title: Vancomycin-modified implant surface inhibits biofilm formation and supports bone-healing in an infected osteotomy model in sheep: a proof-of-concept study.
abstract: 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.
authors.affiliation: Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Stewart
authors.forename: Stephanie
authors.initials: S
authors.lastname: Barr
authors.forename: Julie
authors.initials: J
authors.lastname: Engiles
authors.forename: Noreen J
authors.initials: NJ
authors.lastname: Hickok
authors.forename: Irving M
authors.initials: IM
authors.lastname: Shapiro
authors.forename: Dean W
authors.initials: DW
authors.lastname: Richardson
authors.forename: Javad
authors.initials: J
authors.lastname: Parvizi
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Schaer
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects*; D001860:Bone Plates; D020099:Coated Materials, Biocompatible; D004195:Disease Models, Animal; D008855:Microscopy, Electron, Scanning; D010027:Osteotomy; D016459:Prosthesis-Related Infections / Q000517:prevention & control*; D034561:Sheep, Domestic; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013211:Staphylococcus aureus / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects; D013499:Surface Properties; D013977:Tibia / Q000601:surgery*; D014025:Titanium; D014640:Vancomycin / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*; D055114:X-Ray Microtomography
chemical_list: D020099:Coated Materials, Biocompatible; D014640:Vancomycin; D014025:Titanium