Photoactivated Antimicrobial Collagen

光活化抗菌胶原蛋白

• 批准号: 7668289
• 负责人: BARBARA Ann SOLTZ
• 金额: $ 10.01万
• 依托单位: CONVERSION ENERGY ENTERPRISES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7668289
• 关键词: Acute; Ambulatory Care Facilities; Animals; Antibiotics; Bacteria; Bacterial Antibiotic Resistance; Bacteriophages; Biochemistry; Biocompatible; Biocompatible Materials; Caring; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chronic; Cicatrix; Collagen; Communities; Complex; Cutaneous; DNA; Data; Decubitus ulcer; Development; Devices; Doctor of Philosophy; Dose; Drug Carriers; Electronics; Emergency treatment; Film; Flavins; General Hospitals; Generations; Genes; Genetic Materials; Goals; Growth; Habitats; Healed; Health care facility; Histology; Hospitalization; Hospitals; Human; In Vitro; Incidence; Infection; Injury; Inpatients; Laser Surgery; Lasers; Lead; Legal patent; Length of Stay; Light; Medical; Methods; Microbial Biofilms; Military Personnel; Modeling; Modification; Morbidity - disease rate; Mutation; Nosocomial Infections; Nucleotides; Operative Surgical Procedures; Outcome; Oxidation-Reduction; Patient Care; Patients; Performance; Phase; Phenotype; Plasmids; Polymers; Population; Predisposition; Preparation; Prevalence; Principal Investigator; Property; RNA; Reporting; Research; Resistance; Resistance development; Resources; Risk; Solutions; Source; Sterile coverings; Structure; Surface; Surgical Wound Infection; Surgical wound; Technology; Testing; Time; Topical application; Toxic effect; Treatment Efficacy; Virus; Visceral; Visible Radiation; Work; Wound Healing; Wound Infection; absorption; antimicrobial; antimicrobial drug; bactericide; base; chromophore; controlled release; conventional therapy; cost; culture plates; design; disability; experience; free radical oxygen; healing; improved; in vitro activity; in vitro testing; in vivo; innovation; methicillin resistant Staphylococcus aureus; microbial; microorganism; mortality; novel; novel strategies; pathogen; pressure; prevent; public health relevance; skills; stem; tool; trend; user-friendly; wound

DESCRIPTION (provided by applicant): The significance of this project is the development of a novel photoactivated collagen dressing with demonstrated bactericidal effects, minimal toxic effects and low susceptibility to mechanisms of microbial resistance in an effort to ultimately expand the armamentarium of antimicrobial agents for the management of wound infections. Approximately 2 million patients develop hospital-acquired (nosocomial) infections with surgical wound infections being the most common. It has been reported that 1 of every 24 (4.1%) patients who have inpatient surgery in the US develops a wound infection. These infections are substantial in terms of their impact on morbidity, mortality and resource use. As many as 100,000 deaths and staggering costs of $3.5B annually are associated with wound infections. In the US wound infections increase costs of hospitalization by more than $3,000/patient. While the conventional treatment of infections includes both focused and broad-spectrum antibiotics there has been a continuing and alarming trend of microbial resistance to these agents. This resistance is believed to occur as a result of chromosomal mutation, inductive expression of a latent chromosomal genes or exchange of genetic material via transformation, bacteriophage transduction, or plasmid conjugation. A preliminary study demonstrated in vitro activity of a light activated, flavin solution against methicillin-resistant Staphylococcus aureus (MRSA). These results suggest that a method could be developed to prevent wound infections and accelerate wound healing using this approach. It is believed that the antimicrobial properties of light-exposed flavin solutions stem from release of oxygen free radicals in combination with the generation of nucleotides that preferentially interrupt the RNA or DNA of pathogens. Development of resistance is unlikely, given the mechanism of action of these compounds. Such a strategy could potentially be effective against a broad spectrum of pathogens including bacteria and viruses. It is proposed to establish feasibility of photoactivated collagen dressings in both in vitro and in vivo studies. The Phase I application describes work to optimize the performance of the collagen dressing. Project tasks include the preparation of collagen dressing, the modification of light sources for optimizing activation parameters and chronic wound models with endpoints including histology and wound cultures. PUBLIC HEALTH RELEVANCE: Millions of surgical and iatrogenic wounds occur on an annual basis. Each requires appropriate management to facilitate healing, reduce the potential for infection and minimize disability and scarring. Wound infection and related complications increase the cost of care by nearly $9000 per occurrence and prolong hospital stays. At the same time, bacterial resistance to antibiotics is increasing at an alarming rate, with community acquired MRSA (Methicillin-resistant Staphylococcus aureus) prevalence approaching 50% in several communities based on wound culture data. This project aims to develop a novel strategy using a combination of visible light and redox-active chromophores to expand the armamentarium of antimicrobial agents for the management of surgical wounds.

描述（由申请人提供）：该项目的意义在于开发一种新型光活化胶原敷料，该敷料具有杀菌作用，毒性作用最小，对微生物耐药机制的易感性低，最终努力扩大抗菌药物的装备，用于伤口感染的管理。大约有200万患者发生医院获得性感染，其中最常见的是手术伤口感染。据报道，在美国，每24例住院手术患者中就有1例（4.1%）发生伤口感染。这些感染对发病率、死亡率和资源使用的影响是巨大的。每年与伤口感染有关的死亡人数多达10万人，费用高达35亿美元。在美国，伤口感染使每位患者的住院费用增加了3000多美元。虽然感染的常规治疗包括集中抗生素和广谱抗生素，但微生物对这些药物的耐药性已经出现了持续和令人担忧的趋势。这种抗性被认为是由于染色体突变、潜在染色体基因的诱导表达或通过转化、噬菌体转导或质粒偶联交换遗传物质而发生的。初步研究表明，光活化黄素溶液对耐甲氧西林金黄色葡萄球菌（MRSA）的体外活性。这些结果表明，可以开发一种方法来预防伤口感染，并利用这种方法加速伤口愈合。人们认为，暴露在光下的黄素溶液的抗菌特性源于氧自由基的释放，以及核苷酸的产生，这些核苷酸优先中断病原体的RNA或DNA。鉴于这些化合物的作用机制，不太可能产生耐药性。这种策略可能对包括细菌和病毒在内的多种病原体有效。建议在体外和体内研究中建立光活化胶原敷料的可行性。第一阶段的申请描述了优化胶原蛋白敷料性能的工作。项目任务包括制备胶原蛋白敷料，修改光源以优化激活参数和慢性伤口模型，终点包括组织学和伤口培养。公共卫生相关性：每年发生数百万例外科和医源性伤口。每一种都需要适当的治疗，以促进愈合，减少感染的可能性，并尽量减少残疾和疤痕。伤口感染和相关并发症使每次发生的护理费用增加近9000美元，并延长住院时间。与此同时，细菌对抗生素的耐药性正以惊人的速度增加，根据伤口培养数据，在一些社区，社区获得性MRSA（耐甲氧西林金黄色葡萄球菌）的患病率接近50%。该项目旨在开发一种利用可见光和氧化还原活性发色团相结合的新策略，以扩大抗菌药物的装备，用于外科伤口的管理。