Novel Biofilm Paradigm Explaining Clinical Implant-Associated Illness.

解释临床植入相关疾病的新型生物膜范式。

基本信息

批准号：
10629428
负责人：
Mithun Sinha
金额：
$ 19.81万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-26 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10629428
关键词：
Address Adherence Adhesions Adipose tissue American Animal Model Autoimmune Autoimmune Responses Autoimmunity Bacteria Biological Biological Specimen Banks Breast CD4 Positive T Lymphocytes Chronic Clinical Collagen Connective Tissue Diseases Cosmetics Data Dental Implants Dioxygen Elective Surgical Procedures Exhibits Failure Fatigue Fatty Acids Foreign Bodies Future Growth Hip region structure Home Immune Immune response Immunologist Implant Infection Inflammation Inflammatory Response Internal Breast Prosthesis Investigation Knee Laboratories Life Expectancy Link Lipids Mammaplasty Mastectomy Mediating Medical Device Metals Microbial Biofilms Mus Myalgia National Institute of Allergy and Infectious Disease Octadecenoic Acids Operative Surgical Procedures Orthopedics Patients Persons Plastic Surgeon Prevalence Quality of life Reaction Replacement Arthroplasty Reporter Reporting Research Personnel Role Sampling Second Look Surgery Silicones Site Sterility Surface Surgeon Symptoms Syndrome Testing Texture Th1 Cells Tissues United States United States Food and Drug Administration United States National Institutes of Health Woman Work aging population animal data capsule enzyme activity experience gender affirmation hip replacement arthroplasty host microbiota immune activation immunogenic immunoreaction implant material implantable device improved mobility knee replacement arthroplasty malignant breast neoplasm medical implant novel oxidation oxidized lipid pathogenic bacteria prophylactic mastectomy prospective reconstruction response transcription factor

项目摘要

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.

项目概要这是一名研究人员提出的一项提案，旨在解决宿主与生物膜相互作用的机制基础。手术植入相关并发症的背景。据估计，全世界有 1000 万女性，其中包括 300 万美国人接受了隆胸手术。超过 700 万美国人佩戴髋关节/膝关节植入物。几乎在美国，每年有 300,000 名女性接受乳房植入手术，原因包括术后乳房切除术乳房重建（乳腺癌和预防性乳房切除术），先前隆胸的修正/ 重建、美容增强和性别肯定。超过 100 万髋关节和膝关节总量美国每年都会进行置换手术。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。用于关节置换术的金属/塑料植入物和乳房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因素有关。细菌生物膜是细菌生物膜的主要原因之一外科植入物失败、感染和翻修手术。尽管在手术期间努力保持无菌，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。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（氧脂质）。氧脂质是氧化脂质，由通过涉及双氧依赖性氧化的反应来产生脂肪酸。据报道，氧脂质有助于炎症反应。我们假设生物膜形成的氧脂质可以刺激 CD4+ T 细胞引导自身免疫样综合征。