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

项目摘要。慢性、不愈合的伤口目前影响着600多万美国人。 它们对患者的活动性和生活质量有显著影响，并可导致高发病率， 截肢率和死亡率。生物膜感染是导致慢性伤口形成的关键因素。生物膜 细菌由于其降低的生长和代谢速率而与嗜盐细菌相比非常难以杀死， 持续存在的细胞，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现行临床护理标准 反复清创，并长期全身或局部给予抗菌剂。这种治疗 具有有限的功效，并且对患者和健康护理提供者都造成很大的负担。的 开发用于抗菌剂和物理生物膜处理的更有效的递送技术 方法是一个非常活跃的研究领域。然而，文献中报道的当前技术提供了有限的 抗生物膜功效的改善可能对宿主组织造成潜在的损伤，或者需要长期的 应用要有效。迫切需要更有效和更安全的生物膜处理技术 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 我们的长期目标是将工程创新和技术进步应用于提供更好的医疗保健 慢性创伤患者。我们在这个提案中的总体目标是开发一种新颖的，基于电流的 该系统为多物种慢性伤口生物膜感染提供了一个完整的治疗策略， 在整个伤口过程中减少细菌生物负载以长期维持伤口无菌性 治愈我们的系统将执行两个功能来实现这一目标：1）通过高- 高强度电流应用;和2）高浓度抗生素和抗微生物剂的快速递送 纳米粒子通过高强度离子电渗。电清创术和抗生素将实现快速初始化 生物膜细菌计数降低至低于伤口感染的临床阈值（105 CFU/g）。的 然后，抗微生物纳米颗粒将保持低的细菌生物负荷，防止生物膜重新形成， 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的水凝胶离子 在我们的实验室开发的电路技术，允许安全应用高强度电流的伤口组织， 显著提高了电清创功效和抗生素的离子电渗递送效率， 抗微生物纳米颗粒。如果成功，我们的生物膜处理系统将对所有人产生直接的积极影响。 患有慢性伤口的患者，伤口愈合时间明显缩短，截肢率 以及与慢性伤口相关的死亡率。

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.