Nojiri C, Okano T, Jacobs H A, Park K D, Mohammad S F, Olsen D B, Kim S W
Department of Pharmaceutics/Center for Controlled Chemical Delivery, University of Utah, Salt Lake City 84108.
J Biomed Mater Res. 1990 Sep;24(9):1151-71. doi: 10.1002/jbm.820240903.
HEMA/styrene (HEMA/STY) block copolymers and poly(ethylene oxide) 4,000 M.W. (PEO4K) grafted Biomer (B-PEO4K) surfaces have been synthesized, characterized, and evaluated as blood-contacting materials. These surfaces have demonstrated improved blood compatibility, compared to Biomer, in in vitro and ex vivo experiments. Biomer vascular grafts (6 mm I.D. 7 cm in length) were fabricated by a dip coating process. The luminal surface was modified either with PEO grafting, HEMA/STY coating, or Biomer coating (control). These surface-modified grafts were implanted in the abdominal aortas of dogs and evaluated for graft patency and protein adsorption. Surface protein layer thickness was measured by transmission electron microscopy (TEM). B-PEO4K and Biomer showed thick multilayers of adsorbed proteins (1000-2000 A) after 3 weeks to 1 month implantation. In contrast, HEMA/STY only showed a monolayer protein thickness (less than 200 A), even after 3 months. Visualization of adsorbed plasma proteins (albumin, IgG, and fibrinogen) was performed with scanning electron microscopy (SEM)/TEM using an immunogold double antibody technique. The pattern of protein distribution showed high concentrations of fibrinogen and IgG, and less albumin adsorbed onto Biomer and B-PEO4K. In contrast, HEMA/STY showed a patchy protein distribution pattern with high concentrations of albumin and IgG, and relatively less fibrinogen. Adsorbed monolayer patterns showed improved compatibility over multilayered proteins. The Biomer and B-PEO4K grafts occluded within 1 month, while HEMA/STY grafts were patent for over 3 months. The thin and stable adsorbed protein layer on HEMA/STY surfaces may be associated with the microdomain structures of the surface, and will play an important role in long-term in vivo blood compatibility. This manuscript will evaluate the long-term in vivo performance of these polymers, analyze the extent of protein adsorption onto the surfaces, and correlate protein layer thickness to the thrombogenicity of the polymer surfaces.
已合成、表征并评估了甲基丙烯酸羟乙酯/苯乙烯（HEMA/STY）嵌段共聚物以及接枝了聚环氧乙烷4000分子量（PEO4K）的Biomer（B-PEO4K）表面作为血液接触材料。在体外和离体实验中，与Biomer相比，这些表面已显示出改善的血液相容性。通过浸涂工艺制备了内径6mm、长度7cm的Biomer血管移植物。管腔表面用PEO接枝、HEMA/STY涂层或Biomer涂层（对照）进行修饰。将这些表面改性的移植物植入犬的腹主动脉中，并评估移植物的通畅性和蛋白质吸附情况。通过透射电子显微镜（TEM）测量表面蛋白质层厚度。植入3周后至1个月后，B-PEO4K和Biomer显示出吸附蛋白质的厚多层结构（1000 - 2000埃）。相比之下，即使在3个月后，HEMA/STY仅显示出单层蛋白质厚度（小于200埃）。使用免疫金双抗体技术通过扫描电子显微镜（SEM）/TEM对吸附的血浆蛋白（白蛋白、IgG和纤维蛋白原）进行可视化。蛋白质分布模式显示Biomer和B-PEO4K上吸附有高浓度的纤维蛋白原和IgG，白蛋白较少。相比之下，HEMA/STY显示出斑片状蛋白质分布模式，其中白蛋白和IgG浓度较高，纤维蛋白原相对较少。吸附的单层模式显示出比多层蛋白质更好的相容性。Biomer和B-PEO4K移植物在1个月内闭塞，而HEMA/STY移植物在3个月以上保持通畅。HEMA/STY表面上薄而稳定的吸附蛋白质层可能与表面的微区结构有关，并将在长期体内血液相容性中发挥重要作用。本手稿将评估这些聚合物的长期体内性能，分析蛋白质在表面上的吸附程度，并将蛋白质层厚度与聚合物表面的血栓形成性相关联。
