Laboratory of Cardiology, GIGA Institute, and Department of Cardiology, Centre Hospitalier Universitaire of Liège, University of Liège Hospital, Liège, Belgium.
Center for Education and Research on Macromolecules, CESAM Research Unit, University of Liège, Liège, Belgium.
J Thromb Haemost. 2023 Sep;21(9):2485-2498. doi: 10.1016/j.jtha.2023.05.004. Epub 2023 May 15.
Prosthetic heart valves are the only treatment for most patients with severe valvular heart disease. Mechanical valves, made of metallic components, are the most long-lasting type of replacement valves. However, they are prone to thrombosis and require permanent anticoagulation and monitoring, which leads to higher risk of bleeding and impacts the patient's quality of life.
To develop a bioactive coating for mechanical valves with the aim to prevent thrombosis and improve patient outcomes.
We used a catechol-based approach to produce a drug-releasing multilayer coating adherent to mechanical valves. The hemodynamic performance of coated Open Pivot valves was verified in a heart model tester, and coating durability in the long term was assessed in a durability tester producing accelerated cardiac cycles. Coating antithrombotic activity was evaluated in vitro with human plasma or whole blood under static and flow conditions and in vivo after surgical valve implantation in a pig's thoracic aorta.
We developed an antithrombotic coating consisting of ticagrelor- and minocycline-releasing cross-linked nanogels covalently linked to polyethylene glycol. We demonstrated the hydrodynamic performance, durability, and hemocompatibility of coated valves. The coating did not increase the contact phase activation of coagulation, and it prevented plasma protein adsorption, platelet adhesion, and thrombus formation. Implantation of coated valves in nonanticoagulated pigs for 1 month efficiently reduced valve thrombosis compared with noncoated valves.
Our coating efficiently inhibited mechanical valve thrombosis, which might solve the issues of anticoagulant use in patients and the number of revision surgeries due to valve thrombosis despite anticoagulation.
人工心脏瓣膜是大多数严重心脏瓣膜病患者的唯一治疗方法。机械瓣膜由金属部件制成，是最耐用的置换瓣膜类型。然而，它们容易发生血栓形成，需要持续抗凝和监测，这会导致更高的出血风险，并影响患者的生活质量。
开发一种用于机械瓣膜的生物活性涂层，以预防血栓形成并改善患者的预后。
我们使用儿茶酚基方法生产一种可释放药物的多层涂层，该涂层可附着于机械瓣膜。在心脏模型测试器中验证了涂覆的 Open Pivot 瓣膜的血液动力学性能，并在产生加速心脏周期的耐久性测试器中评估了长期的涂层耐久性。在静态和流动条件下的体外使用人血浆或全血以及在猪的胸主动脉中手术后植入瓣膜的体内评估了涂层的抗血栓形成活性。
我们开发了一种由替格瑞洛和米诺环素释放交联纳米凝胶与聚乙二醇共价结合组成的抗血栓形成涂层。我们证明了涂覆瓣膜的水动力性能、耐久性和血液相容性。该涂层不会增加凝血的接触相激活，并且可以防止血浆蛋白吸附、血小板黏附和血栓形成。在未抗凝的猪中植入涂层瓣膜 1 个月可有效减少瓣膜血栓形成，与未涂层瓣膜相比。
我们的涂层有效地抑制了机械瓣膜血栓形成，这可能解决了患者使用抗凝剂和因抗凝而导致的瓣膜血栓形成导致的修订手术数量的问题。
