title: Antibiotic-releasing microspheres prevent mesh infection in vivo.
abstract: Infection remains a dreaded complication after implantation of surgical prosthetics, particularly after hernia repair with synthetic mesh. We previously demonstrated the ability of a newly developed polymer to provide controlled release of an antibiotic in a linear fashion over 45 d. We subsequently showed that coating mesh with the drug-releasing polymer prevented a Staphylococcus aureus (SA) infection in vivo. To broaden the applicability of this technology, the polymer was synthesized as isolated "microspheres" and loaded with vancomycin (VM) before conducting a noninferiority analysis.
  
  
  
  Seventy-three mice underwent creation of a dorsal subcutaneous pocket that was inoculated with 104colony forming units (CFU) of green fluorescent protein (GFP)-labeled SA (105CFU/mL). Multifilament polyester mesh (7 × 7 mm) was placed into the pocket, and the skin was closed. Mesh was either placed alone (n = 16), coated with VM-loaded polymer (n = 20), placed next to VM-loaded microspheres (n = 20) or unloaded microspheres (n = 10), or flushed with VM solution (n = 7). Quantitative tissue/mesh cultures were performed at 2 and 4 week. Mice with open wounds and explanted mesh were excluded.
  
  
  
  Twenty-two of 23 (96%) tissue-mesh samples from mesh alone or empty miscrospheres were positive for GFP-labeled SA at 2 and 4 wk. Six of seven (86%) samples from the VM flush group were positive for GFP SA at 4 wk. Thirty-eight of 38 (100%) VM-loaded crosslinked cyclodextrin polymers-coated mesh or VM-loaded microspheres were negative for GFP SA at 2 and 4 wk.
  
  
  
  Slow affinity-based drug-releasing polymers in the form of microspheres are able to adequately clear a bacterial burden of SA and prevent mesh infection.
authors.affiliation: Department of General Surgery, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Grafmiller
authors.affiliation: Affinity Therapeutics, Cleveland, Ohio.
authors.forename: Sean T
authors.initials: ST
authors.lastname: Zuckerman
authors.affiliation: Department of General Surgery, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Clayton
authors.initials: C
authors.lastname: Petro
authors.affiliation: Department of General Surgery, University Hospitals Case Medical Center, Cleveland, Ohio.
authors.forename: Lijia
authors.initials: L
authors.lastname: Liu
authors.affiliation: Case Western Reserve University, Department of Biomedical Engineering, Cleveland, Ohio. Electronic address: hav1@case.edu.
authors.forename: Horst A
authors.initials: HA
authors.lastname: von Recum
authors.affiliation: Department of General Surgery, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rosen
authors.affiliation: Affinity Therapeutics, Cleveland, Ohio.
authors.forename: Julius N
authors.initials: JN
authors.lastname: Korley
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D059685:Herniorrhaphy / Q000295:instrumentation*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D016459:Prosthesis-Related Infections / Q000517:prevention & control*; D013203:Staphylococcal Infections / Q000517:prevention & control*; D013526:Surgical Mesh / Q000009:adverse effects*; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D014640:Vancomycin
keywords: Antibiotic releasing; Cyclodextrin; Hernia; Infection; Mesh; Microsphere