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Vancomycin-Modified Implant Surface Inhibits Biofilm Formation and Supports Bone-Healing in an Infected Osteotomy Model in Sheep: A Proof-of-Concept Study

Stewart, Suzanne MVB; Barr, Stephanie BS; Engiles, Julie VMD; Hickok, Noreen J. PhD; Shapiro, Irving M. BDS, PhD; Richardson, Dean W. DVM; Parvizi, Javad MD; Schaer, Thomas P. VMD

Journal of Bone & Joint Surgery - American Volume: 1 August 2012 - Volume 94 - Issue 15 - p 1406–1415
doi: 10.2106/JBJS.K.00886
Scientific Articles
Supplementary Content

Background: Implant-associated infections contribute to patient morbidity and health care costs. We hypothesized that surface modification of titanium fracture hardware with vancomycin would support bone-healing and prevent bacterial colonization of the implant in a large-animal model.

Methods: A unilateral transverse mid-diaphyseal tibial osteotomy was performed and repaired with a titanium locking compression plate in nine sheep. Four control animals were treated with an unmodified plate and five experimental animals were treated with a vancomycin-modified plate. The osteotomy was inoculated with 2.5 × 106 colony-forming units of Staphylococcus aureus. The animals were killed at three months postoperatively, and implants were retrieved aseptically. Microbiologic and histologic analyses, scanning electron and confocal microscopy, and microcomputed tomography were performed.

Results: All animals completed the study. Compared with the treatment cohort, control animals exhibited protracted lameness in the operatively treated leg. Gross findings during necropsy were consistent with an infected osteotomy accompanied by a florid and lytic callus. Microcomputed tomography and histologic analysis of the tibiae further supported the presence of septic osteomyelitis in the control cohort. Thick biofilms were also evident, and bacterial cultures were positive for Staphylococcus aureus in three of four control animals. In contrast, animals treated with vancomycin-treated plates exhibited a healed osteotomy site with homogenous remodeling, there was no evidence of biofilm formation on the retrieved plate, and bacterial cultures from only one of five animals were positive for Staphylococcus aureus.

Conclusions: Vancomycin-derivatized plate surfaces inhibited implant colonization with Staphylococcus aureus and supported bone-healing in an infected large-animal model.

Clinical Relevance: Binding of vancomycin to the surface of implants holds great promise in helping to reduce protracted and recalcitrant implant-associated infections in orthopaedic patients.

1Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, 382 West Street Road, Kennett Square, PA 19348. E-mail address for T.P. Schaer: tpschaer@vet.upenn.edu

2Department of Orthopaedic Surgery, Thomas Jefferson University, 1015 Walnut Street, Curtis Building, Suite 501, Philadelphia, PA 19107

3Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 382 West Street Road, Kennett Square, PA 19348

4The Rothman Institute, 925 Chestnut Street, Philadelphia, PA 19107

Copyright 2012 by The Journal of Bone and Joint Surgery, Incorporated
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