Background: Postoperative infection is a devastating complication following arthroplasty. The goals of this study were to introduce a “smart” implant coating that combines passive elution of antibiotic with an active-release mechanism that “targets” bacteria, and to use an established in vivo mouse model of post-arthroplasty infection to longitudinally evaluate the efficacy of this polymer implant coating in decreasing bacterial burden.
Methods: A novel, biodegradable coating using branched poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS) polymer was designed to deliver antibiotics both passively and actively. In vitro-release kinetics were studied using high-performance liquid chromatography (HPLC) quantification in conditions representing both the physiologic environment and the more oxidative, hyperinflammatory environment of periprosthetic infection. The in vivo efficacy of the PEG-PPS coating delivering vancomycin and tigecycline was tested using an established mouse model of post-arthroplasty infection. Noninvasive bioluminescence imaging was used to quantify the bacterial burden; radiography, to assess osseointegration and bone resorption; and implant sonication, for colony counts.
Results: In vitro-release kinetics confirmed passive elution above the minimum inhibitory concentration (MIC). A rapid release of antibiotic was noted when challenged with an oxidative environment (p < 0.05), confirming a “smart” active-release mechanism. The PEG-PPS coating with tigecycline significantly lowered the infection burden on all days, whereas PEG-PPS-vancomycin decreased infection on postoperative day (POD) 1, 3, 5, and 7 (p < 0.05). A mean of 0, 9, and 2.6 × 102 colony-forming units (CFUs) grew on culture from the implants treated with tigecycline, vancomycin, and PEG-PPS alone, respectively, and a mean of 1.2 × 102, 4.3 × 103, and 5.9 × 104 CFUs, respectively, on culture of the surrounding tissue (p < 0.05).
Conclusions: The PEG-PPS coating provides a promising approach to preventing periprosthetic infection. This polymer is novel in that it combines both passive and active antibiotic-release mechanisms. The tigecycline-based coating outperformed the vancomycin-based coating in this study.
Clinical Relevance: PEG-PPS polymer provides a controlled, “smart” local delivery of antibiotics that could be used to prevent postoperative implant-related infections.
Investigation performed at the University of California, Los Angeles, Los Angeles, California
Disclosure: This research was supported by the NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number KL2TR000122 (N.M.B.), the Orthopaedic Research and Education Foundation (OREF) Young Investigator Award (N.M.B.), the AO Foundation Start-up Grant Program (L.S.M. and J.A.N.), and an H & H Lee Surgical Resident Research Scholars Program Grant (A.I.S.). On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a patent and/or copyright, planned, pending, or issued, broadly relevant to this work.
- Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated
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