Development of Infection-Resistant Suture Materials

描述(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。在美国240万医院感染中，手术部位感染约占14-16%，这些感染导致患者发病率和死亡率增加。各种生物材料固有的体积特性，包括那些包含缝合线的材料，为最初的细菌与随后的生物膜生产和生长提供了一个环境。一旦病原体(S)附着在生物材料表面，抗菌剂的治疗就会无效，因为抗菌剂对细菌生物膜的渗透有限。因此，开发一种新型的抗感染缝线将提供一个局部的杀菌环境。在第一阶段中，利用织物染色技术，将环丙沙星、利奈唑胺和强力霉素成功地加入到尼龙、丝绸和涤纶(Dacron)缝合材料中，在保持材料物理性能的同时，获得了具有最佳抗菌性能的抗感染缝合材料。这一阶段的目标是使用伤口感染模型在体内评估这些新型抗感染缝合线。我们的假设是，抗生素染色的缝合线将在一段时间内缓慢、持续地释放抗生素，正如我们的第一阶段体外研究所证明的那样，防止缝合面以及周围组织的细菌感染。目前的不可降解缝合材料不具备这些特性。本研究的具体目的是：1)使用第一阶段建立的染色参数将抗生素应用于尼龙、丝绸和涤纶缝合线；2)表征抗生素染色缝合线的物理性质；3)使用分光光度法和体外微生物检测方法测定抗生素染色缝合线的抗生素释放和抗菌活性；4)使用伤口感染模型评估抗生素染色缝合线的抗感染性；5)分别使用组织学和物理测试技术评估移植缝合线的局部愈合和强度。根据目前的感染率和治疗这些患者的费用(平均每例2300美元)，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，应用我们的技术来预防伤口感染是一个巨大的市场。

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.