Plasma-based therapies for bone infection: A tripartite USA/Northern Ireland/Republic of Ireland consortium

摘要 骨科感染危及生命，目前的治疗方法仅有少量成功。尽管 积极的围手术期抗生素治疗，膝关节矫正的1.5%，脊柱感染的0.7%至11.9% (取决于手术的复杂程度)，多达27%的开放性骨折会受到感染。此外， 组织与易被生物膜的矫形器械接口的复杂性使细菌复杂化。 根除使得目前的治疗时间更长、费用更高。为了解决这一严重问题，我们建议 使用冷血浆和冷等离子体活化液(PAL)对抗感染。我们的试点数据显示，这些 可以为高杀菌活性与免疫刺激特性相结合的新方法量身定做 没有抗生素耐药性的风险。重要的是，这些方法还没有被用于抗击骨骼。 感染。为了利用这项技术来解决骨科感染问题，一个由国际社会组成的三方联盟 来自美国、爱尔兰共和国和北爱尔兰的冷等离子体技术前沿的研究团队 爱尔兰已经集结。这个联盟联合了等离子工程、微生物学、材料 科学、化学、细胞生物学和临床医学。有三个具体目标。(1)确定 直接冷等离子体处理对耐甲氧西林金黄色葡萄球菌生物被膜和免疫细胞反应的影响 血浆活化液(PAL)单独及与直接冷联合应用的作用机制和疗效 等离子体治疗根除感染；以及(3)通过冷等离子体和PAL相结合来解决感染 感染截骨的临床相关动物模型的治疗。我们将开发冷等离子体和PAL 直接破坏生物膜并根除细菌，同时刺激免疫反应的治疗方法。在… 在这项研究的最后，我们将制定一种简单有效的非抗生素治疗方案来治愈 手术部位感染通过联合免疫激活和直接根除细菌。临床上，这是一种 冷等离子体+PAL治疗方案可以与现有的临床方案无缝集成，以增强 并最终取代我们对抗生素疗法的依赖。

ABSTRACT Orthopaedic infection is life-threatening and current treatments are only sparingly successful. Despite aggressive peri-operative antibiotic treatments, 1.5% of knee revisions, 0.7 to 11.9%, of spinal infections (depending on the complexity of the procedure) and up to 27% of open fractures become infected. Moreover, the complexity of tissues interfacing with the biofilm-prone orthopaedic instrumentation complicates bacterial eradication making current treatments prolonged and expensive. To address this serious issue, we propose to combat the infection using cold plasma and cold plasma activated liquid (PAL). Our pilot data show that these novel modalities can be tailored for high microbicidal activity coupled with immune stimulatory properties without the risk of antibiotic resistance. Importantly, these modalities have not been used to combat bone infections. To utilize this technology to address orthopaedic infection, a tri-partite consortium of international research teams at the forefront of cold plasma technology from the US, the Republic of Ireland and Northern Ireland have been assembled. This consortium unites expertise in plasma engineering, microbiology, material science, chemistry, cell biology, and clinical medicine. There are three Specific Aims. (1) To determine the effect of direct cold plasma treatment on MRSA biofilms and immune cell response; (2) To determine the mechanisms of action, and efficacy of Plasma Activated Liquid (PAL) alone and in combination with direct cold plasma treatment to eradicate infection; and (3) To resolve infection through combined cold plasma and PAL treatments in a clinically relevant animal model of infected osteotomy. We will develop cold plasma and PAL treatments that will directly disrupt biofilms and eradicate bacteria while stimulating the immune response. At the end of this study, we will have developed a simple and effective non-antibiotic treatment protocol to cure surgical site infection through combined immune activation and direct eradication of bacteria. Clinically, this cold plasma+PAL treatment protocol can be seamlessly integrated with existing clinical protocols to enhance and eventually replace our reliance on antibiotic therapies.