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

Abstract

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.

Electrospun polycaprolactone nanofibrous membranes loaded with baicalin for antibacterial wound dressing

“…PCL has received considerable attention due to its high toughness, biodegradability, and biocompatibility. It has been demonstrated that electrospun PCL nanofibrous scaffolds can be utilized for wound dressing applications 9 – 11 . The native porous structure characteristics of PCL scaffolds can mimic the skin's extracellular matrix (ECM) structural properties while also providing high oxygen permeability.…”

Iron-Based Magnetic Nanosystems for Diagnostic Imaging and Drug Delivery: Towards Transformative Biomedical Applications

“…Fibres consisting of a polymer base along with MNPs have been investigated for numerous biomedical applications, including drug-carrying vehicles, advanced scaffolds for tissue engineering and bases for wound dressing [ 71 , 72 , 73 ] ( Figure 7 ). The morphology of such nanoscale fibres resembles biological tissue, and as a result they are of particular interest in biomedicine.…”

“… Diversity and versatility of MNP incorporated fibre based magnetic nanosystems in terms of synthesis, fibre morphology and scope of applications. Reproduced with permission from: ( A )—Do Pham et al, 2021 [ 72 ]. ( B )—Perera et al, 2018 Copyright © 2022 American Chemical Society [ 11 ].…”

LEGO-lipophosphonoxins: length of hydrophobic module affects permeabilizing activity in target membranes of different phospholipid composition

“…19,20 LPPO II has already been successfully evaluated as an antibacterial additive in the bone cement 21 and as a wound dressings based on the polycaprolactone nanober scaffold (NANO) releasing second generation lipophosphonoxin (LPPO) as the antibacterial agent. 22 Major structural alteration led to the newest generation called LEGO-LPPO, 23 which demonstrated activity against both G + and G − bacteria, and improved selectivity. Moreover, their activity is not inuenced by the presence of serum albumins that presented complications in previous LPPO generations.…”