162752 20251017144621.0 doi 10.1021/acsami.5c08968 sideral 145322 ART-2025-145322 eng Mattar, Iman Multifunctional 3D-Printed Wound Dressings Containing a Combination of Synergistic Antimicrobials in the Management of MRSA Infected Topical Wounds 2025 Access copy available to the general public Unrestricted 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 simultaneous anti-inflammatory action. This effect was also corroborated by the qRT-PCR analysis of several pro-inflammatory genes including IL-1β, IL-6, TNF-α, and Nos2. The combination of OCT and LYS within the dressings reveals higher in vivo therapeutic effects compared to free compounds or individual antimicrobial-loaded dressings. In vitro and in preclinical models, the use of OCT-LYS dressings effectively reduces MRSA bioburden and inflammation, promoting fast wound healing. info:eu-repo/grantAgreement/ES/AEI/CEX2023-001286-S info:eu-repo/grantAgreement/ES/ISCIII/FORT23-00028 info:eu-repo/grantAgreement/ES/ISCIII/MS19-00092 info:eu-repo/grantAgreement/ES/MICINN/PID2020-113987RB-I00 info:eu-repo/grantAgreement/ES/MICINN/PID2023-146091OB-I00 info:eu-repo/grantAgreement/ES/MICINN PRE2022-105709 info:eu-repo/grantAgreement/ES/UZ/LMA-ELECMI ICTS info:eu-repo/semantics/openAccess by https://creativecommons.org/licenses/by/4.0/deed.es info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Landa, Guillermo Universidad de Zaragoza (orcid)0000-0003-1599-8216 Frutos-Lizano, Marina Izquierdo, Natalia Tapia, Elena Universidad de Zaragoza Perez, Marta Universidad de Zaragoza (orcid)0000-0002-8133-2124 Lujan, Lluis Universidad de Zaragoza (orcid)0000-0002-2053-9842 Irusta, Silvia (orcid)0000-0002-2966-9088 Mendoza, Gracia (orcid)0000-0003-2293-363X Arruebo, Manuel Universidad de Zaragoza (orcid)0000-0003-3165-0156 1001 025 Universidad de Zaragoza Dpto. Anatom.,Embri.Genét.Ani. Área Anatom.Anatom.Patológ.Com 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 5005 555 Universidad de Zaragoza Dpto. Ing.Quím.Tecnol.Med.Amb. Área Ingeniería Química 0 X Universidad de Zaragoza S. Gral. Apoyo Investig. - SAI Servicios. División Biomédica 17, 34 (2025), 47951-47968 ACS appl. mater. interfaces ACS applied materials & interfaces 1944-8244 11245007 http://zaguan.unizar.es/record/162752/files/texto_completo.pdf Versión publicada 3299857 http://zaguan.unizar.es/record/162752/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:162752 articulos driver 2025-10-17-14:22:02 ARTICLE