Novel Electrochemical Bandage for Treatment of Wound Infections

用于治疗伤口感染的新型电化学绷带

基本信息

批准号：
10415180
负责人：
Haluk Beyenal
金额：
$ 46.87万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-05-01 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10415180
关键词：
Acinetobacter baumannii Acne Address Animal Model Animal Testing Animals Antibiotic Resistance Antibiotics Bacteria Bacterial Infections Bandage Biocide Biology Cells Chemicals Clinical Collaborations Dermal Development Devices Doctor of Philosophy Electrochemistry Electrodes Engineering Ensure Exhibits Failure Family suidae Fibroblasts Foreign Bodies Funding Genotype Genus staphylococcus Goals Grant Host Defense Human Hydrogen Peroxide Hypochlorous Acid In Vitro Individual Infection Laboratories Link Medical Medicine Methods Microbial Biofilms Microbiology Modeling Modernization Mus Orthopedics Oxygen Property Pseudomonas aeruginosa Refractory Resistance Safety Staphylococcus aureus System Technology Testing Textiles Tissues Toxic effect Wound Infection Yeasts animal tissue antimicrobial antimicrobial drug base carbon fiber clinical practice design design and construction dysbiosis experimental study flexibility in vitro activity in vivo innovation keratinocyte differentiation microorganism migration novel novel strategies novel therapeutics prevent prototype success voltage wound wound care wound healing wound treatment

项目摘要

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.

项目摘要生物膜细菌在现代临床实践中引起三分之二的感染，包括伤口和装置 - 相关感染。宿主防御和大多数可用的抗生素对生物膜无活性，使得他们引起挑战以治疗的感染。鉴于抗生素在生物膜相关的管理中失败需要感染，新颖和创新的方法。避免抗生素也会减少营养不良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策略。在原始资金期间，我们开发了“电气效应”，该效应使用固定的直流电（DC）。尽管固定的直流活动在体外和骨科异物感染的动物模型中，但对机械非特异性的担忧以及骨科感染的临床递送挑战（至少作为初始应用），导致我们提出了一种新方法。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），该策略将专门提供两个（或两者）抗生物膜化学物质 - 过氧化氢（H2O2）和/或次伐多酸（HOCL）。我们也搬到了更临床上可行的靶标 - 伤口感染。我们的新方法采用了一种完全新颖，可调的 - 电势控制 - 电化学系统，该系统将干净地提供连续的低浓度H2O2 和/或HOCL，适用于生物膜杀死，而无需损伤愈合。重要的是，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。到将生物学，微生物学，电化学，工程和动物模型专业知识汇集在一起我们的研究，我们正在与电化学家和生物膜工程师Haluk Beyenal博士新近合作。合作，我们将开发由碳纤维组成的可扩展电化学绷带（E带）将在存在特定应用潜力的情况下产生持续的，受控的H2O2和/或HOCL 提供一种易于使用的，无抗生素的方法，用于治疗受伤的伤口并促进伤口康复。在以前的资金期间，所应用的技术不可用。我们已经建立了原型产生连续的，受控浓度的H2O2或HOCL（基于应用电位）的设备减少生物膜的量。 H2O2-和HOCL生成的原型都降低了鲍曼尼杆菌，铜绿假单胞菌和金黄色葡萄球菌在体外生物膜。此外，生成HOCL 原型减少了猪真皮外植体上所有三个物种的活细菌细胞的数量， H2O2生成的原型对外植体上的鲍曼曼尼a. 组织。在AIM 1中，我们将建立电子伴侣并使用体外研究确认其生物膜治疗特性，即调整它们以确保缺乏毒性。在AIM 2中，我们将在A中展示E-Bandages的活动和安全性鼠伤口感染模型。我们的目标是在我们的研究结束时准备好产品进行人体测试。

项目成果

期刊论文数量（20）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

HOCl-producing electrochemical bandage for treating Pseudomonas aeruginosa-infected murine wounds.

产生次氯酸的电化学绷带，用于治疗铜绿假单胞菌感染的小鼠伤口。

DOI：
10.1128/aac.01216-23
发表时间：
2024
期刊：
Antimicrobial agents and chemotherapy
影响因子：
4.9
作者：
Fleming,Derek;Bozyel,Ibrahim;Ozdemir,Dilara;Otero,JudithAlvarez;Karau,MelissaJ;Anoy,MdMonzurulIslam;Koscianski,Christina;Schuetz,AudreyN;Greenwood-Quaintance,KerrylE;Mandrekar,JayawantN;Beyenal,Haluk;Patel,Robin
通讯作者：
Patel,Robin

In Vivo Activity of Hydrogen-Peroxide Generating Electrochemical Bandage Against Murine Wound Infections.

产生过氧化氢的电化学绷带对抗小鼠伤口感染的体内活性。

DOI：
10.1002/adtp.202300059
发表时间：
2023
期刊：
Advanced therapeutics
影响因子：
4.6
作者：
Raval,YashS;Fleming,Derek;Mohamed,Abdelrhman;Karau,MelissaJ;Mandrekar,JayawantN;Schuetz,AudreyN;GreenwoodQuaintance,KerrylE;Beyenal,Haluk;Patel,Robin
通讯作者：
Patel,Robin

Hypochlorous acid-generating electrochemical scaffold eliminates Candida albicans biofilms.

DOI：
10.1111/jam.14656
发表时间：
2020-10
期刊：
Journal of applied microbiology
影响因子：
4
作者：
Zmuda HM;Mohamed A;Raval YS;Call DR;Schuetz AN;Patel R;Beyenal H
通讯作者：
Beyenal H

Hypochlorous Acid-Generating Electrochemical Catheter Prototype for Prevention of Intraluminal Infection.

DOI：
10.1128/spectrum.00557-21
发表时间：
2021-10-31
期刊：
Microbiology spectrum
影响因子：
3.7
作者：
Cano EJ;Flurin L;Mohamed A;Greenwood-Quaintance KE;Raval YS;Beyenal H;Patel R
通讯作者：
Patel R

Efficacy and toxicity of hydrogen peroxide producing electrochemical bandages in a porcine explant biofilm model.