Noninvasive Treatment of Biofilm on Metallic Implants

项目摘要 生物膜相关感染是骨科植入物替换或修复受损骨骼的主要并发症。 和关节。生物膜是细菌和胞外物质的聚集体，可以在任何表面形成， 包括植入的医疗器械的表面。生物膜内的细菌被保护不受抗生素和 会影响免疫系统，即使经过长时间的治疗也会导致复发感染。治疗方法 这些感染是漫长和昂贵的；拆卸和更换受感染的硬件，数周的抗生素 管理，并延长住院时间通常是需要的。其中约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 由革兰氏阴性病原体引起，如铜绿假单胞菌。抗生素耐药率不断上升 这些病原体使患者的治疗进一步复杂化。一种创新的非侵入性方法，用于 金属植入物上生物膜的处理可以通过使用交变磁场来实现。 字段(AMF)。当金属假体暴露在AMF中时，其表面会产生电流， 导致快速加热，这可能会破坏生物膜。这种治疗方法对杀死 细菌成分的生物被膜，并可与传统的抗菌剂协同使用，实现 彻底治疗感染。研究小组假设，体内金属的聚焦加热 种植体表面通过输送AMF将杀菌作用嵌入病原体内附着 生物被膜，将增加他们对抗菌剂的敏感性，在体内将是安全的。这个项目的总体目标是 这项研究是评估AMF暴露在小动物模型和大动物模型中的生物被膜消除情况 以及适合于治疗人类的AMF装置的原型的设计和表征 植入物感染。这项建议旨在回答有关最佳功率、温度、 和总暴露时间，这将是安全和有效的。这将代表着在 能够就地治疗植入物，避免数百万次手术和相应的数十亿美元相关费用 和他们在一起。

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.