Implant Biofilm Mediated Immune Response

植入物生物膜介导的免疫反应

• 批准号: 10587141
• 负责人: Mithun Sinha
• 金额: $ 30.78万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10587141
• 关键词: Address; Adherence; Adipose tissue; American; Animal Model; Applications Grants; Autoimmune; Bacteria; Biological; Biological Specimen Banks; Breast; CD4 Positive T Lymphocytes; Chronic; Clinical Research; Collagen; Connective Tissue Diseases; Cosmetics; Data; Dioxygen; Elective Surgical Procedures; Failure; Fatigue; Fatty Acids; Foundations; Future; Gender; Growth; Hip region structure; Human; Immune; Immune response; Immunologist; Immunomodulators; Implant; In Vitro; Infection; Inflammatory Response; Internal Breast Prosthesis; Knee; Laboratories; Life Expectancy; Link; Lipids; Mammaplasty; Mammary Gland Parenchyma; Mastectomy; Mediating; Medical Device; Metals; Microbial Biofilms; Modeling; Molecular; Mus; Myalgia; Names; National Institute of Allergy and Infectious Disease; Octadecenoic Acids; Oleic Acids; Operative Surgical Procedures; Oral cavity; Orthopedics; Pathway interactions; Patients; Persons; Plastic Surgeon; Polymers; Prevalence; Prognosis; Prosthesis; Publications; Quality of life; Reaction; Replacement Arthroplasty; Reporter; Reporting; Research; Research Design; Research Personnel; Role; Sampling; Sampling Studies; Seeds; Silicones; Sterility; Surface; Surgeon; Symptoms; Syndrome; T-Cell Activation; T-Lymphocyte; Testing; Texture; Th1 Cells; Tissues; United States; United States Food and Drug Administration; United States National Institutes of Health; Woman; Work; aging population; base; capsule; career; experience; eye dryness; hip replacement arthroplasty; host microbiota; immunoreaction; immunoregulation; implant material; improved mobility; in vivo; knee replacement arthroplasty; malignant breast neoplasm; member; microbial; oxidation; oxidized lipid; peripheral blood; programs; prophylactic mastectomy; reconstruction; response; transcription factor

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.

项目概要 这是早期研究人员提出的一项提案，旨在解决宿主生物膜的机制基础 手术植入相关并发症中的相互作用。据估计有1000万女性 在全世界范围内，包括 300 万美国人进行了隆胸手术。超过 700 万美国人佩戴髋关节/膝关节植入物。在美国，每年有近 300,000 名女性接受乳房植入手术，原因包括乳房切除术后乳房重建（乳腺癌和预防性乳房切除术）、之前乳房切除术的修正 增强/重建、美容增强和性别肯定。超过 100 万个总髋关节和总 美国每年都会进行膝关节置换手术。随着人口老龄化，需求 改善流动性和生活质量。关节置换手术的数量预计将增加 未来相当大。全关节置换手术预计将继续成为最常见的手术之一 未来几十年的选择性外科手术。 越来越多的患者出现与其自身相关的一系列症状。 植入物。所描述的症状包括肌痛、慢性疲劳、结缔组织疾病以及一系列 其他表现通常与自身免疫性疾病有关。如果是隆胸，这些星座 的免疫症状被称为乳房植入病（BII）。受试者中也报告了类似的症状 与骨科植入物。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以下材料制成 不同的材料。因此，这些情况的根本原因可能与以下因素有关： 植入材料。细菌生物膜是手术植入物失败、感染和感染的主要原因之一。 翻修手术。尽管在手术期间努力保持无菌，但植入式医疗设备可能会变得 被宿主微生物区系的机会性细菌污染，其中许多细菌可以形成生物膜。 该提案旨在研究细菌生物膜在植入相关疾病中的作用。宿主生物膜 相互作用是由生物膜所在宿主的局部微环境生态位引导的。胸部和臀部 关节置换物具有富含含有脂质的脂肪组织的宿主微环境。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。我们假设脂质代谢物的形成是由于 称为 (E)-10-羟基-8-十八碳烯酸 (10-HOME) 的生物膜可以刺激 CD4+ T 细胞，从而导致 自身免疫样综合征。代谢物10-HOME是生物膜作用于宿主形成的氧脂素的成员 油酸。氧脂质是由脂肪酸通过涉及双氧依赖性反应形成的氧化脂质 氧化。据报道，Oxilipins 有助于炎症反应。该提案基于 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研究 了解在衍生自 oxylipins 的情况下 CD4+ Th1 亚型激活的机制途径 宿主-生物膜相互作用。