Novel Biofilm Paradigm Explaining Clinical Implant-Associated Illness.

项目摘要 这是一个研究者的建议，目的是解决宿主-生物膜相互作用的机制基础， 外科植入物相关并发症的背景。据估计，全世界有1000万妇女， 300万美国人隆胸超过700万美国人生活在髋关节/膝关节植入物中。近 在美国，每年有30万名妇女接受乳房植入手术，原因包括术后 乳房切除术乳房再造（乳腺癌和预防性乳房切除术），既往隆乳翻修术/ 整形美容和性别确认超过100万个全髋关节和全膝关节 在美国，每年都会进行置换手术。随着人口老龄化， 改善流动性和生活质量。关节置换手术的数量预计将增加 在未来相当大的。全关节置换手术预计将继续成为最常见的手术之一。 在未来几十年里，选择性外科手术。 已经有越来越多的识别患者经历的一系列症状相关的， 植入物.所描述的症状包括肌痛、慢性疲劳、结缔组织疾病和一系列 其他表现往往与自身免疫性疾病。用于关节成形术的金属/塑料植入物， 用于乳房的硅胶植入物由不同的材料制成。因此，这些情况的根本原因可能 与植入物材料以外的因素有关。细菌生物膜是导致 外科植入物失效、感染和翻修手术。尽管在手术过程中努力保持无菌， 可植入的医疗装置可能被来自宿主微生物群落的机会性细菌污染 其中许多可形成生物膜。 该提案旨在研究细菌生物膜在植入物相关疾病中的作用。寄主生物膜 相互作用是由生物膜所在的宿主的局部微环境生态位引导的。乳房和臀部 关节置换物具有富含包含脂质的脂肪组织的宿主微环境。这项建议旨在 研究脂质代谢产物（氧化脂质）在生物膜-宿主相互作用过程中形成。氧化脂质是氧化脂质， 脂肪酸通过涉及双氧依赖性氧化的反应。据报道，氧脂素有助于 炎症反应。我们假设，由于生物膜形成的氧脂素可以刺激CD 4 + T细胞， 自身免疫样综合征。

PROJECT SUMMARY This is a proposal from an 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. 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 (oxylipins) formed during biofilm-host interaction. Oxylipins are oxidized lipids formed from fatty acids by reactions involving dioxygen-dependent oxidation. Oxylipins have been reported to contribute to inflammatory response. We hypothesize that oxylipins formed due to biofilm can stimulate CD4+ T cell leading to autoimmune-like syndromes.