Healing Chronic Wounds by Controlling Microbial Biofilm

描述(由申请人提供)：这个项目将解决这一假设，即许多慢性伤口愈合不良是由于形成具有感染性的微生物生物膜。众所周知，生物膜优先在死亡或受损的组织上形成，并有助于持久性，因为生物膜中的微生物逃避抗生素和宿主防御的杀戮。这一假设的一个推论是，有效针对微生物生物膜的治疗将促进这些伤口的愈合。该项目的目标是开发所需的知识和技术，以评估抗生物膜疗法在伤口愈合方面的潜在效用。这将通过表征伤口生物膜的存在、形态、结构和氧气有效性(目标1)，开发一套模拟伤口生物膜不同方面的体外和体内慢性伤口生物膜感染模型(目标2)，并应用这些模型来评估几种潜在的抗生物膜技术的有效性和安全性(目标3)来实现。这些模型包括实验室系统中生长的多菌生物膜、角质形成细胞与细菌生物膜接口的划痕模型、木筏器官培养模型和慢性伤口感染的小鼠模型。这个项目的成功依赖于将生物膜科学和技术的专业知识与伤口愈合方面的专业知识相结合，因此需要一个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组成的多学科团队。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社区以外的调查人员来投资生物膜的概念。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，一些拟议的抗生物被膜策略显然是高风险的。无法愈合的伤口，如糖尿病足部溃疡、静脉性腿部溃疡和压力性溃疡，是发病率、死亡率和卫生保健支出的主要来源。以生物膜为靶点的疗法可能会在慢性伤口的治疗方面提供显着改善。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、中耳炎和鼻窦炎。

DESCRIPTION (provided by applicant): 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 persistence because microorganisms in biofilms evade killing 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. He 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. Furthermore, the results of this research may impact the treatment of other biofilm-related diseases, such as osteomyelitis, endocarditis, prostatitis, otitis media, and sinusitis.