Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
WEE Solve GmbH, Auf der Burg 6, 55130 Mainz, Germany.
Int J Mol Sci. 2022 Jun 9;23(12):6432. doi: 10.3390/ijms23126432.
The biocompatibility of carrier nanomaterials in blood is largely hampered by their activating or inhibiting role on the clotting system, which in many cases prevents safe intravascular application. Here, we characterized an aqueous colloidal ethyl hydroxyethyl cellulose (EHEC) solution and tested its effect on ex vivo clot formation, platelet aggregation, and activation by thromboelastometry, aggregometry, and flow cytometry. We compared the impact of EHEC solution on platelet aggregation with biocompatible materials used in transfusion medicine (the plasma expanders gelatin polysuccinate and hydroxyethyl starch). We demonstrate that the EHEC solution, in contrast to commercial products exhibiting Newtonian flow behavior, resembles the shear-thinning behavior of human blood. Similar to established nanomaterials that are considered biocompatible when added to blood, the EHEC exposure of resting platelets in platelet-rich plasma does not enhance tissue thromboplastin- or ellagic acid-induced blood clotting, or platelet aggregation or activation, as measured by integrin αβ activation and P-selectin exposure. Furthermore, the addition of EHEC solution to adenosine diphosphate (ADP)-stimulated platelet-rich plasma does not affect the platelet aggregation induced by this agonist. Overall, our results suggest that EHEC may be suitable as a biocompatible carrier material in blood circulation and for applications in flow-dependent diagnostics.
载体制剂纳米材料在血液中的生物相容性在很大程度上受到其对凝血系统激活或抑制作用的阻碍，而在许多情况下，这会阻止其在血管内的安全应用。在这里，我们对一种水性胶体乙基羟乙基纤维素（EHEC）溶液进行了表征，并通过血栓弹性描记术、聚集测定法和流式细胞术测试了其对体外血栓形成、血小板聚集和激活的影响。我们比较了 EHEC 溶液对血小板聚集的影响与输血医学中使用的生物相容性材料（血浆代用品明胶多糖和羟乙基淀粉）的影响。我们证明，与表现出牛顿流动行为的商业产品相比，EHEC 溶液类似于人类血液的剪切稀化行为。与被认为在添加到血液中时具有生物相容性的既定纳米材料相似，EHEC 对富含血小板的血浆中静止血小板的暴露不会增强组织凝血活酶或鞣花酸诱导的血液凝结，也不会增强血小板聚集或激活，如整合素 αβ 激活和 P-选择素暴露所测量的那样。此外，将 EHEC 溶液添加到二磷酸腺苷（ADP）刺激的富含血小板的血浆中不会影响该激动剂诱导的血小板聚集。总体而言，我们的结果表明，EHEC 可能适合作为血液循环中的生物相容性载体材料，以及用于依赖流动的诊断应用。
