Multifunctional Antimicrobial Nanofiber Dressings Containing ε-Polylysine for the Eradication of Bacterial Bioburden and Promotion of Wound Healing in Critically Colonized Wounds.

Bacterial colonization of acute and chronic wounds is often associated with delayed wound healing and prolonged hospitalization. The rise of multi-drug resistant bacteria and the poor biocompatibility of topical antimicrobials warrant safe and effective antimicrobials. Antimicrobial agents that target microbial membranes without interfering with the mammalian cell proliferation and migration hold great promise in the treatment of traumatic wounds. This article reports the utility of superhydrophilic electrospun gelatin nanofiber dressings (NFDs) containing a broad-spectrum antimicrobial polymer, ε-polylysine (εPL), crosslinked by polydopamine (pDA) for treating second-degree burns. In a porcine model of partial thickness burns, NFDs promoted wound closure and reduced hypertrophic scarring compared to untreated burns. Analysis of NFDs in contact with the burns indicated that the dressings trap early colonizers and elicit bactericidal activity, thus creating a sterile wound bed for fibroblasts migration and re-epithelialization. In support of these observations, in porcine models of Pseudomonas aeruginosa and Staphylococcus aureus colonized partial thickness burns, NFDs decreased bacterial bioburden and promoted wound closure and re-epithelialization. NFDs displayed superior clinical outcome than standard-of-care silver dressings. The excellent biocompatibility and antimicrobial efficacy of the newly developed dressings in pre-clinical models demonstrate its potential for clinical use to manage infected wounds without compromising tissue regeneration.

Combating Microbial Contamination with Robust Polymeric Nanofibers: Elemental Effect on the Mussel-Inspired Cross-Linking of Electrospun Gelatin.

Designing biocompatible nanofibrous mats capable of preventing microbial colonization from resident and nosocomial bacteria for an extended period remains an unmet clinical need. In the present work, we designed antibiotic free durable antimicrobial nanofiber mats by taking advantage of synergistic interactions between polydopamine (pDA) and metal ions with varying degree of antimicrobial properties (Ag+, Mg2+, Ca2+, and Zn2+). Microscopic analysis showed successful pDA-mediated cross-linking of the gelatin nanofibers, which further improved by the inclusion of Ag+, Mg2+, and Ca2+ ions as supported by mechanical and thermal studies. Spectroscopic results reinforce the presence of strong interactions between pDA and metal ions in the composite nanofibers, leading to generation of robust polymeric nanofibers. We further showed that strong pDA-Ag interactions attenuated the cell cytotoxicity and anticell proliferative properties of silver ions for immortalized keratinocytes and primary human dermal fibroblasts. pDA-Ca2+/Zn2+ interactions rendered the composite structure sterile against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium strains, whereas the silver ion-incorporated composite mats displayed broad spectrum antibacterial activity against both Gram-positive/-negative bacteria and yeast strains. We showed that the strong pDA-Ag interactions help retaining long-term antimicrobial activity of the mats for at least 40 days while attenuating mammalian cell cytotoxicity of silver ions for skin cells. Overall, the results suggest the potential of pDA-metal ion interactions for engineering sterile nanofibrous mats and expanding the antibiotic armamentarium against drug-resistant pathogens.