Periodontal Biomaterials with BITE (Biofilm Immunity via T-cell Enhancement)

具有 BITE（通过 T 细胞增强的生物膜免疫）的牙周生物材料

基本信息

批准号：
7673964
负责人：
James D. Bryers
金额：
$ 36.64万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-15 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7673964
关键词：
Adjuvant Adult Affect Aftercare Alveolar Bone Loss American Anti-Bacterial Agents Antibiotic Resistance Antibiotic Therapy Antibiotics Antibodies Antibody Formation Antigen Presentation Antigen Receptors Antigen-Presenting Cells Antigens B-Cell Activation B-Lymphocytes Bacteria Bacterial Adhesins Bacterial Endocarditis Bacterial Infections Binding Biocompatible Materials Biological Biomedical Engineering Cardiovascular system Catheters Cause of Death Cell Count Cell surface Cells Centers for Disease Control and Prevention (U.S.)Cessation of life Chimeric Proteins Chronic Code Complex Contact Lenses Cornea Coupled Coupling Cystic Fibrosis Defect Dendritic Cells Dental Dental Implants Dental caries Development Device Removal Devices Disease Encapsulated Engineering Enterococcus faecalis Epidemic Escherichia coli Exhibits Exposure to Failure Fc Receptor Fibronectins Figs - dietary Generic Drugs Glycolipids Goals Gram-Negative Bacteria Growth Guided Tissue Regeneration Healed Heart Valves Hemorrhage Hospitals Human Immune response Immunity Immunization Implant Implantation procedure In Vitro Individual Infection Infection prevention Inflammation Inflammatory Injection of therapeutic agent Life Ligands Lung Mammalian Cell Mannose Measures Medical Medical Device Membrane Memory B-Lymphocyte Messenger RNA Microbial Biofilms Microspheres Modeling Monoclonal Antibodies Movement Mus National Institute of Dental and Craniofacial Research Nosocomial Infections Operative Surgical Procedures Opsonin Organism Particulate Patients Peptide Hydrolases Periodontal Diseases Periodontal Guided Tissue Regeneration Periodontal Pocket Periodontitis Phagocytosis Play Polymers Population Porphyromonas gingivalis Process Property Pseudomonas aeruginosa Public Health Reporting Resistance development Risk Role Series Severity of illness Site Societies Staphylococcus aureus Staphylococcus epidermidis Streptococcus Group B Streptococcus mutans Surface System T-Lymphocyte Techniques Technology Time Tissue Model Tissues Tooth Loss Tooth Tissue Transfection Urinary tract infection Vaccinated Vaccine Design Vaccines Work Wound Healing alveolar bone antimicrobial base biodegradable polymer cost design ear infection healing implantation in vivo killer T cell killings macrophage microbial microorganism middle ear monocyte monomer nanoparticle novel oral bacteria particle pathogen premature prevent protein complex public health relevance receptor reconstruction regenerative response scaffold scaling and root planing stressor success tissue regeneration trafficking uptake vector

