Healing Chronic Wounds by Controlling Microbial Biofilm

通过控制微生物生物膜治愈慢性伤口

基本信息

批准号：
7492526
负责人：
PHILIP S STEWART
金额：
$ 0.14万
依托单位：
MONTANA STATE UNIVERSITY - BOZEMAN
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7492526
关键词：
Acute Address Animals Antibiotics Architecture Biological Models Cells Chronic Clinic Clinical Communities Cultured Cells Decubitus ulcer Dermatologist Diabetic Foot Ulcer Diabetic ulcer Disease Endocarditis Engineering Excision Gallium Goals Healed Health Expenditures Host Defense Human Image In Vitro Infection Iron Knowledge Laboratories Lactoferrin Lead Leg Ulcer Marriage Methods Microbial Biofilms Microbiology Modeling Morbidity - disease rate Mus Organ Culture Techniques Organism Osteomyelitis Otitis Media Oxygen Pathway interactions Patients Phase I Clinical Trials Polymers Polysaccharides Research Research Personnel Ribosomal RNA Risk Safety Sampling Science Signal Transduction Simulate Sinusitis Source Specimen Standards of Weights and Measures Stasis Ulcer Structure System Techniques Technology Testing Tissues Ulcer Ultrasonography Universities Venous Washington Work Wound Healing Wound Infection base concept extracellular healing improved in vivo in vivo Model innovation keratinocyte killings microbial community microorganism model development mortality mouse model multidisciplinary novel strategies prevent prostatitis quorum sensing success tissue culture wound

项目摘要

This project will address the hypothesis that poor healing of many chronic wounds is due to the formation of infectious microbial biofilms. Biofilms are known to form preferentially on dead or damaged tissue and contribute to peristence because microorganisms in biofilms evade killling by antibiotics and by the host defenses. A corollary of the hypothesis is that therapies that effectively target microbial biofilms will improve healing of these wounds. The goal of this project is to develop knowledge and techniques needed to evaluate the potential utility of anti-biofilm therapies in the context of wound healing. This will be accomplished by characterizing the presence, speciation, structure, arid oxygen availability in wound biofilms (Aim #1), developing a suite of in vitro and in vivo models of chronic wound biofilm infection that simulate diverse aspects of biofilms in wounds (Aim #2), and applying these models to evaluate the efficacy and safety of several potential anti-biofilm technologies (Aim #3). The models include polymicrobial biofilms grown in laboratory systems, a keratinocyte scratch model interfaced with bacterial biofilm, a rafted organ culture model, and mouse models of chronic wound infection. Success in this project depends on merging expertise from biofilm science and technology with expertise in wound healing and therefore requires a multidisciplinary team of biofilm microbiologists and engineers, dermatologists, cell biologists, and clinical collaborators. The project is innovative and high-risk in three important respects. This project involves investing in the biofilm concept by bringing in investigators who are outside the wound healing community. The marriage of microbial biofilm to tissue culture and animal wound models is innovative. And finally, some of the proposed anti-biofilm strategies are clearly high-risk. Wounds that fail to heal, such as diabetic foot ulcers, venous leg ulcers, and pressure ulcers are a major source of morbidity, mortality, and health care expenditure. Therapies that target biofilms may provide a significant improvement in the treatment of chronic wounds. Futhermore, the results of this research may impact the treatment of other biofilm-related diseases, such as osteomyelitis, endocarditis, prostatitis, otitis media, and sinusitis.

该项目将解决以下假设：许多慢性伤口愈合不良是由于形成传染性微生物生物膜。已知生物膜优先在死亡或受损的组织上形成，并且有助于持久性，因为生物膜中的微生物逃避抗生素和宿主的杀灭防御。该假设的推论是，有效针对微生物生物膜的疗法将改善这些伤口的愈合。该项目的目标是开发所需的知识和技术评估抗生物膜疗法在伤口愈合中的潜在效用。这将是通过表征伤口生物膜中的存在、形态、结构和氧气可用性来完成（目标#1），开发一套模拟慢性伤口生物膜感染的体外和体内模型伤口生物膜的各个方面（目标#2），并应用这些模型来评估功效和几种潜在抗生物膜技术的安全性（目标#3）。该模型包括多种微生物生物膜在实验室系统中生长，角质形成细胞划痕模型与细菌生物膜（一种筏状器官）相互作用培养模型和慢性伤口感染的小鼠模型。该项目的成功取决于合并来自生物膜科学和技术的专业知识以及伤口愈合方面的专业知识，因此需要由生物膜微生物学家和工程师、皮肤科医生、细胞生物学家和临床医生组成的多学科团队合作者。该项目在三个重要方面具有创新性和高风险性。本项目涉及通过引入伤口愈合领域之外的研究人员来投资生物膜概念。微生物生物膜与组织培养和动物伤口模型的结合是创新的。最后，一些所提出的抗生物膜策略显然是高风险的。无法愈合的伤口，例如糖尿病足溃疡、腿部静脉性溃疡和压疮是发病率、死亡率和医疗保健的主要来源支出。针对生物膜的疗法可能会显着改善慢性病的治疗伤口。此外，这项研究的结果可能会影响其他生物膜相关疾病的治疗，如骨髓炎、心内膜炎、前列腺炎、中耳炎、鼻窦炎等。