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In Vivo Efficacy of a “Smart” Antimicrobial Implant Coating

Stavrakis, Alexandra I. MD; Zhu, Suwei PhD; Hegde, Vishal MD; Loftin, Amanda H. BS; Ashbaugh, Alyssa G. BA; Niska, Jared A. MD; Miller, Lloyd S. MD, PhD; Segura, Tatiana PhD; Bernthal, Nicholas M. MD

Journal of Bone & Joint Surgery - American Volume: 20 July 2016 - Volume 98 - Issue 14 - p 1183–1189
doi: 10.2106/JBJS.15.01273
Scientific Articles

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.

1Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California

2Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California

3Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland

E-mail address for N.M. Bernthal: nbernthal@mednet.ucla.edu

* Alexandra I. Stavrakis, MD, and Suwei Zhu, PhD, contributed equally to the writing of this article.

Copyright 2016 by The Journal of Bone and Joint Surgery, Incorporated
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