title: In Vivo Efficacy of a "Smart" Antimicrobial Implant Coating.
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.
  
  
  CONCLUSIONS
  PEG-PPS polymer provides a controlled, "smart" local delivery of antibiotics that could be used to prevent postoperative implant-related infections.
authors.affiliation: Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
authors.forename: Alexandra I
authors.initials: AI
authors.lastname: Stavrakis
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California.
authors.forename: Suwei
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
authors.forename: Vishal
authors.initials: V
authors.lastname: Hegde
authors.affiliation: Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
authors.forename: Amanda H
authors.initials: AH
authors.lastname: Loftin
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Alyssa G
authors.initials: AG
authors.lastname: Ashbaugh
authors.affiliation: Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California.
authors.forename: Jared A
authors.initials: JA
authors.lastname: Niska
authors.affiliation: Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Lloyd S
authors.initials: LS
authors.lastname: Miller
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, California.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Segura
authors.affiliation: Department of Orthopaedic Surgery, Orthopaedic Hospital Research Center, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California nbernthal@mednet.ucla.edu.
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Bernthal
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D051379:Mice; D008911:Minocycline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016459:Prosthesis-Related Infections / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control*; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000517:prevention & control; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D013530:Surgical Wound Infection / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control*; D000078304:Tigecycline; D014640:Vancomycin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D000078304:Tigecycline; D008911:Minocycline