Healing Chronic Wounds by Controlling Microbial Biofilm

通过控制微生物生物膜治愈慢性伤口

• 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
• 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

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：许多慢性伤口的治愈不佳是由于形成 传染性微生物生物膜。已知生物膜在死亡组织或受损的组织中优先形成 由于生物膜中的微生物逃避抗生素和宿主的杀伤而导致蠕动 防御。该假设的推论是，有效靶向微生物生物膜的疗法将改善 这些伤口的愈合。该项目的目的是发展所需的知识和技术 在伤口愈合的背景下评估抗生物胶质膜疗法的潜在效用。这将是 通过表征伤口生物膜中的存在，物种形成，结构，干燥氧的可用性来完成 （AIM＃1），开发一套体外和体内模型的慢性伤口生物膜感染模型 伤口中生物膜的各个方面（AIM＃2），并应用这些模型来评估功效和 几种潜在的抗生物膜技术的安全性（AIM＃3）。这些模型包括多生物生物膜 在实验室系统中生长，一种与细菌生物膜连接的角质形成细胞划痕模型 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 生物膜科学技术的专业知识在伤口愈合方面具有专业知识，因此需要一个 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。这个项目涉及 通过吸引在伤口愈合社区之外的调查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具有创新性。最后，有些 拟议的抗生物膜策略显然是高风险的。无法愈合的伤口，例如糖尿病脚 溃疡，静脉溃疡和压疮是发病率，死亡率和医疗保健的主要来源 支出。靶向生物膜的疗法可以在慢性治疗方面有显着改善 伤口。 futhermore，这项研究的结果可能会影响其他生物膜相关疾病的治疗 例如骨髓炎，心内膜炎，前列腺炎，中耳炎和鼻窦炎。