Endothelial Adhesion Molecules and Leukocyte Egress

内皮粘附分子和白细胞排出

• 批准号: 7058852
• 负责人: JAN JERZY LEWANDOWSKI
• 金额: $ 73.43万
• 依托单位: ELECTROSONICS MEDICAL INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7058852
• 关键词: biomaterial compatibility; biomaterial development /preparation; biomaterial evaluation; biomimetics; biotechnology; catheterization; clinical research; human subject; laboratory rat; polymers; surface coating; surfactant

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.

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（纤维蛋白鞘形成和附壁血栓形成）占与导管长期存在于血管系统相关的所有失效的25%。近年来研究了血液相容性涂层，以通过减少蛋白质粘附来减少血栓形成，从而改善材料的生物相容性。 大量研究表明，表面改性可显著降低异物表面的血栓形成特性。表面生物化技术的更有前途的类型之一是表面活性剂聚合物涂层（SPC），其试图模拟自然，特别是血管内皮细胞的糖萼的性质。体外研究表明，SPC可显著降低纤维蛋白原、血小板粘附和活化。SPC的其他实际优点是其低成本和简单的应用到医疗设备的表面。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上表面活性剂涂层的稳定性。此外，通过使用狗模型的一系列离体实验，我们确定SPC减少纤维蛋白原和血小板粘附到涂覆的表面。血小板对SPC的粘附减少80%以上。在未涂覆的医用级聚氨酯表面上进行了证明。这证明了SPC用于中心静脉导管的可行性。II期研究的目的是通过在大鼠体内进行长期使用的研究来验证涂层的生物相容性。我们将集中研究两个方面：SPC减少导管表面的纤维套管和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过程。