Hemocompatibility studies on a degradable polar hydrophobic ionic polyurethane (D-PHI)
Hemocompatibility studies on a degradable polar hydrophobic ionic polyurethane (D-PHI)
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DOI：
10.1016/j.actbio.2016.11.005
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发表时间：
2017-01-15
影响因子：
9.7
通讯作者：
Santerre, J. Paul
中科院分区：
文献类型：
--
作者：
Brockman, Kathryne S.;Kizhakkedathu, Jayachandran N.;Santerre, J. Paul
生物材料的血液相容性是一个复杂的过程，涉及四个关键途径，包括凝血级联，补体系统，血小板和白细胞。虽然许多研究已经解决了血液与均聚物（例如Teflon）或简单共聚物（例如Dacron）生物材料的初始接触，但相对较少关注研究包含明确定义和多种功能的复杂共聚物系统的血液凝固。本研究旨在评估含有极性、疏水性和离子域（D-PHI）独特组合的复合聚氨酯（PU）的血液相容性。这包括一项全血（WB）研究，随后进行内源性和外源性凝血途径、补体激活、血小板激活试验，并评估白细胞对血小板-生物材料相互作用的影响。在WB中的D-PHI上观察到血凝块形成的小幅增加;然而，通过内源性凝血级联没有显著增加凝血。与白蛋白包被基质（阴性对照）相比，未观察到血小板粘附显著增加，血小板活化仅极轻微增加。D-PHI显示轻度补体激活和凝血的外源性途径启动增加，沿着观察到白细胞在介导血小板-生物材料相互作用中很重要。有人提出，补体是负责激活凝血刺激白细胞产生组织因子（TF），这导致外源性途径激活。这种低水平的血液凝固在D-PHI的表面可能是必要的有益的伤口愈合的血管结构，以前已报告的这种材料。声明的重要性了解血液相容性的设备预期用于血液接触的应用是很重要的预测设备故障。血液相容性是一个复杂的参数（受至少四种不同机制的影响），可测量血液-生物材料接触导致的血栓生成和免疫系统激活水平。血液相容性的复杂性意味着均聚物不太可能解决大多数生物材料面临的凝血挑战。从工程聚氨酯获得的表面化学多样性（含有疏水性，离子和极性结构域）可导致与血液的有利相互作用。目前的研究考虑了高度官能化的聚氨酯生物材料对所有四种机制的影响，以提供这种独特材料的血液相容性和重要机制的全面体外测量。(C)2016 Acta Materialia Inc.由Elsevier Ltd.出版。保留所有权利。
Biomaterial blood compatibility is a complex process that involves four key pathways, including the coagulation cascade, the complement system, platelets, and leukocytes. While many studies have addressed the initial contact of blood with homopolymeric (e.g. Teflon) or simple copolymeric (e.g. Dacron) biomaterials, relatively less attention has been given to investigating blood coagulation with respect to complex copolymeric systems containing well defined and diverse function. The current study sought to assess the hemocompatibility of a complex polyurethane (PU) containing a unique combination of polar, hydrophobic, and ionic domains (D-PHI). This included a whole blood (WB) study, followed by tests on the intrinsic and extrinsic coagulation pathways, complement activation, platelet activation, and an assessment of the effect of leukocytes on platelet-biomaterial interactions. A small increase in blood clot formation was observed on D-PHI in WB; however, there was no significant increase in clotting via the intrinsic coagulation cascade. No significant increase in platelet adhesion and only a very slight increase in platelet activation were observed in comparison to albumin-coated substrates (negative control). D-PHI showed mild complement activation and increased initiation of the extrinsic pathway of coagulation, along with the observation that leukocytes were important in mediating platelet-biomaterial interactions. It is proposed that complement is responsible for activating coagulation by inciting leukocytes to generate tissue factor (TF), which causes extrinsic pathway activation. This low level of blood clotting on D-PHI's surface may be necessary for the beneficial wound healing of vascular constructs that has been previously reported for this material.Statement of SignificanceUnderstanding the hemocompatibility of devices intended for blood-contacting applications is important for predicting device failure. Hemocompatibility is a complex parameter (affected by at least four different mechanisms) that measures the level of thrombus generation and immune system activation resulting from blood-biomaterial contact. The complexity of hemocompatibility implies that homopolymers are unlikely to solve the clotting challenges that face most biomaterials. Diversity in surface chemistry (containing hydrophobic, ionic, and polar domains) obtained from engineered polyurethanes can lead to favourable interactions with blood. The current research considered the effect of a highly functionalized polyurethane biomaterial on all four mechanisms in order to provide a comprehensive in vitro measure of the hemocompatibility of this unique material and the important mechanisms at play. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.