Sarkar Sandip, Sales Kevin M, Hamilton George, Seifalian Alexander M
Biomaterials and Tissue Engineering Centre (BTEC), Academic Division of Surgical and Interventional Sciences, University College London, London, United Kingdom.
J Biomed Mater Res B Appl Biomater. 2007 Jul;82(1):100-8. doi: 10.1002/jbm.b.30710.
Thrombosis is a major cause of poor patency in synthetic vascular grafts for small diameter vessel (< 6 mm) bypass. Arteries have a host of structural mechanisms by which they prevent triggering of platelet activation and the clotting cascade. Many of these are present in vascular endothelial cells. These mechanisms act together with perpetual feedback at different levels, providing a constantly fine-tuned non-thrombogenic environment. The arterial wall anatomy also serves to promote thrombosis as a healing mechanism when it has been severely injured. Surface modification of synthetic graft surfaces to attenuate the coagulation cascade has reduced thrombosis levels and improved patency in vitro and in animal models. Success in this endeavor is critically dependent on the methods used to modify the surface. Platelets adhere to positively charged surfaces due to their own negative charge. They also preferentially attach to hydrophobic surfaces. Therefore synthetic graft development is concerned with hydrophilic materials with negative surface charge. However, fibrinogen has both hydrophilic and hydrophobic binding sites-amphiphilic materials reduce its adhesion and subsequent platelet activation. The self-endothelializing synthetic graft is an attractive proposition as a confluent endothelial layer incorporates many of the anti-thrombogenic properties of arteries. Surface modification to promote this has shown good results in animal models. The difficulties experienced in achieving spontaneous endothelialisation in humans have lead to the investigation of pre-implantation in vitro endothelial cell seeding. These approaches ultimately aim to result in novel synthetic grafts which are anti-thrombogenic and hence suitable for coronary and distal infrainguinal bypass.
血栓形成是小直径血管（<6mm）旁路合成血管移植物通畅性差的主要原因。动脉具有一系列结构机制，可防止血小板活化和凝血级联反应的触发。其中许多机制存在于血管内皮细胞中。这些机制在不同水平上与持续的反馈共同作用，提供一个不断微调的非血栓形成环境。当动脉壁受到严重损伤时，其解剖结构也有助于促进血栓形成作为一种愈合机制。对合成移植物表面进行表面改性以减弱凝血级联反应，已在体外和动物模型中降低了血栓形成水平并改善了通畅性。这项工作的成功关键取决于用于改性表面的方法。由于血小板自身带负电荷，它们会粘附在带正电荷的表面。它们还优先附着在疏水表面上。因此，合成移植物的开发涉及具有负表面电荷的亲水材料。然而，纤维蛋白原具有亲水和疏水结合位点——两亲性材料可减少其粘附和随后的血小板活化。自内皮化合成移植物是一个有吸引力的提议，因为汇合的内皮细胞层具有动脉的许多抗血栓形成特性。促进这一过程的表面改性在动物模型中已显示出良好的效果。在人类中实现自发内皮化所遇到的困难导致了对植入前体外内皮细胞接种的研究。这些方法最终旨在产生新型的抗血栓形成合成移植物，因此适用于冠状动脉和远端股下旁路手术。
