Novel Electrochemical Bandage for Treatment of Wound Infections

项目总结 在现代临床实践中，生物被膜细菌导致了三分之二的感染，包括伤口和器械- 相关感染。宿主防御和大多数可用的抗生素对生物膜不起作用，导致 他们造成的感染治疗起来很有挑战性。鉴于抗生素在生物被膜相关治疗中的失败 感染、新的和创新的方法是必要的。避免使用抗生素也会减少生物失调。 以及与其使用相关的基因型别抗生素耐药性的选择。我们正在开发电抗生物膜 战略。在最初的资助期间，我们开发了使用固定直流电的“电击效应”。 (DC)。尽管固定的DC在体外和骨科异物感染的动物模型中显示出活性， 对机械性非特异性的担忧，以及在骨科感染的临床交付方面的挑战(至少 作为最初的应用)，使我们提出了一种新的方法。在这里，我们提出了一个机械上精确的 电化学策略(不同于固定DC)，它将专门提供两种中的一种或另一种(或两者) 抗生物被膜化学品-过氧化氢(H_2O_2)和/或次氯酸(HOCl)。我们还搬到了一个 临床上更可行的靶向伤口感染。我们的新方法采用了一种全新的、可调节的- 电位控制的电化学系统，它将清洁地提供持续的低浓度过氧化氢 和/或HOCl，适用于生物膜杀灭，而不影响伤口愈合。重要的是，这两种化学物质都有 在伤口护理中的应用，但由于其原始化学形式的快速分解而阻碍了使用。至 将生物学、微生物学、电化学、工程和动物模型所需的专业知识结合起来 在我们的研究中，我们最近与电化学家和生物膜工程师Haluk Beyenal博士合作。在……里面 合作，我们将开发可扩展的电化学绷带(e-绷带)，由碳纤维组成， 将在特定的施加电位存在的情况下产生持续的、受控量的过氧化氢和/或HOCl2， 提供一种易于使用、不含抗生素的方法来治疗感染伤口和促进伤口愈合 治愈。所应用的技术在上一个供资期间无法获得。我们已经制作了原型 产生持续、受控浓度的过氧化氢或高氯酸根的装置(基于施加的电位) 减少生物膜的数量。过氧化氢和高氯酸盐产生的原型都能减少鲍曼不动杆菌， 铜绿假单胞菌和金黄色葡萄球菌生物膜的体外培养。此外，HOCl-生成 Prototype减少了所有三个物种在猪皮肤外植体上的活细菌细胞数量，并且 在外植体上产生过氧化氢的原型对鲍曼不动杆菌也起到了同样的作用，而不会对动物造成损害。 组织。在目标1中，我们将建造电子绷带，并使用体外研究确认其生物膜处理特性， 调整它们以确保没有毒性。在目标2，我们将演示电子绷带的活性和安全性 小鼠创面感染模型。我们的目标是在研究结束时将一种产品准备好进行人体测试。

PROJECT SUMMARY Biofilm bacteria cause two-thirds of infections in modern clinical practice, including wound and device- related infections. Host defenses and most available antibiotics are inactive against biofilms, rendering the infections they cause challenging to treat. Given the failure of antibiotics in management of biofilm-associated infections, novel and innovative approaches are needed. Avoiding antibiotics will also decrease the dysbiosis and selection of genotypic antibiotic resistance linked to their use. We are developing electrical anti-biofilm strategies. In the original funding period, we developed the “electricidal effect,” which uses fixed direct current (DC). Though fixed DC exhibited activity in vitro and in animal models of orthopedic foreign body infection, concerns about mechanistic non-specificity, and challenges in clinical delivery for orthopedic infections (at least as an initial application), led us to propose a new approach. Here, we propose a mechanistically-precise electrochemical strategy (distinct from fixed DC), that will specifically deliver one or the other (or both) of two anti-biofilm chemicals – hydrogen peroxide (H2O2) and/or hypochlorous acid (HOCl). We have also moved to a more clinically feasible target – wound infections. Our new approach employs a completely novel, tunable – potential-controlled – electrochemical system, which will cleanly deliver continuous low concentrations of H2O2 and/or HOCl, suitable for biofilm killing, without compromising wound healing. Importantly, both chemicals have applications in wound care, but use has been hindered by rapid decomposition of their raw chemical forms. To bring together the biology, microbiology, electrochemistry, engineering and animal model expertise required for our studies, we are newly collaborating with an electrochemist and biofilm engineer, Haluk Beyenal, PhD. In collaboration, we will develop scalable electrochemical bandages (e-bandages) composed of carbon fibers that will generate sustained, controlled quantities of H2O2 and/or HOCl in the presence of specific applied potential, providing an easy-to-use, antibiotic-free approach for treatment of infected wounds and promotion of wound healing. The technology being applied was not available in the prior funding period. We have built prototype devices that generate continuous, controlled concentrations of H2O2 or HOCl (based on applied potential) in amounts that reduce biofilms. Both H2O2- and HOCl-generating prototypes reduced Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus biofilms in vitro. Further, the HOCl-generating prototype reduced the number of live bacterial cells of all three species on porcine dermal explants, and the H2O2-generating prototype did the same against A. baumannii on explants, without damaging the animal tissue. In Aim 1, we will build e-bandages and confirm, using in vitro studies, their biofilm treatment properties, tuning them to ensure lack of toxicity. In Aim 2, we will demonstrate activity and safety of the e-bandages in a murine wound infection model. Our goal is to have a product ready for human testing at the end of our studies.