Multifunctional 3D-Printed Wound Dressings Containing a Combination of Synergistic Antimicrobials in the Management of MRSA Infected Topical Wounds
Abstract
Despite increased pre- and postoperative care and aseptic practices in surgical rooms, methicillin-resistant Staphylococcus aureus (MRSA) continues to colonize acute surgical wounds. MRSA is also present in chronic nonhealing wounds, such as diabetic foot and pressure ulcers. In this work, advanced antimicrobial-loaded wound dressings are 3D printed using fused deposition modeling. To achieve a high antimicrobial effect, the topical antiseptic octenidine (OCT) was incorporated into the pellets used in the feeder of the extruder prior to fused modeling. Lysostaphin (LYS), a lytic enzyme that cleaves MRSA peptidoglycan, was incorporated by supramolecular interactions on the surface of the OCT-loaded dressings to exploit the anti-MRSA synergy identified here between OCT and LYS showing a fractional inhibition concentration index (FICI) of 0.156. Minimum inhibitory concentration (MIC) and bactericidal concentration (MBC) values for the OCT were 1 and 25 μg/mL, respectively, whereas the MIC and MBC values for the LYS were 0.1 and 0.2 μg/mL, respectively. The resulting dressings completely eradicate MRSA USA 300 inocula (105 CFU/mL) in 96 h. The bactericidal mechanisms exerted by these dressings were identified through molecular techniques, showing lytic effects on the cell wall peptidoglycans of treated bacteria. Additionally, OCT at 1 μg/mL was able to reduce lipopolysaccharide (100 ng/mL)-induced NO production on murine J774A.1 macrophages by more than 90% demonstrating its…
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