Noninvasive Treatment of Biofilm on Metallic Implants

项目摘要 生物膜相关感染是用于替换或修复受伤骨骼的骨科植入物的主要并发症 和关节。生物膜是细菌和细胞外物质的聚集体，可以在任何表面上形成， 包括植入的医疗装置的表面。生物膜内的细菌被保护免受抗生素的侵害， 免疫系统，并可能导致复发性感染，即使经过长期治疗。治疗 这些感染是长期和昂贵的;删除和更换受感染的硬件，数周的抗生素 通常需要给药和延长住院时间。大约70%的生物膜- 感染是由革兰氏阳性病原体引起的，如金黄色葡萄球菌，其余的是由 革兰氏阴性病原体，如铜绿假单胞菌。抗生素耐药率上升， 这些病原体进一步使患者治疗复杂化。一种创新的非侵入性方法 金属植入物上的生物膜的处理可以通过使用交变磁场 字段（AMF）。当金属假体暴露于AMF时，在其表面上感应电流， 导致快速加热，这会破坏生物膜。这种治疗方法非常有效， 生物膜的细菌组分，并且可以与传统的抗微生物剂一起使用，以实现 彻底治疗感染。研究小组假设，体内金属的集中加热 通过AMF的递送，植入物表面将对嵌入附着的 生物膜，将增加它们对抗菌剂的敏感性，并且在体内是安全的。本项目的总体目标 研究是在小型和大型动物模型中评估通过AMF暴露的生物膜根除， 植入物感染，以及设计和表征适于治疗人AMF原型装置 植入物感染。该提案旨在回答有关最佳功率，温度， 和总暴露时间，这样既安全又有效。这将是一个重大进展， 能够原位处理植入物，避免数百万次手术和相应的数十亿美元相关费用 和他们

Project Summary Biofilm-related infections are a major complication for orthopedic implants used to replace or repair injured bones and joints. Biofilms are aggregates of bacteria and extracellular substances which can form on any surface, including the surface of implanted medical devices. Bacteria within biofilms are protected from antibiotics and the immune system, and can cause recurrent infection even after a prolonged course of therapy. The treatment of these infections is prolonged and costly; removal and replacement of the infected hardware, weeks of antibiotic administration, and extended hospital stays are usually required. Approximately 70 percent of these biofilm- infections are caused by gram-positive pathogens, such as Staphylococcus aureus, with the remaining caused by gram-negative pathogens, such as Pseudomonas aeruginosa. Increasing rates of antibiotic resistance in these pathogens are further complicating patient treatment. An innovative non-invasive approach for the treatment of biofilm on metallic implants can be achieved through the use of an alternating magnetic fields (AMF). When metal prostheses are exposed to AMF, electrical currents are induced on their surface, resulting in rapid heating which can destroy biofilm. This method of treatment is highly effective at killing the bacterial components of the biofilm, and can be used in concert with traditional antimicrobials to achieve complete treatment of the infection. The research team hypothesizes that focused heating of an in vivo metallic implant surface through the delivery of AMF will be bactericidal to pathogens embedded within an attached biofilm, will increase their sensitivity to antimicrobial agents and will be safe in vivo. The overall goals of this study are to evaluate biofilm eradication by AMF exposure in both small and large animal models of implant infection, as well as design and characterize a prototype AMF device suitable for treating human implant infections. This proposal aims to answer critical questions regarding the optimal power, temperature, and total exposure time that will be both safe and effective. This would represent a significant advance in the ability to treat implants in situ, avoiding millions of surgeries and the corresponding billions of dollars associated with them.