In vivo efficacy of a “smart” antimicrobial implant coating

AI Stavrakis, S Zhu, V Hegde, AH Loftin, AG Ashbaugh… - JBJS, 2016 - journals.lww.com
AI Stavrakis, S Zhu, V Hegde, AH Loftin, AG Ashbaugh, JA Niska, LS Miller, T Segura
JBJS, 2016journals.lww.com
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 …
Abstract
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× 10 2 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× 10 2, 4.3× 10 3, and 5.9× 10 4 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.
Lippincott Williams & Wilkins