The Ohio State University Comprehensive Wound Center, Center for Regenerative Medicine and Cell Based Therapies, Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH.
The Ohio State University, Department of Microbial Infection and Immunity, Department of Microbiology, Center for Microbial Interface Biology, The Ohio State University, Columbus, OH.
Ann Surg. 2019 Apr;269(4):756-766. doi: 10.1097/SLA.0000000000002504.
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.
本研究旨在采用电疗原理，作为药物干预的替代方法，来治疗伤口生物膜感染。美国食品和药物管理局批准的无线电疗敷料（WED）的作用机制在涉及接种铜绿假单胞菌 PAO1 和鲍曼不动杆菌 19606 的已建立的猪慢性伤口多微生物生物膜感染模型中进行了测试。
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需要替代治疗策略。弱电场具有抗生物膜特性。我们之前报道了涉及在织物上图案沉积 Ag 和 Zn 的 WED 的开发。当湿润时，WED 会产生弱电场，而无需任何外部电源，并且可以像任何其他一次性敷料一样使用。
在伤口感染后 2 小时内应用 WED 敷料，以测试其预防生物膜形成的能力。或者，在感染后 7 天应用 WED 敷料以研究破坏已建立的生物膜。伤口每周用安慰剂敷料或 WED 治疗两次，共 56 天。
扫描电子显微镜显示，WED 可预防和破坏伤口生物膜聚集物。WED 通过恢复皮肤屏障功能加速了功能性伤口闭合。WED 抑制了生物膜诱导的（1）铜绿假单胞菌群体感应 mvfR（pqsR）、rhlR 和 lasR 基因，和（2）miR-9 和 E-钙黏蛋白的沉默。E-钙黏蛋白对于皮肤屏障功能至关重要。此外，WED 通过绕过核因子 kappa B 激活及其下游细胞因子反应，防止生物膜诱导的持续性炎症。
这是第一项识别电疗作为有效平台技术来对抗伤口生物膜感染的潜在性的临床前猪机制研究。
