Photoactivated Antimicrobial Collagen

光活化抗菌胶原蛋白

• 批准号: 8312845
• 负责人: BARBARA Ann SOLTZ
• 金额: $ 32.67万
• 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 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8312845
• 关键词: Abscess; Acute; Ambulatory Care Facilities; Animals; Antibiotics; Area; Bacteria; Bacterial Antibiotic Resistance; Bacteriophages; Beds; Biochemistry; Biocompatible; Biocompatible Materials; Caring; Cessation of life; Chronic; Cicatrix; Clinical Research; Collagen; Collagen Type I; Colony-forming units; Communities; DNA; Data; Decubitus ulcer; Development; Devices; Doctor of Philosophy; Documentation; Dose; Drug Carriers; Effectiveness; Electronics; Emergency Situation; Ensure; Environment; Escherichia coli Infections; Family suidae; Film; Flavins; General Hospitals; Generations; Genes; Genetic Materials; Growth; Guidelines; Healed; Hematoma; Histopathology; Hospitalization; Hospitals; Human; In Vitro; Incidence; Infection; Inpatients; Laser Surgery; Lasers; Lead; Legal patent; Length of Stay; Light; Measures; Medical; Methods; Microbial Biofilms; Modeling; Morbidity - disease rate; Mutation; Nosocomial Infections; Nucleotides; Operating Rooms; Operative Surgical Procedures; Optics; Output; Oxidation-Reduction; Patients; Performance; Phase; Physiologic pulse; Plasmids; Predisposition; Preparation; Prevalence; Principal Investigator; Procedures; Process; Property; Pseudomonas aeruginosa; RNA; Reaction; Reagent; Reporting; Research; Resistance; Resistance development; Resources; Riboflavin; Sampling; Seroma; Source; Staphylococcus aureus; Sterile coverings; Surgical Wound Infection; Surgical incisions; Surgical wound; System; Technology; Testing; Time; Tissues; Toxic effect; Visible Radiation; Work; Wound Healing; Wound Infection; antimicrobial; antimicrobial drug; bacterial resistance; bactericide; base; chromophore; controlled release; conventional therapy; cost; design; disability; experience; free radical oxygen; healing; in vivo; methicillin resistant Staphylococcus aureus; microbial; mortality; mouse model; novel; novel strategies; open wound; pathogen; phase 1 study; pre-clinical; prevent; research study; skills; technological innovation; treatment strategy; trend; 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. In-vitro and in-vivo experiments were successfully performed during Phase I. It was demonstrated that the light activated dressings significantly inhibits bacterial growth in-vitro, including biofilm scenarios. In addition, the effect is robust, reducing bacterial loads in-vivo in infected incision, wound abscess and pressure ulcer models. Similar results were obtained for Staphylococcus aureus, MRSA, Pseudomonas aeruginosa and Escherichia coli infections. The current proposal specifically aims to further refine the use of photoactivated antimicrobial collagen technology as a wound treatment to augment wound closure and healing, thereby reducing the incidence of acute and chronic wound infections. The studies performed will provide important preclinical results designed to optimize materials for human clinical studies and FDA approval. 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，该敷料具有已证明的杀菌作用、最小的毒性作用和对微生物耐药机制的低敏感性，以最终扩大用于治疗伤口感染的抗菌药物的武器库。大约 200 万患者出现医院获得性（院内）感染，其中手术伤口感染最为常见。据报道，在美国每 24 名接受住院手术的患者中就有 1 名（4.1%）出现伤口感染。这些感染对发病率、死亡率和资源利用的影响是巨大的。每年有多达 100,000 人死亡，费用高达 $3.5B，与伤口感染有关。在美国，伤口感染会使每位患者的住院费用增加超过 3,000 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一直呈持续且令人震惊的趋势。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、噬菌体转导或质粒接合而交换遗传物质而发生的。第一阶段成功进行了体外和体内实验。结果表明，光激活敷料可显着抑制体外细菌生长，包括生物膜情况。另外，效果也很强劲， 减少感染切口、伤口脓肿和压疮模型中的体内细菌负荷。金黄色葡萄球菌、MRSA、铜绿假单胞菌和大肠杆菌感染也获得了类似的结果。目前的提案特别旨在进一步完善光活化抗菌胶原技术作为伤口治疗的使用，以促进伤口闭合和愈合，从而减少急性和慢性伤口感染的发生率。所进行的研究将提供重要的临床前结果，旨在优化人类临床研究和 FDA 批准的材料。 公共卫生相关性：每年都会发生数以百万计的手术和医源性伤口。每个都需要适当的管理以促进愈合、减少感染的可能性并尽量减少残疾和疤痕。每次发生伤口感染和相关并发症都会使护理费用增加近 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，一些社区的 MRSA（耐甲氧西林金黄色葡萄球菌）患病率接近 50%。该项目旨在开发一种结合可见光和氧化还原活性发色团的新策略，以扩大用于治疗手术伤口的抗菌药物的武器库。