项目摘要

DESCRIPTION (provided by applicant): Biofilms are thought to cause a significant amount of all human microbial infections, according to the Centers for Disease Control and Prevention [1]. Nosocomial infections are the fourth leading cause of death in the U.S. with >2 million cases annually (or ~10% of American hospital patients). About 60% of all such infections are associated with an implanted medical device causing >$4.5 billion medical costs in 1992 [2] and ~80,000 deaths annually [3]. Well-recognized infections involving biofilms include bacterial endocarditis, cystic fibrosis lung infections, deep wound healing, the current dental caries epidemic, periodontal disease, vaginosis, urinary tract infections, and chronic middle ear infections. Chronic periodontitis is an inflammatory disease of the supporting tissues of the teeth leading to resorption of alveolar bone and eventual tooth loss. The disease is a major public health problem in all societies and is estimated to affect up to 15% of the adult dentate population, with severe forms affecting 5 6%. The development and progression of chronic periodontitis has been associated with specific Gram-negative bacteria in subgingival plaque. Persistence of Porphyromonas gingivalis in subgingival plaque from periodontitis patients after treatment (scaling and root planing) has been reported to be significantly associated with progressive alveolar bone loss. Moreover, an increase in P. gingivalis cell numbers in subgingival plaque has been shown to correlate with disease severity as measured by attachment loss, periodontal pocket depth, and bleeding on probing. Guided tissue regeneration (GTR) techniques are increasingly being used for the treatment of periodontal defects, or in conjunction with dental implant procedures. Several studies have shown that optimal tissue regeneration cannot be expected for barrier membranes placed in sites infected by periodontopathic microorganisms. A prerequisite for tissue regeneration success is therefore an infection-free healing process. This proposal seeks to develop biomaterials that promote a life-long immunity protection against infections of long-term indwelling biomedical devices. Our goal, with NIDCR support, is to develop tissue regenerative biomaterials that will also provide a short- term defense and long-term immune response to specific bacterial colonization. For short-term immediate defense, model biomaterials will release fusion protein complexes - artificial opsonins - designed to enhance the coupling of pathogenic oral bacteria to monocyte-macrophage (MX); thus promoting phagocytosis. For long-term protection, the biomaterial will transfect antigen-presenting cells (specifically dendritic cells - DCs) to produce T- and B-cell memory and antibody expression, and potentially stimulate direct native killer T-cell responses. This two-tiered biological approach to preventing biomaterials infections will first be established in the model microbial system of Porphyromonas gingivalis (PG) colonization of periodontal tissue guided regeneration systems. PUBLIC HEALTH RELEVANCE: Nosocomial infections are the fourth leading cause of death in the U.S. with ~60% of such infections being associated with an implanted medical device. Our goal is to develop tissue regenerative biomaterials that will also provide a short-term defense and life long immune response to specific bacterial infections

描述（由申请人提供）：根据疾病控制和预防中心的说法，认为生物膜会引起大量的所有人类微生物感染[1]。医院感染是美国第四大死亡原因，每年约200万例（约占美国医院患者的10％）。在所有此类感染中，约有60％与植入的医疗装置有关，1992年造成45亿美元的医疗费用[2]和约80,000例死亡[3]。公认的涉及生物膜的感染包括细菌性心内膜炎，囊性纤维化肺部感染，深伤，当前的龋齿流行，牙周疾病，阴道病，尿路感染和慢性中耳感染。慢性牙周炎是牙齿支撑组织的一种炎症性疾病，导致肺泡骨和最终牙齿脱落。该疾病是所有社会的主要公共卫生问题，据估计会影响多达15％的成人牙齿人群，严重形式影响5 6％。慢性牙周炎的发育和进展与尺寸斑块中的特定革兰氏阴性细菌有关。据报道，牙周炎患者的牙龈牙龈牙龈牙龈（牙周牙菌斑（缩放和根平行））的持久性与进行性肺泡骨质流失显着相关。此外，已显示牙龈牙周牙疟原虫细胞数量的增加与疾病的严重程度相关，如通过固定损失，牙周口袋深度和探测时出血而衡量。引导组织再生（GTR）技术越来越多地用于治疗牙周缺陷或与牙科植入程序结合使用。几项研究表明，对于放置在受牙周病微生物感染的部位的屏障膜而言，无法期望最佳组织再生。因此，组织再生成功的先决条件是无感染的愈合过程。该建议旨在开发生物材料，以促进针对长期留置生物医学手段感染的终身免疫力保护。在NIDCR支持的情况下，我们的目标是开发组织再生生物材料，该生物材料还将提供短期防御和对特定细菌定植的长期免疫反应。对于短期立即防御，模型生物材料将释放融合蛋白复合物 - 人造opsonins-旨在增强致病性口服细菌与单核细胞巨噬细胞（MX）的偶联；从而促进吞噬作用。为了长期保护，生物材料将转染抗原呈递细胞（特异性树突状细胞-DC），以产生T-和B细胞记忆和抗体表达，并可能刺激直接的天然杀手T细胞反应。这种预防生物材料感染的两层生物学方法将首先在模型的牙龈卟啉单胞菌（PG）牙周组织引导再生系统的微生物系统中建立。公共卫生相关性：医院感染是美国的第四大死亡原因，其中约60％的此类感染与植入的医疗装置有关。我们的目标是开发组织再生生物材料，该生物材料还将为特定细菌感染提供短期防御和寿命长期的免疫反应