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

摘要 骨科感染是危及生命的，目前的治疗方法只有很少的成功。尽管 积极的围手术期抗生素治疗，1.5%的膝关节翻修，0.7 - 11.9%的脊柱感染 （取决于手术的复杂性），高达27%的开放性骨折会感染。此外，委员会认为， 与易形成生物膜的骨科器械接触的组织的复杂性使得细菌感染 根除使得目前的治疗延长且昂贵。为了解决这一严重问题，我们建议 使用冷等离子体和冷等离子体激活液（PAL）对抗感染。我们的试点数据显示，这些 新的模式可以被定制为具有高杀微生物活性和免疫刺激特性 而不会产生抗生素耐药性。重要的是，这些方式尚未用于对抗骨 感染.为了利用这项技术来解决骨科感染，一个国际三方联盟， 来自美国、爱尔兰共和国和北方的冷等离子体技术前沿的研究团队 爱尔兰已经集结完毕。该联盟联合了等离子体工程、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MRSA生物膜和免疫细胞应答的影响;（2）确定 血浆激活液（PAL）单独使用和与直接感冒联合使用的作用机制和疗效 等离子体治疗以根除感染;（3）通过冷等离子体和PAL的组合来解决感染 在感染性截骨术的临床相关动物模型中进行治疗。我们将开发冷等离子体和PAL 这些治疗将直接破坏生物膜并根除细菌，同时刺激免疫反应。在 本研究结束时，我们将制定一个简单有效的非抗生素治疗方案，以治愈 通过联合免疫激活和直接根除细菌来预防手术部位感染。临床上，这 冷等离子体+PAL治疗方案可以与现有的临床方案无缝集成， 并最终取代我们对抗生素治疗的依赖。

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.