Active wound dressings are attracting extensive attention in soft tissue repair and regeneration, including bacteria-infected skin wound healing. As the wide use of antibiotics leads to drug resistance we present here a new concept of wound dressings based on the polycaprolactone nanofiber scaffold (NANO) releasing second generation lipophosphonoxin (LPPO) as antibacterial agent. Firstly, we demonstrated in vitro that LPPO released from NANO exerted antibacterial activity while not impairing proliferation/differentiation of fibroblasts and keratinocytes. Secondly, using a mouse model we showed that NANO loaded with LPPO significantly reduced the Staphylococcus aureus counts in infected wounds as evaluated 7 days post-surgery. Furthermore, the rate of degradation and subsequent LPPO release in infected wounds was also facilitated by lytic enzymes secreted by inoculated bacteria. Finally, LPPO displayed negligible to no systemic absorption. In conclusion, the composite antibacterial NANO-LPPO-based dressing reduces the bacterial load and promotes skin repair, with the potential to treat wounds in clinical settings.

Department of Biomedical Research East Slovak Institute of Cardiovascular Diseases Ondavská 8 040 11 Košice Slovak Republic

Department of Medical Microbiology 2nd Faculty of Medicine Charles University 5 Úvalu 84 150 06 Prague 5 Czech Republic

Faculty of Science Humanities and Education Technical University of Liberec Studentska 1402 2 461 17 Liberec 1 Czech Republic

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Flemingovo nám 2 166 10 Prague 6 Czech Republic

Laboratory of Bacterial Genetics Centre for Epidemiology and Microbiology National Institute of Public Health Šrobárova 49 48 100 00 Prague 10 Czech Republic

Laboratory of Cell Interactions Center of Clinical and Preclinical Research MediPark Pavol Jozef Šafárik University Trieda SNP 1 040 11 Košice Slovak Republic

Laboratory of Microbial Genetics and Gene Expression Institute of Microbiology Czech Academy of Sciences 5 V 1 Vídeňská 1083 142 20 Prague 4 Czech Republic

Prague Burn Centre 3rd Faculty of Medicine University Hospital Královské Vinohrady Šrobárova 50 100 34 Prague 10 Czech Republic

The Institute for Nanomaterials Advanced Technologies and Innovation Bendlova 1409 7 460 01 Liberec 1 Czech Republic

Unit for Biomedicine and Welfare of Laboratory Animals National Institute of Public Health Šrobárova 49 48 100 00 Prague 10 Czech Republic

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