Novel Biofilm Paradigm Explaining Clinical Implant-Associated Illness.

项目总结 这是一位研究人员提出的一项提案，旨在解决宿主-生物膜相互作用的机制基础。 手术植入物相关并发症的背景。据估计，全世界有1000万女性，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。差一点 在美国，每年有30万女性接受隆胸手术，原因包括术后 乳房切除乳房重建术(乳腺癌和预防性乳房切除术)，修订以前的隆乳术/ 重建、整容和性别肯定。超过100万的全髋关节和全膝关节 在美国，每年都会进行替代手术。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。金属/塑料植入物用于关节成形术和 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是 与植入材料以外的其他因素有关。细菌生物膜是引起肺炎的主要原因之一 外科植入失败、感染和翻修手术。尽管在手术期间努力保持无菌状态， 植入式医疗设备可能会被宿主微生物群中的机会细菌污染。 其中许多可以形成生物膜。 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 研究生物膜与宿主相互作用过程中形成的脂类代谢产物(氧合脂)。氧磷脂是氧化的脂类，由 通过涉及依赖于氧的氧化反应的脂肪酸。据报道，氧磷脂有助于 炎症反应。我们推测生物膜形成的氧化脂质可以刺激CD4T细胞引导 与自身免疫性综合症有关。

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.