A novel electric current-based treatment system for chronic wound biofilm infections

一种新型的基于电流的慢性伤口生物膜感染治疗系统

• 批准号: 10720191
• 负责人: Siwei Zhao
• 金额: $ 37.77万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-07 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10720191
• 关键词: Acceleration; Affect; Aftercare; American; Amputation; Antibiotics; Area; Bacteria; Bacterial Counts; Cells; Characteristics; Chronic; Clinical; Debridement; Development; Devices; Engineering; Family suidae; Goals; Growth; Health Personnel; Healthcare; Hour; Hydrogels; Incidence; Infection; Inflammatory; Iontophoresis; Lead; Literature; Maintenance; Medical; Methods; Microbial Biofilms; Mission; National Institute of Biomedical Imaging and Bioengineering; Outcome; Patients; Pharmaceutical Preparations; Phase; Process; Public Health; Quality of life; Reporting; Research; Research Project Grants; Resistance development; Resources; Safety; Societies; Sterility; System; Technology; Therapeutic Effect; Tissues; Topical application; Wound Infection; antimicrobial; antimicrobial drug; bioelectricity; chronic wound; clinical application; combat; cost; healing; improved; in vivo; innovation; metabolic rate; methicillin resistant Staphylococcus aureus; mortality; nanoparticle; non-healing wounds; novel; patient mobility; polymicrobial biofilm; prevent; resistance mechanism; resistance mutation; response; skin wound; standard of care; treatment strategy; wound; wound biofilm; wound care; wound healing

PROJECT SUMMARY. Chronic, non-healing wounds are currently affecting more than 6 million Americans. They have significant impact on patients’ mobility and quality of life, and can lead to a high incidence of amputation and mortality rate. Biofilm infection is a critical factor that leads to chronic wound formation. Biofilm bacteria are very difficult to kill compared to planktonic bacteria due to their reduced growth and metabolic rates, the presence of persister cells, inducible resistance mechanisms in response to antibiotic challenges, and the mutational resistance development. Current clinical standard of care for chronic wound biofilm infections uses repeated debridement with prolonged systemic or topical administration of antimicrobial agents. This treatment has limited efficacy and imposes a significant burden on both patients and healthcare providers. The development of more effective delivery technologies for antimicrobial agents and physical biofilm treatment methods is a very active research area. However, current technologies reported in the literature offer limited improvement in anti-biofilm efficacy, may cause potential damage to host tissues, or require a long-term application to be effective. There is a critical need for more efficacious and safer biofilm treatment technologies that does not require long-duration and frequent treatment applications to facilitate a timely closure of chronic wounds. Our long-term goal is to apply engineering innovations and technological advances to providing better healthcare to chronic wound patients. Our overall objective in this proposal is to develop a novel, electric current-based system to provide a complete treatment strategy for multispecies chronic wound biofilm infections from the initial reduction of bacterial bioburden to the long-term maintenance of wound sterility during the entire course of wound healing. Our system will perform two functions to achieve this goal: 1) electrical debridement of biofilm by high- intensity electric current application; and 2) rapid delivery of high-concentration antibiotics and antimicrobial nanoparticles by high-intensity iontophoresis. The electrical debridement and antibiotics will achieve a rapid initial reduction of biofilm bacterial count to below the clinical threshold for wound infection (105 CFU/g). The antimicrobial nanoparticles will then maintain a low bacterial bioburden, prevent biofilm reformation and new infections throughout the wound healing process. Our proposed system will be based on a novel hydrogel ionic circuit technology developed in our lab to allow safe application of high-intensity current to wound tissues to significantly enhance electrical debridement efficacy and iontophoretic delivery efficiency for antibiotics and antimicrobial nanoparticles. If successful, our biofilm treatment system will have direct positive impact on all patients suffering from chronic wounds by significantly reducing the wound healing duration, the amputation rate and mortality rate associated with chronic wounds.

项目总结。慢性的、无法愈合的伤口目前正在影响600多万美国人。 它们对患者的行动能力和生活质量有重大影响，并可导致高发病率 截肢和死亡率。生物膜感染是导致慢性创面形成的关键因素。生物膜 与浮游细菌相比，细菌很难杀死，因为它们的生长和代谢率降低， 永生化细胞的存在，对抗生素挑战的可诱导耐药机制，以及 突变抗药性的发展。慢性创面生物被膜感染的现行临床护理标准 反复清创，长期全身或局部使用抗菌药物。这种治疗方法 疗效有限，给患者和医疗保健提供者都带来了沉重的负担。这个 开发更有效的抗菌剂输送技术和物理生物膜处理 方法是一个非常活跃的研究领域。然而，文献中报告的当前技术提供的有限 提高抗生物被膜的功效，可能会对宿主组织造成潜在的损害，或需要长期 申请是有效的。迫切需要更有效、更安全的生物膜处理技术。 这不需要长时间和频繁的治疗应用，以促进及时关闭慢性 伤口。 我们的长期目标是应用工程创新和技术进步来提供更好的医疗保健 给慢性伤口患者。我们在这项提议中的总体目标是开发一种新颖的、基于电流的 系统从一开始就为多种慢性伤口生物被膜感染提供完整的治疗策略 减少细菌生物负荷，长期维持创面全过程无菌 治愈。我们的系统将执行两个功能来实现这一目标：1)电清除生物膜。 2)高浓度抗生素和抗菌剂的快速输送 纳米粒子通过高强度离子导入。电清创术和抗生素治疗将迅速取得初步疗效 将生物被膜细菌数量降至伤口感染的临床阈值以下(105cfu/g)。这个 抗菌纳米粒则会保持较低的细菌生物量，防止生物被膜的重新形成和新 在伤口愈合过程中一直受到感染。我们建议的系统将基于一种新型的水凝胶离子 我们实验室开发的电路技术可以安全地将高强度电流应用于伤口组织 显著提高抗生素的电清创效率和离子导入效率 抗菌纳米颗粒。如果成功，我们的生物膜处理系统将对所有 对患有慢性创面的患者可显著缩短创面愈合时间、截肢率 以及与慢性伤口相关的死亡率。