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

具有交替层状微相分离结构的嵌段共聚物表面通过抑制血小板粘附和血小板活化而显示出优异的抗血栓性。采用自行研制的微球-柱法，在体外观察血小板在材料表面的粘附情况。在均聚物如PHEMA或聚苯乙烯表面，大量血小板粘附、聚集并广泛活化形成血栓。而在嵌段共聚物HEMA-St、FAA-St上，血小板粘附则受到明显抑制，表明HEMA与St或FAA与St组成的微区之间的表面自由能隙是形成有序、稳定的蛋白吸附层的决定性因素，对血小板的粘附和活化有重要影响。此外，血小板聚集时间（PAT）的延长表明微相分离结构的表面能有效地抑制粘附血小板的活化，在离体实验（兔动静脉分流）中，嵌段共聚物的移植物的通畅时间明显长于均聚物。在均聚物制成的移植物的情况下，循环血小板的数量和功能的时程变化是显著的。另一方面，在嵌段共聚物的情况下，循环血小板的数量和功能在分流形成后维持在正常范围内。从这些结果，优良的抗血栓性和血液相容性的嵌段型共聚物被证实。在犬冠状动脉旁路移植实验中，内径为1.5mm的HEMA-St涂层人工血管可保持通畅达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.