共价键合多层肝素薄膜修饰涂有硅橡胶的人工血管

报道一种采用医用硅橡胶涂层作软支撑共价键合多层肝素薄膜修饰人工血管等生物医学装置使其表面具有抗凝血性能的方法. 该项技术首先在人工血管的表面上涂上医用硅橡胶作为软支撑, 再在硅橡胶涂层的表面上涂上全氟磺酸(Nafion), 为接下来的层层静电组装提供活性基团. 然后将带正电荷的二苯胺重氮树脂(PA)和带负电荷的肝素分子(Hep)通过静电吸引作用交替沉积到全氟磺酸涂层的表面上. 紫外可见吸收光谱和傅立叶红外光谱数据表明, 在紫外光照射下, 重氮树脂的重氮基团与肝素的硫酸基团之间发生光化学反应, 生成硫酸酯, 使膜内层间离子键转变成共价键, 从而使肝素多层膜的稳定性大大提高. 研究表明经层层自组装和光化学反应后肝素分子呈现良好的抗凝血性能. 人工血管肝素化表面中的肝素分子以壁面结合的方式存在, 在人工血管表面固化肝素和抗凝血酶-III (AT-III)形成的络合物显示出较好的抗凝血性. 硅橡胶涂层使肝素分子与人工血管表面有一定距离, 有利于提高抗凝血性能. 在四个双层之内, 肝素对凝血酶失活的影响随着PA/Hep双层数目增加而增加, 说明了只有最外层的肝素才对凝血酶失活有直接影响. 该方法操作工艺简单, 重复性好, 可较广泛地适用于在多种生物医用装置和多孔组织工程支架材料的表面制备稳定的抗凝血涂层, 具有良好的应用前景.

Covalently-attached Heparin Multilayer Coatings on the Luminal Surface of Silicone-coated Vascular Graft

The microporous expanded polytetrafluoroethylene (ePTFE) vascular grafts were coated using silicone as a soft support by flowing through the lumen of the graft, followed by post-coating with a second thin film consisting of Nafion. The sulfonic head groups within pendant chains of Nafion created “anchor” sites for the formation of additional multilayers of a photosensitive crosslinker amine polymer (PA) and heparin (Hep) via electrostatic interaction on the Nafion coatings. After drying, multilayers of PA/Hep were then fixed by a covalent bonding via photoreaction between heparin and the crosslinker without compromising its catalytic capacity to promote antithrombin III-mediated thrombin inactivation. Compared with ionically attached multilayers of PA/Hep, the stability of the covalently attached PA/Hep was improved greatly. The technique is robust, cheap and environmentally friendly. Thus, photocrosslinking heparin multilayers appear to be a good candidate for coating medical devices of almost any kind and any shape.