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：
8274339
负责人：
James D. Bryers
金额：
$ 40.51万
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 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8274339
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 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 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 cell response 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 disorder prevention 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，生物膜被认为是导致大量人类微生物感染的原因[1]。医院感染是美国第四大死亡原因，每年有超过 200 万例病例（约占美国医院患者的 10%）。所有此类感染中约 60% 与植入医疗设备有关，1992 年造成的医疗费用超过 45 亿美元[2]，每年约有 80,000 人死亡[3]。众所周知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、深层伤口愈合、当前的龋齿流行、牙周病、阴道病、尿路感染和慢性中耳感染。慢性牙周炎是牙齿支持组织的炎症性疾病，导致牙槽骨吸收并最终导致牙齿脱落。该疾病是所有社会的一个主要公共卫生问题，估计影响高达 15% 的成年人齿状人口，其中严重形式影响 5-6%。慢性牙周炎的发生和进展与龈下菌斑中的特定革兰氏阴性菌有关。据报道，牙周炎患者治疗（洗牙和根面平整）后龈下菌斑中牙龈卟啉单胞菌的持续存在与进行性牙槽骨流失显着相关。此外，龈下菌斑中牙龈卟啉单胞菌细胞数量的增加已被证明与通过附着丧失、牙周袋深度和探诊出血来衡量的疾病严重程度相关。引导组织再生（GTR）技术越来越多地用于治疗牙周缺损，或与牙种植手术结合使用。多项研究表明，对于放置在牙周病微生物感染部位的屏障膜来说，不能期望获得最佳的组织再生。因此，组织再生成功的先决条件是无感染的愈合过程。该提案旨在开发生物材料，以促进终身免疫保护，防止长期留置生物医学设备的感染。在 NIDCR 的支持下，我们的目标是开发组织再生生物材料，该材料还将针对特定细菌定植提供短期防御和长期免疫反应。为了实现短期即时防御，模型生物材料将释放融合蛋白复合物——人工调理素——旨在增强致病性口腔细菌与单核巨噬细胞（MX）的偶联；从而促进吞噬作用。为了实现长期保护，生物材料将转染抗原呈递细胞（特别是树突状细胞 - DC）以产生 T 细胞和 B 细胞记忆和抗体表达，并可能刺激直接的天然杀伤 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牙周组织引导再生系统的牙龈卟啉单胞菌（PG）定植的模型微生物系统中建立。公共卫生相关性：医院感染是美国第四大死亡原因，其中约 60% 的感染与植入医疗设备有关。我们的目标是开发组织再生生物材料，该材料还将针对特定细菌感染提供短期防御和终生免疫反应