Research and development of the small caliber artificial blood vessel with antithrombogenicity

嵌段共聚物表面具有交替层状的微相分离结构，通过抑制血小板黏附和活化而显示出良好的抗血栓形成性能。采用自行研制的微球柱法，体外检测了血小板与样品材料的粘附性。在PHEMA或聚苯乙烯等均聚物表面，大量的血小板黏附、聚集并广泛激活，形成血栓。反之，嵌段共聚物如HEMA-St、FAA-St对血小板黏附有明显的抑制作用。结果表明，由HEMA和ST或FAA和ST组成的微区之间的表面自由能隙是形成有序稳定的吸附蛋白质层的决定性因素，对血小板的黏附和活化有强烈的影响。此外，延长的血小板聚集时间(PAT)清楚地表明，在微相分离结构的表面上，黏附的血小板的激活被有效地抑制。在体外实验(兔动静脉分流)中，嵌段型共聚物的移植物开放时间明显长于均聚物的移植物。在均聚体移植的情况下，循环血小板的数量和功能的时程变化显著。另一方面，在嵌段共聚物的情况下，分流形成后循环血小板的数量和功能维持在正常范围。结果表明，嵌段共聚物具有良好的抗凝血性能和血液相容性。在犬冠状动脉旁路实验中，内径1.5 mm的HEMA-ST涂层人工血管保持通畅达4周。

The surface of block type copolymers having microphase separated structure of alternating lamellar type shows the excellent antithrombogenicity through the suppression of platelet adhesion and platelet activation. By using the microsphere-column method which was developed by us, adhesion of platelets on sample materials was examined in vitro. On the surface of homopolymer such as PHEMA or polystyrene, a large amount of platelets adhered, aggregated and extensively activated to form thrombus. On the contrary, platelet adhesion was significantly suppressed on the block type copolymer such as HEMA-St, FAA-St. It was indicated that the surface free energy gap between microdomains consisted of HEMA and St, or FAA and St was the determinant factor in formation of organized and stable layer of adsorbed proteins which gave intense influence to platelet adhesion and activation. In addition, prolonged platelet aggregation time (PAT) clearly indicates that the activation of adhered platelets was effectively inhibited on the surfaces with microphase separated structure.In ex vivo experiment (rabbit A-V shunt), duration of graft patency made of block type copolymers was distinguishably longer than of graft made of homopolymer. Time-course change in number and function of circulating platelets was remarkable in case of graft made of homopolymer. On the other hand, in case of block copolymer, the number and function of circulating platelets were maintained in the normal range after shunt formation. From these results, the excellent antithrombogenicity and hemocompatibility of the block type copolymers was confirmed. In coronary by-pass experiment in dogs, 1.5 mm internal diameter prosthetic tube coated with HEMA-St was kept it patency as long as four weeks.