Kevin T Grafmiller1, Sean T Zuckerman2, Clayton Petro1, Lijia Liu1, Horst A von Recum3, Michael J Rosen4, Julius N Korley2. 1. Department of General Surgery, University Hospitals Case Medical Center, Cleveland, Ohio. 2. Affinity Therapeutics, Cleveland, Ohio. 3. Case Western Reserve University, Department of Biomedical Engineering, Cleveland, Ohio. Electronic address: hav1@case.edu. 4. Department of General Surgery, Cleveland Clinic, Cleveland, Ohio.
Abstract
BACKGROUND: 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. MATERIALS AND METHODS: Seventy-three mice underwent creation of a dorsal subcutaneous pocket that was inoculated with 104 colony forming units (CFU) of green fluorescent protein (GFP)-labeled SA (105 CFU/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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. MATERIALS AND METHODS: Seventy-three mice underwent creation of a dorsal subcutaneous pocket that was inoculated with 104 colony forming units (CFU) of green fluorescent protein (GFP)-labeled SA (105 CFU/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. RESULTS: 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. CONCLUSIONS: 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.
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