Sulfonate Groups and Saccharides as Essential Structural Elements in Heparin-Mimicking Polymers Used as Surface Modifiers: Optimization of Relative Contents for Antithrombogenic Properties
Sulfonate Groups and Saccharides as Essential Structural Elements in Heparin-Mimicking Polymers Used as Surface Modifiers: Optimization of Relative Contents for Antithrombogenic Properties
复制标题
磺酸基和糖类作为表面改性剂的类肝素聚合物的基本结构元素：抗血栓形成特性相对含量的优化
DOI：
10.1021/acsami.7b16723
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发表时间：
2018-01-10
影响因子：
9.5
通讯作者：
Brash, John L.
中科院分区：
文献类型：
--
作者：
Chen, Xianshuang;Gu, Hao;Brash, John L.
血液相容性是生物材料研究中一个长期追求的目标，但仍然是一个难以捉摸的目标，尽管在这一领域进行了广泛的工作，但材料特性与血液反应（如凝血和血栓形成）之间的关系仍然没有明确的信息。用模拟肝素聚合物修饰的材料已经显示出前景，确实可以被视为与用肝素本身修饰的材料相媲美。在这项工作中，肝素被定义为由两个主要结构元素组成：含糖和含磺酸的单元，并基于这一概念开发了聚合物。采用聚合的方法在乙烯基功能化聚氨酯（PU）表面接枝聚合了含糖基的2-甲基丙烯酰胺葡萄糖醛酸和含磺酸基的4-乙烯基苯磺酸钠共聚物。这种接枝聚合方法简单，通过调节单体的投料比可以调节糖和磺酸的含量。仅含磺酸基或糖基的均聚物接枝材料对血小板粘附、血管内皮细胞粘附与增殖、平滑肌细胞粘附与增殖等细胞表面相互作用有不同的影响。共聚物接枝材料显示出由于磺酸和糖元素对血液反应的影响，最佳组成是磺酸与糖单位的2:1比例（材料命名为PU-PS1M1）。在细胞粘附实验中，该材料的血小板和人脐静脉平滑肌细胞密度最低，人脐静脉内皮细胞密度最高。在所研究的材料中，PU-PS1M1的血浆凝固时间也最长。因此，这种材料被证明是多功能的，具有多种特性，表明在血液接触中具有抗血栓行为。
Blood compatibility is a long sought-after goal in biomaterials research, but remains an elusive one, and in spite of extensive work in this area, there is still no definitive information on the relationship between material properties and blood responses such as coagulation and thrombus formation. Materials modified with heparin-mimicking polymers have shown promise and indeed may be seen as comparable to materials modified with heparin itself. In this work, heparin was conceptualized as consisting of two major structural elements: saccharide- and sulfonate-containing units, and polymers based on this concept were developed. Copolymers of 2-methacrylamido glucopyranose, containing saccharide groups, and sodium 4-vinylbenzenesulfonate, containing sulfonate groups, were graft-polymerized on vinyl-functionalized polyurethane (PU) surfaces by polymerization. This graft polymerization method is simple, and the saccharide and sulfonate contents are tunable by regulating the feed ratio of the monomers. Homopolymer-grafted materials, containing only sulfonate or saccharide groups, showed different effects on cell surface interactions including platelet adhesion, adhesion and proliferation of vascular endothelial cells, and adhesion and proliferation of smooth muscle cells. The copolymer-grafted materials showed effects due to both sulfonate and saccharide elements with respect to blood responses, and the optimum composition was obtained at a 2:1 ratio of sulfonate to saccharide units (material designated as PU-PS1M1). In cell adhesion experiments, this material showed the lowest platelet and human umbilical vein smooth muscle cell density and the highest human umbilical vein endothelial cell density. Among the materials investigated, PU-PS1M1 also had the longest plasma clotting time. This material was thus shown to be multifunctional with a combination of properties, suggesting thromboresistant behavior in blood contact.