Novel lipophosphonoxin-loaded polycaprolactone electrospun nanofiber dressing reduces Staphylococcus aureus induced wound infection in mice

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.

Automated summary

The study introduces a new concept of wound dressings based on polycaprolactone nanofiber scaffold (NANO) releasing lipophosphonoxin (LPPO) as an antibacterial agent to reduce bacterial load and promote skin repair, while maintaining proliferation and differentiation of fibroblasts and keratinocytes. The NANO-LPPO dressing demonstrated antibacterial activity in vitro and significantly reduced Staphylococcus aureus counts in infected wounds in a mouse model, with facilitated degradation and LPPO release by lytic enzymes secreted by bacteria. Negligible systemic absorption of LPPO was observed, suggesting the potential for clinical application in wound treatment.