Endothelial Adhesion Molecules and Leukocyte Egress

描述(由申请人提供)： 大约80%的患者在住院时需要静脉导管。导管相关感染约占所有并发症的一半，而导管诱导的血栓形成(纤维蛋白鞘形成和壁血栓形成)占所有与导管长期存在于血管系统相关的故障的25%。近年来，为了改善材料的生物相容性，人们对血液相容性涂层进行了研究，目的是通过减少蛋白质的粘附性来降低血栓形成能力。大量研究表明，通过表面修饰可以显著降低异物表面的血栓形成特性。表面生物化技术中最有前景的一种是表面活性聚合物涂层(SPC)，它试图模拟自然环境，特别是血管内皮细胞的糖基化特性。体外研究表明，SPC可显著降低纤维蛋白原、血小板黏附和活化。SPC的另一个实用优势是其低成本和在医疗器械表面应用的简单性。在第一阶段，我们通过与中心静脉导管所经历的剪切速率相对应的体外剪切研究来确定聚氨酯表面活性物质涂层的稳定性。此外，通过使用狗模型进行的一系列体外实验，我们确定SPC减少了纤维蛋白原和血小板对涂层表面的黏附。减少了80%以上的血小板与SPC的黏附。在未涂覆的医用级聚氨酯表面上进行了演示。这证明了SPCS作为中心静脉导管的可行性。第二阶段研究的目的是通过在大鼠体内长期使用的研究来验证涂层的生物相容性。我们的研究将集中在两个方面：SPC减少导管表面的纤维套筒和SPC减少导管相关感染。在第二阶段成功完成后，我们将准备开始人体临床试验，并完成商业化进程。

DESCRIPTION (provided by applicant): Approximately 80% of patients require an intravenous catheter upon hospitalization. Catheter-related infection comprises approximately half of all complications while catheter-induced thrombosis (fibrin sheath formation and mural thrombosis) compound 25% of all failures associated with catheter long-term presence in the vascular system. Blood compatible coatings have been investigated in recent years in order to improve material biocompatibility by reducing thrombogenicity through diminished protein adhesion. Numerous studies indicate that thrombogenic properties of a foreign surface can be significantly reduced by surface modifications. One of the more promising types of surface biolization technologies is a surfactant polymer coating (SPC) that attempts to mimic nature, in particular the properties of glycocalyx of vascular endothelium cells. It has been demonstrated through in vitro studies that SPC significantly reduces fibrinogen, and platelet adhesion and activation. Additional practical advantages of SPC are its low cost and simplicity of application to the surface of medical device. In Phase I, we determined the stability of the surfactant coating on polyurethane through in vitro shear studies corresponding to the shear rates experienced by a central venous catheter. Further, through series of ex vivo experiments using dog models, we determined that the SPC reduces fibrinogen and platelet adhesion to the coated surfaces. A reduction of over 80% of platelet adhesion to the SPC. was demonstrated in reference to non-coated medical grade polyurethane surfaces. This demonstrated the feasibility of SPCs for central venous catheters. The aim of Phase II research is to validate the biocompatibility of the coatings through in vivo studies in rats for long-term use. We will focus our investigation on two aspects: reduction of the fibrous sleeve on the catheter surface by SPC and reduction of catheter-related infections with SPC. After successful Phase II completion, we will be prepared to start human clinical trials and to finish the commercialization process.