Noninvasive Treatment of Biofilm on Metallic Implants

金属植入物上生物膜的无创治疗

• 批准号: 10263362
• 负责人: Rajiv Chopra
• 金额: $ 75.92万
• 依托单位: SOLENIC MEDICAL INC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-14 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10263362
• 关键词: Adjuvant; Animal Model; Antibiotic Resistance; Antibiotic Therapy; Antibiotics; Bacteria; Bacterial Drug Resistance; Biomedical Engineering; Bone Growth; Bone Injury; Clinical; Clinical Trials; Collection; Communicable Diseases; Complement; Complication; Cyclic GMP; Data; Data Set; Development; Devices; Documentation; Engineering; Excision; Exposure to; Face; Feedback; Financial Hardship; Fright; Goals; Healthcare Systems; Heating; Hospitals; Human; Immune system; Implant; In Situ; In Vitro; Incidence; Industry; Infection; Institution; Intervention; Joint Prosthesis; Joints; Length of Stay; Medical; Medical Device; Medical center; Metals; Methods; Microbial Biofilms; Morbidity - disease rate; Mus; Operative Surgical Procedures; Orthopedics; Outpatients; Patients; Perioperative; Precision therapeutics; Procedures; Process; Prosthesis; Pseudomonas aeruginosa; Public Health; Research; Research Personnel; Risk Management; Safety; Scientist; Staphylococcus aureus; Surface; System; Technology; Temperature; Testing; Texas; Time; Toxic effect; Trauma; Treatment Failure; Universities; Validation; Veterans; antimicrobial; antimicrobial drug; bactericide; base; cost; design; design and construction; drug efficacy; extracellular; in vivo; injury and repair; innovation; joint infection; magnetic field; medical implant; meetings; metallicity; new technology; pathogen; portability; pre-clinical; programs; prototype; recurrent infection; safety testing; sheep model; simulation; standard of care; synergism

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.

项目摘要 生物膜相关感染是用于替代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，可以在任何表面形成， 包括植入医疗设备的表面。生物膜内的细菌受到保护免受抗生素的保护和 免疫系统，即使经过长时间的治疗，也可能引起复发感染。治疗 这些感染的延长和昂贵；去除和替换感染的硬件，数周的抗生素 通常需要管理和延长医院住院。这些生物膜中约有70％ 感染是由革兰氏阳性病原体（例如金黄色葡萄球菌）引起的，其余引起的 通过革兰氏阴性病原体，例如铜绿假单胞菌。抗生素抗性的速率增加 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 可以通过使用交替的磁性来实现生物膜在金属植入物上的处理 字段（AMF）。当金属假体暴露于AMF时，在其表面诱导电流， 导致快速加热会破坏生物膜。这种治疗方法非常有效地杀死 生物膜的细菌成分，可与传统抗菌剂一起使用以实现 完全治疗感染。研究小组假设集中于体内金属的加热 通过递送AMF的植入物表面将是嵌入附着的病原体的杀菌性 生物膜将增加对抗菌剂的敏感性，并在体内安全。总体目标 研究是为了通过AMF暴露在大小动物模型中通过AMF暴露来评估生物膜的消除 植入物感染，以及设计和表征适合治疗人类的原型AMF设备 植入物感染。该建议旨在回答有关最佳功率，温度， 以及既安全又有效的总曝光时间。这将代表 能够原位治疗植入物，避免数百万的手术和相应的数十亿美元 和他们在一起。