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.

项目摘要。目前，慢性，非治疗伤口正在影响超过600万美国人。 它们对患者的流动性和生活质量产生重大影响，并可能导致很高的事件 截肢和死亡率。生物膜感染是导致慢性伤口形成的关键因素。生物膜 与浮游细菌相比，细菌由于生长降低和代谢率而难以杀死， 持久细胞的存在，应对抗生素挑战的诱导抗性机制，以及 突变抗性发展。慢性伤口生物膜感染的当前临床护理标准使用 通过长时间的全身性或局部给药抗菌剂的重复调试。这种处理 效率有限，不可能对患者和医疗保健提供者造成重大燃烧。 开发抗菌剂和物理生物膜治疗的更有效的递送技术 方法是一个非常活跃的研究领域。但是，文献报价有限公司中报告的当前技术 抗生物膜效率的提高可能会对宿主组织造成潜在损害，或者需要长期 申请有效。迫切需要更高效，更安全的生物膜治疗技术 这不需要长期和经常的治疗应用来促进及时闭合慢性 伤口。 我们的长期目标是应用工程创新和技术进步，以提供更好的医疗保健 慢性伤口患者。我们在该提案中的总体目标是开发一种新颖的电流 从最初的系统提供多种慢性伤口生物膜感染的多物种的完整治疗策略 在整个伤口过程中，细菌生物负担的长期维持伤口不育的长期维持 康复。我们的系统将执行两个功能以实现这一目标：1）高 - 强度电流应用； 2）快速递送高浓缩抗生素和抗菌药物 高强度离子电池的纳米颗粒。电气调试和抗生素将达到迅速的初始 生物膜细菌的降低至伤口感染的临床阈值（105 CFU/G）。这 然后 在整个伤口愈合过程中感染。我们提出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允许安全地应用高强度电流到伤口时机 显着提高了抗生素的电气调试效率和离子遗迹递送效率和 抗菌纳米颗粒。如果成功，我们的生物膜治疗系统将对所有人产生直接的积极影响 通过显着降低伤口愈合持续时间，截肢率，患有慢性伤口的患者 与慢性伤口有关的死亡率。