Development of Infection-Resistant Suture Materials

抗感染缝合材料的研制

• 批准号: 7226261
• 负责人: Matthew Douglas Phaneuf
• 金额: $ 36.96万
• 依托单位: BIOSURFACES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-15 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7226261
• 关键词: Accounting; Adhesions; Affect; Antibiotic Resistance; Antibiotics; Bacteremia; Bacteria; Bacterial Adhesion; Bacterial Infections; Biocompatible Materials; Biological Assay; Characteristics; Cipro; Ciprofloxacin; Clinical Trials; Condition; Data Analyses; Development; Doxycycline; Dyes; Economics; Edema; Environment; Evaluation; Exposure to; Goals; Growth; Healed; Healthcare Systems; Heating; Hour; In Vitro; Infection; Linezolid; Localized; Marketing; Medical Device; Microbial Biofilms; Modeling; Morbidity - disease rate; Nosocomial Infections; Nylons; Operative Surgical Procedures; Oryctolagus cuniculus; Pain; Pathway interactions; Patients; Penetration; Phase; Phase II Clinical Trials; Play; Polyesters; Polyglactin 910; Postoperative Period; Production; Property; Quality of life; Rate; Research; Research Personnel; Resistance; Resistance to infection; Role; Silk; Site; Solid; Solutions; Surface; Surgical Wound Infection; Surgical sutures; Techniques; Technology; Testing; Textiles; Time; Tissues; Triclosan; United States; United States Food and Drug Administration; Vascular Graft; Vicryl; Week; Wound Healing; Wound Infection; absorption; antimicrobial; antimicrobial drug; base; cost; dacron; day; exhaust; healing; in vivo; mortality; novel; pathogen; physical property; prevent; programs; uptake; wound

DESCRIPTION (provided by applicant): Infection remains as one of the major complications associated with utilizing biomaterials. Surgical site infections account for approximately 14-16% of the 2.4-million nosocomial infections in the United States, with these infections resulting in increased patient morbidity and mortality. The inherent bulk properties of various biomaterials, including those that comprise sutures, provide a milieu for initial bacterial adhesion with subsequent biofilm production and growth. Once the pathogen(s) adheres to the biomaterial surface, treatment with antimicrobial agents is ineffective due to limited penetration of the agent through the bacterial biofilm. Thus, development of a novel infection-resistant suture would provide a localized bacteriocidal environment. In Phase I, Ciprofloxacin (Cipro), Linezolid and Doxycycline were successfully incorporated into nylon, silk and polyester (Dacron) suture materials using textile-dyeing techniques, resulting in infection- resistant suture materials with optimum antimicrobial properties while maintaining the physical properties of the materials. The goal of this Phase II is to evaluate these novel infection-resistant sutures in vivo using a wound infection model. Our hypothesis is that antibiotic-dyed sutures will release antibiotic in a slow, sustained fashion over a period of time as demonstrated in our Phase I in vitro studies, preventing bacterial infection at the suture surface as well as in the surrounding tissue. Current non-degradable suture materials do not possess these characteristics. The specific aims of this study are to: 1) apply antibiotics to nylon, silk and Dacron sutures using dyeing parameters established in Phase I, 2) characterize the physical properties of antibiotic-dyed sutures, 3) determine antibiotic release and antimicrobial activity of antibiotic-dyed sutures using spectrophotometric and in vitro microbiological assays, 4) assess infection-resistance of antibiotic- dyed sutures using a wound infection model and 5) evaluate explanted sutures for localized healing as well as strength using histological and physical testing techniques, respectively. Based on the current infection rates in conjunction with the costs to treat these patients (an average $2,300/episode), surgical wound infection results in an annual cost to the healthcare system of greater than $5 billion. Thus, a significant market exists for application of our technology in order to prevent wound infection.

描述（由申请人提供）：感染仍然是与使用生物材料相关的主要并发症之一。手术部位感染占美国240万医院感染的约14-16%，这些感染导致患者发病率和死亡率增加。各种生物材料（包括包含缝线的生物材料）的固有体积特性为初始细菌粘附以及随后的生物膜产生和生长提供了环境。一旦病原体粘附到生物材料表面，由于抗微生物剂通过细菌生物膜的渗透有限，用抗微生物剂治疗是无效的。因此，新型抗感染缝线的开发将提供局部杀菌环境。在第I阶段，使用纺织品染色技术将环丙沙星（Cipro）、利奈唑胺和多西环素成功掺入尼龙、丝绸和聚酯（涤纶）缝线材料中，从而获得具有最佳抗菌性能的抗感染缝线材料，同时保持材料的物理性能。本II期研究的目的是使用伤口感染模型在体内评价这些新型抗感染缝线。我们的假设是，抗菌染色缝线将在一段时间内以缓慢、持续的方式释放抗生素，正如我们的I期体外研究所证明的那样，防止缝线表面以及周围组织的细菌感染。目前的不可降解缝线材料不具备这些特性。这项研究的具体目标是：1）使用阶段I中确定的染色参数将抗生素应用于尼龙、蚕丝和涤纶缝线，2）表征抗生素染色缝线的物理性能，3）使用分光光度法和体外微生物测定法测定抗生素染色缝线的抗生素释放和抗微生物活性，4）使用伤口感染模型评估抗生素染色缝线的抗感染性，以及5）分别使用组织学和物理测试技术评价染色缝线的局部愈合以及强度。根据目前的感染率以及治疗这些患者的成本（平均2，300美元/次），手术伤口感染导致医疗保健系统每年的成本超过50亿美元。因此，我们的技术在预防伤口感染方面的应用存在着巨大的市场。