent imaging, a technique that makes use of genetically modified bacteria producing luciferin and luciferase which causes emission of photons. It was observed that antibiotic-eluting implants cleared the infection faster than implants without antibiotic during a 4 week study. Also, no kidney damage was observed based on creatinine, blood urea nitrogen, and urine protein tests. Histology confirmed observations from the bioluminescent imaging. These results show that our antibiotic-eluting implant coatings were able to reduce infection in vivo without resulting in adverse effects. Bioluminescent imaging showed significant reduction of emission of photons, p < 0.05, in the antibiotic loaded group compared to the control samples. The results also suggest that the implants exhausted their supply of antibiotic at the end of the study, and in future studies a greater amount of antibiotic will be loaded onto the implants.

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