Antibiotic-releasing microspheres prevent mesh infection in vivo

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.

Keywords: Antibiotic releasing; Cyclodextrin; Hernia; Infection; Mesh; Microsphere.