Dataset Information

Electric Field Based Dressing Disrupts Mixed-Species Bacterial Biofilm Infection and Restores Functional Wound Healing.

ABSTRACT: OBJECTIVE:This study was designed to employ electroceutical principles, as an alternative to pharmacological intervention, to manage wound biofilm infection. Mechanism of action of a United States Food and Drug Administration-cleared wireless electroceutical dressing (WED) was tested in an established porcine chronic wound polymicrobial biofilm infection model involving inoculation with Pseudomonas aeruginosa PAO1 and Acinetobacter baumannii 19606. BACKGROUND:Bacterial biofilms represent a major wound complication. Resistance of biofilm toward pharmacologic interventions calls for alternative therapeutic strategies. Weak electric field has anti-biofilm properties. We have previously reported the development of WED involving patterned deposition of Ag and Zn on fabric. When moistened, WED generates a weak electric field without any external power supply and can be used as any other disposable dressing. METHODS:WED dressing was applied within 2?hours of wound infection to test its ability to prevent biofilm formation. Alternatively, WED was applied after 7 days of infection to study disruption of established biofilm. Wounds were treated with placebo dressing or WED twice a week for 56 days. RESULTS:Scanning electron microscopy demonstrated that WED prevented and disrupted wound biofilm aggregates. WED accelerated functional wound closure by restoring skin barrier function. WED blunted biofilm-induced expression of (1) P. aeruginosa quorum sensing mvfR (pqsR), rhlR and lasR genes, and (2) miR-9 and silencing of E-cadherin. E-cadherin is critically required for skin barrier function. Furthermore, WED rescued against biofilm-induced persistent inflammation by circumventing nuclear factor kappa B activation and its downstream cytokine responses. CONCLUSION:This is the first pre-clinical porcine mechanistic study to recognize the potential of electroceuticals as an effective platform technology to combat wound biofilm infection.

SUBMITTER: Barki KG

PROVIDER: S-EPMC6568008 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Publications

Electric Field Based Dressing Disrupts Mixed-Species Bacterial Biofilm Infection and Restores Functional Wound Healing.

Barki Kasturi Ganesh KG Das Amitava A Dixith Sriteja S Ghatak Piya Das PD Mathew-Steiner Shomita S Schwab Elizabeth E Khanna Savita S Wozniak Daniel J DJ Roy Sashwati S Sen Chandan K CK

Annals of surgery 20190401 4

<h4>Objective</h4>This study was designed to employ electroceutical principles, as an alternative to pharmacological intervention, to manage wound biofilm infection. Mechanism of action of a United States Food and Drug Administration-cleared wireless electroceutical dressing (WED) was tested in an established porcine chronic wound polymicrobial biofilm infection model involving inoculation with Pseudomonas aeruginosa PAO1 and Acinetobacter baumannii 19606.<h4>Background</h4>Bacterial biofilms re ...[more]

PMID: 29099398

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Project description:Cationic antimicrobial peptides are multifunctional molecules that have a high potential as therapeutic agents. We have identified a histone H1-derived peptide from the Komodo dragon (Varanus komodoensis), called VK25. Using this peptide as inspiration, we designed a synthetic peptide called DRGN-1. We evaluated the antimicrobial and anti-biofilm activity of both peptides against Pseudomonas aeruginosa and Staphylococcus aureus. DRGN-1, more than VK25, exhibited potent antimicrobial and anti-biofilm activity, and permeabilized bacterial membranes. Wound healing was significantly enhanced by DRGN-1 in both uninfected and mixed biofilm (Pseudomonas aeruginosa and Staphylococcus aureus)-infected murine wounds. In a scratch wound closure assay used to elucidate the wound healing mechanism, the peptide promoted the migration of HEKa keratinocyte cells, which was inhibited by mitomycin C (proliferation inhibitor) and AG1478 (epidermal growth factor receptor inhibitor). DRGN-1 also activated the EGFR-STAT1/3 pathway. Thus, DRGN-1 is a candidate for use as a topical wound treatment. Wound infections are a major concern; made increasingly complicated by the emerging, rapid spread of bacterial resistance. The novel synthetic peptide DRGN-1 (inspired by a peptide identified from Komodo dragon) exhibits pathogen-directed and host-directed activities in promoting the clearance and healing of polymicrobial (Pseudomonas aeruginosa & Staphylococcus aureus) biofilm infected wounds. The effectiveness of this peptide cannot be attributed solely to its ability to act upon the bacteria and disrupt the biofilm, but also reflects the peptide's ability to promsote keratinocyte migration. When applied in a murine model, infected wounds treated with DRGN-1 healed significantly faster than did untreated wounds, or wounds treated with other peptides. The host-directed mechanism of action was determined to be via the EGFR-STAT1/3 pathway. The pathogen-directed mechanism of action was determined to be via anti-biofilm activity and antibacterial activity through membrane permeabilization. This novel peptide may have potential as a future therapeutic for treating infected wounds.

Project description:Due to the transepidermal potential of 15-50?mV, inside positive, an injury current is driven out of all human skin wounds. The flow of this current generates a lateral electric field within the epidermis that is more negative at the wound edge than at regions more lateral from the wound edge. Electric fields in this region could be as large as 40?mV/mm, and electric fields of this magnitude have been shown to stimulate human keratinocyte migration toward the wounded region. After flowing out of the wound, the current returns through the space between the epidermis and stratum corneum, generating a lateral field above the epidermis in the opposite direction. Here, we report the results from the first clinical trial designed to measure this lateral electric field adjacent to human skin wounds noninvasively. Using a new instrument, the Dermacorder®, we found that the mean lateral electric field in the space between the epidermis and stratum corneum adjacent to a lancet wound in 18-25-year-olds is 107-148?mV/mm, 48% larger on average than that in 65-80-year-olds. We also conducted extensive measurements of the lateral electric field adjacent to mouse wounds as they healed and compared this field with histological sections through the wound to determine the correlation between the electric field and the rate of epithelial wound closure. Immediately after wounding, the average lateral electric field was 122?±?9?mV/mm. When the wound is filled in with a thick, disorganized epidermal layer, the mean field falls to 79?±?4?mV/mm. Once this epidermis forms a compact structure with only three cell layers, the mean field is 59?±?5?mV/mm. Thus, the peak-to-peak spatial variation in surface potential is largest in fresh wounds and slowly declines as the wound closes. The rate of wound healing is slightly greater when wounds are kept moist as expected, but we could find no correlation between the amplitude of the electric field and the rate of wound healing.

Dataset Information

Electric Field Based Dressing Disrupts Mixed-Species Bacterial Biofilm Infection and Restores Functional Wound Healing.

Publications

Electric Field Based Dressing Disrupts Mixed-Species Bacterial Biofilm Infection and Restores Functional Wound Healing.

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