Electric Field Based Dressing Disrupts Mixed-Species Bacterial Biofilm Infection and Restores Functional Wound Healing.
Electric Field Based Dressing Disrupts Mixed-Species Bacterial Biofilm Infection and Restores Functional Wound Healing.
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DOI：
10.1097/sla.0000000000002504
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发表时间：
2019-04
影响因子：
9
通讯作者：
Sen CK
中科院分区：
文献类型：
--
作者：
Barki KG;Das A;Dixith S;Ghatak PD;Mathew-Steiner S;Schwab E;Khanna S;Wozniak DJ;Roy S;Sen CK
本研究旨在采用电化学原理，作为药物干预的替代方案，以管理伤口生物膜感染。在已建立的猪慢性伤口多微生物生物膜感染模型（包括接种铜绿假单胞菌PAO 1和鲍曼不动杆菌19606）中，对美国食品药品监督管理局批准的无线电敷料（WED）的作用机制进行了测试。细菌生物膜是一种主要的伤口并发症。生物膜对药物干预的耐药性要求替代治疗策略。弱电场具有抗生物膜的特性。我们以前曾报道的发展WED涉及图案化沉积的Ag和Zn的织物。当湿润时，WED在没有任何外部电源的情况下产生弱电场，并且可以用作任何其他一次性敷料。在伤口感染的2小时内施用WED敷料以测试其防止生物膜形成的能力。或者，在感染7天后应用WED以研究建立的生物膜的破坏。伤口用安慰剂敷料或WED治疗，每周两次，持续56天。扫描电子显微镜表明，WED防止和破坏伤口生物膜聚集体。WED通过恢复皮肤屏障功能加速功能性伤口闭合。WED减弱了生物膜诱导的（1）铜绿假单胞菌群体感应mvfR（pqsR）、rhlR和lasR基因的表达，以及（2）miR-9和E-钙粘蛋白的沉默。E-钙粘蛋白是皮肤屏障功能所必需的。此外，WED通过规避核因子κ B活化及其下游细胞因子应答来挽救生物膜诱导的持续性炎症。这是第一个临床前猪机制研究，以认识到电化学品作为对抗伤口生物膜感染的有效平台技术的潜力。
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. 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. 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. 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. 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.