Novel Electrochemical Bandage for Treatment of Wound Infections

项目摘要 在现代临床实践中，生物膜细菌引起三分之二的感染，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是无活性的， 由于抗生素在管理生物膜相关的感染方面的失败， 感染，需要新的和创新的方法。避免抗生素也会减少生态失调 以及与其使用相关的基因型抗生素抗性的选择。我们正在开发电抗生物膜 战略布局在最初的资助时期，我们开发了“杀电效应”，它使用固定的直流电， （DC）。虽然固定的DC在体外和骨科异物感染的动物模型中表现出活性， 对机制非特异性的担忧，以及骨科感染临床治疗的挑战（至少 作为一个初始应用程序），导致我们提出了一个新的方法。在这里，我们提出了一个机械精确的 电化学策略（与固定DC不同），其将特异性地递送两种中的一种或另一种（或两者）。 抗生物膜化学品-过氧化氢（H2 O2）和/或次氯酸（HOCl）。我们也搬到了一个 临床上更可行的目标伤口感染。我们的新方法采用了一种全新的，可调的- 电位控制的电化学系统，其将清洁地提供连续低浓度的H2 O2 和/或HOCl，适用于生物膜杀灭，而不损害伤口愈合。重要的是，这两种化学物质都具有 它们在伤口护理中的应用，但由于它们的原始化学形式的快速分解而阻碍了使用。到 汇集了生物学，微生物学，电化学，工程和动物模型所需的专业知识， 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 合作，我们将开发可扩展的电化学绷带（电子绷带）组成的碳纤维， 将在特定的外加电势存在下产生持续的、受控量的H2 O2和/或HOCl， 提供了一种易于使用的、不含抗生素的方法来治疗感染的伤口和促进伤口愈合， 治愈上一个供资期没有采用的技术。我们已经建立了原型 产生连续、受控浓度的H2 O2或HOCl（基于施加的电势）的装置， 减少生物膜的量。产生H2 O2和HOCl的原型都减少了鲍曼不动杆菌， 铜绿假单胞菌和金黄色葡萄球菌体外生物膜。此外，HOCl生成 原型减少了猪皮肤外植体上所有三个物种的活细菌细胞的数量， 产生H2 O2的原型对A.在不损伤动物的情况下， 组织.在目标1中，我们将构建电子绷带，并使用体外研究确认其生物膜治疗特性， 调整它们以确保没有毒性。在目标2中，我们将证明电子绷带在 小鼠伤口感染模型。我们的目标是在我们的研究结束时准备好一种用于人体测试的产品。

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.