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通过纤维蛋白溶解交互式涂层增强体外膜肺氧合系统的血液相容性:使用3D微流控模型对血凝块溶解的体外评估。

Enhancing Hemocompatibility in ECMO Systems With a Fibrinolytic Interactive Coating: in Vitro Evaluation of Blood Clot Lysis Using a 3D Microfluidic Model.

作者信息

Witzdam Lena, Sandhu Samarth, Shin Suji, Hong Yeahwa, Kamal Shanzeh, Grottke Oliver, Cook Keith E, Rodriguez-Emmenegger Cesar

机构信息

Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Carrer de Baldiri Reixac, 10, 12, Barcelona, 08028, Spain.

DWI - Leibniz Institute for Interactive Materials, Forckenbeckstr. 50, 52074, Aachen, Germany.

出版信息

Macromol Biosci. 2025 May;25(5):e2400530. doi: 10.1002/mabi.202400530. Epub 2025 Jan 13.

Abstract

Blood-contacting medical devices, especially extracorporeal membrane oxygenators (ECMOs), are highly susceptible to surface-induced coagulation because of their extensive surface area. This can compromise device functionality and lead to life-threatening complications. High doses of anticoagulants, combined with anti-thrombogenic surface coatings, are typically employed to mitigate this risk, but such treatment can lead to hemorrhagic complications. Therefore, bioactive surface coatings that mimic endothelial blood regulation are needed. However, evaluating these coatings under realistic ECMO conditions is both expensive and challenging. This study utilizes microchannel devices to simulate ECMO fluid dynamics and assess the clot-lysis efficacy of a self-activating fibrinolytic coating system. The system uses antifouling polymer brushes combined with tissue plasminogen activator (tPA) to induce fibrinolysis at the surface. Here, tPA catalyzes the conversion of blood plasminogen into plasmin, which dissolves clots. This positive feedback loop enhances clot digestion under ECMO-like conditions. This findings demonstrate that this coating system can significantly improve the hemocompatibility of medical device surfaces.

摘要

与血液接触的医疗设备,尤其是体外膜肺氧合器(ECMO),由于其表面积大,极易发生表面诱导凝血。这可能会损害设备功能并导致危及生命的并发症。通常采用高剂量抗凝剂与抗血栓形成表面涂层相结合的方法来降低这种风险,但这种治疗可能会导致出血并发症。因此,需要能够模拟内皮细胞血液调节功能的生物活性表面涂层。然而,在现实的ECMO条件下评估这些涂层既昂贵又具有挑战性。本研究利用微通道装置模拟ECMO流体动力学,并评估一种自激活纤维蛋白溶解涂层系统的凝块溶解效果。该系统使用防污聚合物刷与组织纤溶酶原激活剂(tPA)相结合,在表面诱导纤维蛋白溶解。在这里,tPA催化血液纤溶酶原转化为纤溶酶,纤溶酶可溶解凝块。这种正反馈回路在类似ECMO的条件下增强了凝块消化。这些发现表明,这种涂层系统可以显著提高医疗器械表面的血液相容性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1f8/12080294/4f43293dd5bc/MABI-25-2400530-g004.jpg

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