Initiation of blood coagulation - Evaluating the relevance of specific surface functionalities using self assembled monolayers

本项目旨在测试最近阐明的体内凝血途径对生物材料表面凝血和血细胞激活的影响。为了更合理地设计与血液相容的表面，需要对材料-血液相互作用有更深入的了解。最近对凝血过程的认识，特别是细胞系统的参与，还没有被整合到血液相容性研究中，主要焦点仍然放在接触系统的激活上。研究中将使用具有不同表面官能度(-COOH、-OH、-CH3)的自组装单分子膜的模型表面，以及具有不同组成的双组分层，因为它们允许修改单个参数。以前的实验结果表明，血小板黏附增强，尤其是在-CH3-表面，白细胞在羟基终止的表面，并且-CH3-和COOH-基团对血浆凝血激活有协同作用。这表明细胞系统对血浆凝血的影响，这不在一般的表面血液相容性概念中。该系统将用于系统地检查不同表面化学对凝血激活的影响、组织因子(外源性/激活剂途径)、接触激活(内在/增强子途径)和细胞系统(血小板和白细胞)的影响。

This project intends to test the impact of recently elucidated pathways of coagulation in vivo on coagulation and blood cell activation at biomaterial surfaces. Targeting for a more rational design of blood compatible surfaces requires a deeper understanding of material ¿ blood interactions. Recent insights in coagulation processes, especially the involvement of cellular systems, have not yet been integrated in hemocompatibility research yet where the main focus is still set on the activation of the ¿contact system¿. Model surfaces of self assembled monolayers with different surface functionalities (-COOH, -OH, -CH3) as well as two-component-layers with varying fractions of these will be used in the study, as they allow the modification of single parameters. Previous results with this system indicated an enhanced platelet adhesion preferably on -CH3-surfaces, leukocytes on OH-terminated surfaces and a synergistic effect of -CH3- and COOH-groups on plasmatic coagulation activation. This indicates an influence of the cellular systems on the plasmatic coagulation what is not in the general concept of blood compatibility of surfaces. The system will be used to check systematically the effects of different surface chemistry on the coagulation activation, impact of tissue factor (extrinsic/ activator pathway), contact activation (intrinsic/ enhancer pathway) and cellular systems (blood platelets and leukocytes).