Healing Chronic Wounds by Controlling Microbial Biofilm

这个项目将解决的假设，许多慢性伤口愈合不良是由于形成 感染性微生物生物膜已知生物膜优先在死亡或受损组织上形成， 有助于持久存在，因为生物膜中的微生物逃避抗生素和宿主的侵袭 的防御合作.该假说的一个推论是，有效靶向微生物生物膜的疗法将改善 治愈这些伤口。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背景下的潜在效用。这将是 通过表征伤口生物膜中的存在、物种形成、结构和氧气利用率来实现 (Aim#1），开发了一套模拟慢性伤口生物膜感染的体外和体内模型， 伤口中生物膜的不同方面（目标#2），并应用这些模型来评估疗效和 几种潜在的抗生物膜技术的安全性（目标#3）。模型包括多微生物生物膜 在实验室系统中生长的角质形成细胞划痕模型与细菌生物膜连接， 培养模型和慢性伤口感染的小鼠模型。这个项目的成功取决于合并 具有伤口愈合专业知识的生物膜科学和技术的专业知识，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 合作者该项目在三个重要方面具有创新性和高风险性。这个项目涉及 通过引入伤口愈合界以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，如糖尿病足 溃疡、静脉性腿部溃疡和压力性溃疡是发病率、死亡率和卫生保健的主要来源 支出靶向生物膜的疗法可以在慢性肿瘤的治疗中提供显著的改善。 伤口然而，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、中耳炎和鼻窦炎。

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.