Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Orthop. Aug 18, 2016; 7(8): 467-474
Published online Aug 18, 2016. doi: 10.5312/wjo.v7.i8.467
Antibiotic-loaded phosphatidylcholine inhibits staphylococcal bone infection
Jessica Amber Jennings, Karen E Beenken, Robert A Skinner, Daniel G Meeker, Mark S Smeltzer, Warren O Haggard, Karen S Troxel
Jessica Amber Jennings, Warren O Haggard, Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, United States
Karen E Beenken, Daniel G Meeker, Mark S Smeltzer, Department of Microbiology and Immunology, University of Arkansas Medical Sciences, Little Rock, AR 72205, United States
Robert A Skinner, Jamesport, NY 11947, United States
Karen S Troxel, Zimmer Biomet, Warsaw, IN 46581, United States
Author contributions: Jennings JA planned and performed the majority of experiments and analyzed the data; Beenken KE and Smeltzer MS planned and assisted with animal experiments; Skinner RA and Meeker DG performed surgical procedures; Skinner RA assisted with histological analysis; Haggard WO and Troxel KS assisted with materials formulation and planning experiments.
Supported by Institutional support from Biomet, LLC.
Institutional animal care and use committee statement: Animal studies were approved by the Institutional Review Board at the University of Arkansas for Medical Sciences (IACUC protocol #3540) and followed the IACUC guidelines.
Conflict-of-interest statement: Studies were funded and by Biomet, LLC. Karen S Troxel, PhD, is an employee of Zimmer Biomet.
Data sharing statement: Technical appendix, statistical analysis, and dataset available from the corresponding author at jjnnings@memphis.edu.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jessica Amber Jennings, PhD, Assistant Professor, Department of Biomedical Engineering, University of Memphis, 330 Engineering Technology Building, Memphis, TN 38152, United States. jjnnings@memphis.edu
Telephone: +1-901-6782283 Fax: +1-901-6785281
Received: March 26, 2016
Peer-review started: March 27, 2016
First decision: May 13, 2016
Revised: May 23, 2016
Accepted: June 27, 2016
Article in press: June 29, 2016
Published online: August 18, 2016
Processing time: 144 Days and 14.1 Hours
Abstract

AIM: To test antibiotic-loaded coating for efficacy in reducing bacterial biofilm and development of osteomyelitis in an orthopaedic model of implant infection.

METHODS: Phosphatidylcholine coatings loaded with 25% vancomycin were applied to washed and sterilized titanium wires 20 mm in length. A 10 mm segment was removed from rabbit radius (total = 9; 5 coated, 4 uncoated), and the segment was injected with 1 × 106 colony forming units (CFUs) of Staphylococcus aureus (UAMS-1 strain). Titanium wires were inserted through the intramedullary canal of the removed segment and into the proximal radial segment and the segment was placed back into the defect. After 7 d, limbs were removed, X-rayed, swabbed for tissue contamination. Wires were removed and processed to determine attached CFUs. Tissue was swabbed and streaked on agar plates to determine bacteriological score.

RESULTS: Antibiotic-loaded coatings resulted in significantly reduced biofilm formation (4.7 fold reduction in CFUs; P < 0.001) on titanium wires and reduced bacteriological score in surrounding tissue (4.0 ± 0 for uncoated, 1.25 ± 0.5 for coated; P = 0.01). Swelling and pus formation was evident in uncoated controls at the 7 d time point both visually and radiographically, but not in antibiotic-loaded coatings.

CONCLUSION: Active antibiotic was released from coated implants and significantly reduced signs of osteomyelitic symptoms. Implant coatings were well tolerated in bone. Further studies with additional control groups and longer time periods are warranted. Antibiotic-loaded phosphatidylcholine coatings applied at the point of care could prevent implant-associated infection in orthopaedic defects.

Keywords: Biofilm; Implant; Drug delivery coating; Antibiotic; Orthopaedic infection

Core tip: We report infection preventative results of a novel antibiotic-loaded coating in a severe contaminated model of orthopaedic infection. Phosphatidylcholine coatings loaded with 25% vancomycin, which can be applied to implants immediately prior to implantation, significantly reduced staphylococcal adherence to intramedullary titanium wires in rabbits. Reduction in bacterial load on implants and in tissue for antibiotic-loaded coatings accompanied reduction in swelling and pus formation. Mild inflammatory responses were noted with coated implants compared to uncoated infected controls. This preliminary short term study demonstrates the clinical potential of these broadly applicable coatings and the need for further characterization and development.