Development of Infection-Resistant Suture Materials

描述（由申请人提供）：感染仍然是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。各种生物材料的固有体积特性，包括那些包含缝合线的材料，为初始细菌粘附和随后的生物膜生产和生长提供了环境。一旦病原体附着在生物材料表面，抗菌剂的治疗就无效了，因为抗菌剂通过细菌生物膜的渗透能力有限。因此，新型抗感染缝合线的开发将提供局部杀菌环境。在一期研究中，采用纺织染色技术将环丙沙星（Cipro）、利奈唑胺（Linezolid）和强力霉素（Doxycycline）成功掺入尼龙、丝绸和涤纶（涤纶）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。本二期研究的目的是利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以缓慢、持续的方式释放抗生素，正如我们在I期体外研究中所证明的那样，防止缝合线表面和周围组织的细菌感染。目前不可降解的缝合材料不具备这些特性。本研究的具体目的是：1)使用I期建立的染色参数将抗生素应用于尼龙、丝绸和涤纶缝线，2)表征抗生素染色缝线的物理特性，3)使用分光光度法和体外微生物测定抗生素染色缝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线的感染耐药性，5)分别使用组织学和物理测试技术评估外植缝线的局部愈合和强度。根据目前的感染率以及治疗这些患者的费用（平均2300美元/次），外科伤口感染导致医疗保健系统每年的费用超过50亿美元。因此，我们的技术在预防伤口感染方面的应用有很大的市场。

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.