Endomimetics, LLC, Birmingham, Alabama 35242, United States.
Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, Alabama 35294, United States.
ACS Appl Bio Mater. 2021 Jun 21;4(6):4917-4924. doi: 10.1021/acsabm.1c00202. Epub 2021 Jun 1.
Blood clots (90%) originate from the left atrial appendage (LAA) in non-valvular atrial fibrillation patients and are a major cause of embolic stroke. Long-term anticoagulation therapy has been used to prevent thrombus formation, but its use is limited in patients at a high risk for bleeding complications. Thus, left atrial appendage closure (LAAC) devices for LAA occlusion are well-established as an alternative to the anticoagulation therapy. However, the anticoagulation therapy is still required for at least 45 days post-implantation to bridge the time until complete LAA occlusion by neoendocardium coverage of the device. In this study, we applied an endothelium-mimicking nanomatrix to the LAAC device membrane for delivery of nitric oxide (NO) to enhance endothelialization, with the goal of possibly being able to reduce the duration of the anticoagulation therapy. The nanomatrix was uniformly coated on the LAAC device membranes and provided sustained release of NO for up to 1 month . In addition, the nanomatrix coating promoted endothelial cell proliferation and reduced platelet adhesion compared to the uncoated device membranes . The nanomatrix-coated and uncoated LAAC devices were then deployed in a canine LAA model for 22 days as a pilot study. All LAAC devices were not completely covered by neoendocardium 22 days post-implantation. However, histology image analysis showed that the nanomatrix-coated LAAC device had thicker neoendocardium coverage compared to the uncoated device. Therefore, our and results indicate that the nanomatrix coating has the potential to enhance endothelialization on the LAAC device membrane, which could improve patient outcomes by shortening the need for extended anticoagulation treatment.
血栓(90%)来源于非瓣膜性心房颤动患者的左心耳(LAA),是栓塞性中风的主要原因。长期抗凝治疗已被用于预防血栓形成,但在出血并发症风险较高的患者中,其应用受到限制。因此,左心耳封堵(LAAC)装置用于 LAA 闭塞已被确立为抗凝治疗的替代方法。然而,在新心内膜完全覆盖装置之前,仍需要至少 45 天的抗凝治疗来桥接时间。在这项研究中,我们将内皮模拟纳米基质应用于 LAAC 装置膜,以输送一氧化氮(NO)来增强内皮化,目的是可能减少抗凝治疗的持续时间。纳米基质均匀涂覆在 LAAC 装置膜上,可持续释放一氧化氮长达 1 个月。此外,与未涂层装置膜相比,纳米基质涂层可促进内皮细胞增殖并减少血小板黏附。然后,将纳米基质涂层和未涂层的 LAAC 装置在犬的 LAA 模型中植入 22 天作为试点研究。所有 LAAC 装置在植入后 22 天都没有被新心内膜完全覆盖。然而,组织学图像分析表明,与未涂层装置相比,纳米基质涂层的 LAAC 装置具有更厚的新心内膜覆盖。因此,我们的和结果表明,纳米基质涂层具有增强 LAAC 装置膜内皮化的潜力,通过缩短对延长抗凝治疗的需求,改善患者的预后。