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首页> 外文期刊>Journal of biomedical materials research. Part B, Applied biomaterials. >Water-soluble argatroban for antithrombogenic surface coating of tissue-engineered cardiovascular tissues
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Water-soluble argatroban for antithrombogenic surface coating of tissue-engineered cardiovascular tissues

机译：水溶性argatroban用于组织工程化的心血管组织的抗血栓形成表面涂层

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Argatroban is a powerful synthetic anticoagulant, but due to its water-insoluble nature, it is unsuitable for use as a coating material to reduce the thrombogenic potential of natural or tissue-engineered blood-contacting cardiovascular tissues. On the other hand, anionic compounds could adsorb firmly onto connective tissues. Therefore, in this study, an anionic form of argatroban was prepared by neutralization from its alkaline solution, dialysis, and freeze-drying. The subsequently obtained argatroban derivative could be easily dissolved in water. Analysis of the surface chemical composition showed that the water-soluble argatroban (WSA) could be adsorbed on the entire surface of tissue-engineered connective tissue sheets composed mainly of collagen. Adsorption was achieved on immersion of the tissue-engineered connective tissue sheet in a saline/WSA solution for only 30 s without any change in the mechanical properties of the tissue-engineered sheets. Complete surface adsorption (ca., 1 mg/cm~2) was obtained at WSA concentrations of over 5 mg/mL. WSA adsorption was maintained for at least 7 days with rinsing. Blood coagulation was significantly prevented on the WSA-adsorbed surfaces in acute in vitro experiments. The coating was applied to in vivo tissue-engineered vascular grafts (biotubes) or tri-leaflet tissues (biovalves) under development, ensuring a high likelihood of nonthrombogenicity of their blood-contacting surfaces with high patency, at least in the sub-chronic phase. It appears that WSA satisfies the initial requirements for a biocompatible aqueous coating material for use in natural or tissue-engineered tissues.
机译：Argatroban是一种强大的合成抗凝剂，但由于其不溶于水的特性，因此不适合用作涂料，以减少天然或组织工程化的血液接触性心血管组织的血栓形成潜能。另一方面，阴离子化合物可以牢固地吸附在结缔组织上。因此，在这项研究中，通过从碱性溶液中和，透析和冷冻干燥制得了阴离子形式的阿加曲班。随后获得的阿加曲班衍生物可以容易地溶于水中。表面化学成分分析表明，水溶性阿加曲班（WSA）可以吸附在主要由胶原蛋白组成的组织工程结缔组织片的整个表面上。将组织工程化的结缔组织薄片浸入盐水/ WSA溶液中仅30 s即可实现吸附，而组织工程化的薄片的机械性能没有任何变化。在WSA浓度超过5 mg / mL时获得完全的表面吸附（约1 mg / cm〜2）。漂洗保持WSA吸附至少7天。在急性体外实验中，明显抑制了WSA吸附表面的凝血。该涂层被应用于正在发育中的体内组织工程化血管移植物（生物管）或三叶组织（生物瓣膜），确保至少在亚慢性期具有高通畅性的血液接触表面非血栓形成的可能性很高。 。似乎WSA满足了用于自然或组织工程组织的生物相容性水性涂料的初始要求。

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