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: 7682238
• 负责人: PHILIP S STEWART
• 金额: $ 65.79万
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7682238
• 关键词: Address; Animals; Antibiotics; Cells; Chronic; Clinical; Communities; Decubitus ulcer; Dermatologist; Diabetic Foot Ulcer; Disease; Endocarditis; Engineering; Goals; Healed; Health Expenditures; Host Defense; In Vitro; Infection; Knowledge; Laboratories; Leg Ulcer; Marriage; Microbial Biofilms; Modeling; Morbidity - disease rate; Organ Culture Techniques; Osteomyelitis; Otitis Media; Oxygen; Research; Research Personnel; Safety; Science; Simulate; Sinusitis; Source; Structure; System; Techniques; Technology; Tissues; Venous; Wound Healing; Wound Infection; healing; high risk; improved; in vivo Model; innovation; keratinocyte; killings; microorganism; mortality; mouse model; multidisciplinary; prostatitis; success; tissue culture; wound

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.

描述（由申请人提供）：该项目将解决许多慢性伤口愈合不良是由于感染性微生物生物膜形成的假设。 已知生物膜优先在死亡或受损组织上形成，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防御的杀死。 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。 该项目的目标是开发评估抗生物膜疗法在伤口愈合背景下的潜在效用所需的知识和技术。 这将通过表征伤口生物膜中的存在、物种形成、结构和氧可用性（目标#1），开发一套模拟伤口中生物膜的不同方面的慢性伤口生物膜感染的体外和体内模型（目标#2），并应用这些模型来评价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。 这些模型包括在实验室系统中生长的多微生物生物膜、与细菌生物膜连接的角质形成细胞划痕模型、筏状器官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将生物膜科学和技术的专业知识与伤口愈合的专业知识相结合，因此需要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。 该项目涉及通过引入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是创新的。 最后，一些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、死亡率和医疗保健支出的主要来源。 靶向生物膜的疗法可以在慢性伤口的治疗中提供显著的改善。 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。

项目成果

In vitro susceptibility of established biofilms composed of a clinical wound isolate of Pseudomonas aeruginosa treated with lactoferrin and xylitol.

• DOI: 10.1016/j.ijantimicag.2008.08.013
• 发表时间: 2009-03
• 期刊: International journal of antimicrobial agents
• 影响因子: 10.8
• 作者: Ammons MC;Ward LS;Fisher ST;Wolcott RD;James GA
• 通讯作者: James GA

Time course study of delayed wound healing in a biofilm-challenged diabetic mouse model.

在生物膜挑战的糖尿病小鼠模型中伤口愈合延迟伤口愈合的时间过程。

• DOI: 10.1111/j.1524-475x.2012.00793.x
• 发表时间: 2012-05
• 期刊: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
• 作者: Zhao G;Usui ML;Underwood RA;Singh PK;James GA;Stewart PS;Fleckman P;Olerud JE
• 通讯作者: Olerud JE

Delayed wound healing in diabetic (db/db) mice with Pseudomonas aeruginosa biofilm challenge: a model for the study of chronic wounds.

• DOI: 10.1111/j.1524-475x.2010.00608.x
• 发表时间: 2010-09
• 期刊: Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
• 作者: Zhao G;Hochwalt PC;Usui ML;Underwood RA;Singh PK;James GA;Stewart PS;Fleckman P;Olerud JE
• 通讯作者: Olerud JE

Resident bacterial flora in the skin of C57BL/6 mice housed under SPF conditions.

SPF 条件下饲养的 C57BL/6 小鼠皮肤中的常驻细菌菌群。

• 发表时间: 2010
• 期刊: Journal of the American Association for Laboratory Animal Science : JAALAS
• 作者: Tavakkol,Zarry;Samuelson,Derrick;deLanceyPulcini,Elinor;Underwood,RobertA;Usui,MarciaL;Costerton,JWilliam;James,GarthA;Olerud,JohnE;Fleckman,Philip
• 通讯作者: Fleckman,Philip

Development and application of a polymicrobial, in vitro, wound biofilm model.

• DOI: 10.1111/j.1365-2672.2012.05264.x
• 发表时间: 2012-05
• 期刊: Journal of applied microbiology
• 影响因子: 4
• 作者: Woods J;Boegli L;Kirker KR;Agostinho AM;Durch AM;Delancey Pulcini E;Stewart PS;James GA
• 通讯作者: James GA