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）：该项目的重要性是开发一种新型的光活化胶原蛋白敷料，具有杀菌作用，最小的毒性作用和对微生物耐药机制的敏感性低，以最终扩大抗微生物剂的抗微生物抗体，以促进伤口感染的管理。大约有200万患者会出现医院的（医院医院）感染，而手术伤口感染最为常见。据报道，在美国接受住院手术的每24名（4.1％）患者中，有1例会出现伤口感染。这些感染在对发病率，死亡率和资源使用的影响方面很重要。每年多达100,000人死亡和$ 3.5B的惊人费用与伤口感染有关。在美国，伤口感染使住院费用增加了3,000多美元。虽然传统的感染治疗包括聚焦和广谱抗生素，但微生物对这些药物的耐药性持续而令人震惊。据信这种耐药性是由于染色体突变，潜在染色体基因的感应表达或通过转化，噬菌体转导或质粒结合而产生的。一项初步研究表明，针对金黄色葡萄球菌（MRSA）激活的黄素溶液在体外活性。这些结果表明，可以开发一种方法来防止伤口感染并使用这种方法加速伤口愈合。据认为，光暴露黄素溶液的抗菌特性源于氧气自由基的释放以及优先中断病原体RNA或DNA的核苷酸的产生。鉴于这些化合物的作用机理，抗性的发展不可能。这种策略可能有效地针对包括细菌和病毒在内的各种病原体。建议在体外和体内研究中建立光活化胶原蛋白敷料的可行性。 I阶段应用程序描述了优化胶原蛋白敷料性能的工作。项目任务包括胶原蛋白敷料的制备，用于优化激活参数的光源的修饰以及具有终点（包括组织学和伤口培养物）的慢性伤口模型。公共卫生相关性：每年发生数百万手术和医源性伤口。每个人都需要适当的管理来促进康复，减少感染的可能性，并最大程度地减少残疾和疤痕。伤口感染和相关并发症增加了每次发生的护理费用近9000美元，并延长了住院时间。同时，对抗生素的细菌耐药性正在以惊人的速度增加，社区获得了基于伤口培养数据的几个社区的MRSA（耐甲氧西林的金黄色葡萄球菌）的患病率接近50％。该项目旨在使用可见光的光和氧化还原活性发色团结合制定一种新的策略，以扩大抗菌剂的武器群来治疗手术伤口。