Implant Biofilm Mediated Immune Response

植入物生物膜介导的免疫反应

• 批准号: 10707355
• 负责人: Mithun Sinha
• 金额: $ 31.21万
• 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/10707355
• 关键词: Address; Adherence; Adipose tissue; American; Animal Model; Applications Grants; Autoimmune; Bacteria; Biological; Biological Specimen Banks; Breast; CD4 Positive T Lymphocytes; Chronic; Collagen; Connective Tissue Diseases; Cosmetics; Data; Dioxygen; Elective Surgical Procedures; Failure; Fatigue; Fatty Acids; Foundations; Future; Growth; Hip region structure; Home; Immune; Immune response; Immunologist; Immunomodulators; Implant; In Vitro; Infection; Inflammation; 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; Pathogenesis; Pathway interactions; Patients; Persons; Plastic Surgeon; Polymers; Prevalence; Prognosis; Publications; Quality of life; Reaction; Replacement Arthroplasty; Reporter; Reporting; Research; Research Personnel; Role; Sampling; Second Look Surgery; Silicones; Sterility; Surface; Surgeon; Symptoms; Syndrome; T-Cell Activation; Testing; Texture; Th1 Cells; Tissues; United States; United States Food and Drug Administration; United States National Institutes of Health; Woman; Work; aging population; capsule; career; experience; eye dryness; gender affirmation; hip replacement arthroplasty; host microbiota; immunoreaction; implant material; implantable device; improved mobility; in vivo; knee replacement arthroplasty; malignant breast neoplasm; medical implant; member; microbial; oxidation; oxidized lipid; pathogenic bacteria; 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.

项目摘要 这是早期研究人员的提议，要解决宿主双膜的机械基础 在手术植入物相关并发症的背景下相互作用。估计有1000万妇女 全球，包括300万美国人有乳房植入物。超过700万美国人生活在臀部/膝盖植入物中。由于包括乳腺切除术后乳房重建（乳腺癌和预防性乳房切除术）的原因 增强/重建，化妆品增强和性别肯定。超过100万的臀部和总数 每年在美国进行膝盖置换手术。人口老龄化，需要 改善流动性和生活质量。预计关节置换手术的数量将增加 将来相当大。预计全部关节置换手术将继续是最常见的 在未来几十年中，选修手术程序。 人们对患者的症状相关的症状已有增加 植入物。描述的症状包括肌痛，慢性疲劳，结缔组织疾病和许多 其他表现通常与自身免疫性疾病有关。如果乳房植入物，这些星座 免疫症状称为乳房植入疾病（BII）。受试者已经报道了类似的症状 与骨科植入物。用于关节置换术的金属/塑料植入物和乳房的硅酮植入物由 不同的材料。因此，这些条件的根本原因可能与其他因素有关 植入物材料。细菌生物膜是手术植入物失败，感染和 修订手术。尽管在手术过程中努力保持不育，但可植入的医疗设备仍可以成为 受宿主微生物的机会性细菌污染，其中许多可以形成生物膜。 该建议旨在研究细菌生物膜在植入物相关疾病中的作用。寄主 - 膜 相互作用由生物膜驻留的局部宿主的局部微环境利基领域指导。乳房和臀部 关节置换具有富含脂肪组织的宿主微环境，其中包括脂质。该提议旨在 研究在生物膜宿主相互作用期间形成的脂质代谢产物。我们假设形成了脂质代谢物 称为（E）-10-羟基-8-二十二烯酸（10家居）的生物膜可以刺激CD4+ T细胞，导致 自身免疫性综合征。代谢物10-家居是作用于宿主的生物膜形成的氧蛋白的成员 油酸。油磷脂是由涉及二恶英依赖性的反应形成的氧化脂质 氧化。据报道，氧化肽有助于炎症反应。该提议基于 从患者样本中得出的初步数据，使用体外和体内动物模型进行了广泛的研究 了解在存在由于衍生物而导致的氧基蛋白存在下，CD4+ Th1亚型激活的机械途径 宿主双膜相互作用。