PMID- 33066719 OWN - NLM STAT- MEDLINE DCOM- 20211227 LR - 20220902 IS - 2162-1918 (Print) IS - 2162-1934 (Electronic) IS - 2162-1918 (Linking) VI - 10 IP - 9 DP - 2021 Sep TI - High-Voltage, Pulsed Electric Fields Eliminate Pseudomonas aeruginosa Stable Infection in a Mouse Burn Model. PG - 477-489 LID - 10.1089/wound.2019.1147 [doi] AB - Objective: The incidence of severe infectious complications after burn injury increases mortality by 40%. However, traditional approaches for managing burn infections are not always effective. High-voltage, pulsed electric field (PEF) treatment shortly after a burn injury has demonstrated an antimicrobial effect in vivo; however, the working parameters and long-term effects of PEF treatment have not yet been investigated. Approach: Nine sets of PEF parameters were investigated to optimize the applied voltage, pulse duration, and frequency or pulse repetition for disinfection of Pseudomonas aeruginosa infection in a stable mouse burn wound model. The bacterial load after PEF administration was monitored for 3 days through bioluminescence imaging. Histological assessments and inflammation response analyses were performed at 1 and 24 h after the therapy. Results: Among all tested PEF parameters, the best disinfection efficacy of P. aeruginosa infection was achieved with a combination of 500 V, 100 mus, and 200 pulses delivered at 3 Hz through two plate electrodes positioned 1 mm apart for up to 3 days after the injury. Histological examinations revealed fewer inflammatory signs in PEF-treated wounds compared with untreated infected burns. Moreover, the expression levels of multiple inflammatory-related cytokines (interleukin [IL]-1alpha/beta, IL-6, IL-10, leukemia inhibitory factor [LIF], and tumor necrosis factor-alpha [TNF-alpha]), chemokines (macrophage inflammatory protein [MIP]-1alpha/beta and monocyte chemoattractant protein-1 [MCP-1]), and inflammation-related factors (vascular endothelial growth factor [VEGF], macrophage colony-stimulating factor [M-CSF], and granulocyte-macrophage colony-stimulating factor [G-CSF]) were significantly decreased in the infected burn wound after PEF treatment. Innovation: We showed that PEF treatment on infected wounds reduces the P. aeruginosa load and modulates inflammatory responses. Conclusion: The data presented in this study suggest that PEF treatment is a potent candidate for antimicrobial therapy for P. aeruginosa burn infections. FAU - Wu, Mengjie AU - Wu M AD - Department of Orthodontics, The Affiliated Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou, China. AD - Center of Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Rubin, Andrey Ethan AU - Rubin AE AD - Porter School of Environment and Earth Sciences, Tel Aviv University, Tel Aviv, Israel. FAU - Dai, Tianhong AU - Dai T AD - Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. AD - Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Schloss, Rene AU - Schloss R AD - Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA. FAU - Usta, Osman Berk AU - Usta OB AD - Center of Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Golberg, Alexander AU - Golberg A AD - Porter School of Environment and Earth Sciences, Tel Aviv University, Tel Aviv, Israel. FAU - Yarmush, Martin AU - Yarmush M AD - Center of Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. AD - Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA. AD - Shriners Burn Hospital for Children, Boston, Massachusetts, USA. LA - eng GR - R21 AI142415/AI/NIAID NIH HHS/United States GR - R21 AI163950/AI/NIAID NIH HHS/United States GR - R21 GM136002/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20201218 PL - United States TA - Adv Wound Care (New Rochelle) JT - Advances in wound care JID - 101590593 RN - 0 (Vascular Endothelial Growth Factor A) SB - IM MH - Animals MH - Burns/complications/microbiology/*therapy MH - Disease Models, Animal MH - Disinfection/*methods MH - Electric Stimulation Therapy/*methods MH - Electrophoresis, Gel, Pulsed-Field MH - Inflammation MH - Pseudomonas Infections/*therapy MH - Pseudomonas aeruginosa MH - Sepsis/etiology/immunology MH - Tachycardia MH - Vascular Endothelial Growth Factor A MH - Wound Infection/microbiology/*therapy PMC - PMC8260897 OTO - NOTNLM OT - burn infection OT - disinfection OT - inflammation OT - pulsed electric field COIS- No competing financial interests exist. The authors listed expressly wrote the content of this article. No ghostwriters were used to write this article. EDAT- 2020/10/18 06:00 MHDA- 2021/12/28 06:00 PMCR- 2022/09/01 CRDT- 2020/10/17 05:18 PHST- 2020/10/18 06:00 [pubmed] PHST- 2021/12/28 06:00 [medline] PHST- 2020/10/17 05:18 [entrez] PHST- 2022/09/01 00:00 [pmc-release] AID - 10.1089/wound.2019.1147 [pii] AID - 10.1089/wound.2019.1147 [doi] PST - ppublish SO - Adv Wound Care (New Rochelle). 2021 Sep;10(9):477-489. doi: 10.1089/wound.2019.1147. Epub 2020 Dec 18.