Implant Biofilm Mediated Immune Response

项目总结 这是一项来自早期研究人员的建议，旨在解决宿主生物膜的机制基础。 外科植入物相关并发症的相互作用。据估计，有1000万女性 全世界，包括300万美国人做了隆胸手术。超过700万美国人生活在髋关节/膝盖植入物中。在美国，每年有近30万名女性接受隆胸手术，原因包括乳房切除后的乳房重建(乳腺癌和预防性乳房切除)， 增强/重建、美容增强和性别肯定。超过100万人的髋关节和总 在美国，每年都会进行膝关节置换手术。随着人口老龄化，对 提高机动性和生活质量。关节置换手术的数量预计将增加 在未来相当长的时间里。全关节置换手术预计将继续是最常见的手术之一 在接下来的几十年里进行选择性外科手术。 有越来越多的患者经历了一系列与他们的 植入物。所描述的症状包括肌痛、慢性疲劳、结缔组织疾病和许多 其他通常与自身免疫性疾病相关的表现。在隆胸的情况下，这些星座 一种免疫症状被称为乳房植入性疾病(BII)。据报道，受试者也出现了类似的症状。 用整形外科植入物。用于关节成形术的金属/塑料植入物和用于乳房的硅胶植入物由 不同的材料。因此，这些情况的根本原因可能与其他因素有关 植入材料。细菌生物膜是外科植入物失败、感染和 翻修手术。尽管在手术期间努力保持无菌状态，但植入式医疗设备可能会成为 被寄主微生物区系中的机会性细菌污染，其中许多会形成生物膜。 这项建议旨在调查细菌生物膜在种植体相关疾病中的作用。宿主-生物被膜 相互作用是由生物膜所在宿主的局部微环境引导的。乳房和臀部 关节置换物有一个宿主-微环境，其中含有丰富的脂肪组织，包括脂质。该提案旨在 研究生物膜-宿主相互作用过程中形成的脂质代谢物。我们假设一种脂质代谢物形成于 以生物膜名为(E)-10-羟基-8-十八碳烯酸(10-home)可刺激CD4T细胞导致 自身免疫样症候群。代谢物10-Home是生物膜作用于宿主形成的氧磷脂的一员 油酸。氧化脂质是由脂肪酸通过依赖于氧气的反应形成的氧化脂质 氧化。据报道，奥昔利平有助于炎症反应。该提案的基础是 来自患者样本的初步数据，使用体外和体内动物模型进行了广泛的研究，以 了解在氧化脂质存在的情况下CD4Th1亚型激活的机制 宿主-生物膜相互作用。

PROJECT SUMMARY This is a proposal from early-stage investigator to address the mechanistic underpinnings of host-biofilm interaction in the context of surgical implant-associated complications. It is estimated 10 million women worldwide, including 3 million Americans have breast implants. Over 7 million Americans are living with hip/knee implants. Nearly 300,000 women annually have breast implant surgery in the United States, for reasons including post-mastectomy breast reconstruction (breast cancer and prophylactic mastectomy), revision of prior augmentation/ reconstruction, cosmetic augmentation, and gender affirmation. Over 1 million total hip and total knee replacement surgeries are performed each year in the US. With an aging population, there is a demand for improved mobility and quality of life. The number of joint replacement surgeries are projected to increase considerably in the future. Total joint replacement surgery is expected to continue to be one of the most common elective surgical procedures in the coming decades. There has been increased identification of patients experiencing a constellation of symptoms related to their implants. The symptoms described include myalgias, chronic fatigue, connective-tissue disorders, and a host of other manifestations often associated with autoimmune illnesses. In case of breast implants, these constellations of immune symptoms are named Breast Implant Illness (BII). Similar symptoms have been reported in subjects with orthopedic implants. Metal/plastic implants for arthroplasty and silicone implants for breasts are made of different materials. Thus, the underlying cause of these conditions may be associated with factors other than the implant material. Bacterial biofilms are one of the leading causes of surgical implant failures, infection and revision surgeries. Despite efforts to maintain sterility during surgery, implantable medical devices can become contaminated with the opportunistic bacteria from the host microflora many of which can form biofilm. This proposal aims to investigate the role of bacterial biofilms in the implant-associated illness. Host-biofilm interactions are guided by the local micro-environmental niche of host in which the biofilm reside. Breast and hip joint replacements have a host-microenvironment rich in adipose tissue comprising lipids. The proposal aims to study lipid metabolites formed during biofilm-host interaction. We hypothesize that a lipid metabolite formed due to biofilm called (E)-10-hydroxy-8-octadecenoic acid (10-HOME) can stimulate CD4+ T cell leading to autoimmune-like syndromes. The metabolite 10- HOME is a member of oxylipin formed by biofilm acting on host oleic acid. Oxylipins are oxidized lipids formed from fatty acids by reactions involving dioxygen-dependent oxidation. Oxilipins have been reported to contribute to inflammatory response. The proposal is based on preliminary data derived from patient samples, studied extensively using in vitro and in vivo animal models to understand the mechanistic pathway of CD4+ Th1 subtype activation in presence of oxylipins derived due to host-biofilm interaction.