Autor: |
Hwang PTJ; Endomimetics, LLC, Birmingham, Alabama 35242, United States.; Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, Alabama 35294, United States., Sherwood JA; Endomimetics, LLC, Birmingham, Alabama 35242, United States., Millican RC; Endomimetics, LLC, Birmingham, Alabama 35242, United States., Bobba PS; Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, Alabama 35294, United States., Lynd TO; Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, Alabama 35294, United States., Garner JN; Endomimetics, LLC, Birmingham, Alabama 35242, United States., Brott BC; Endomimetics, LLC, Birmingham, Alabama 35242, United States.; Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama 35294, United States., Hou D; Boston Scientific, Marlborough, Massachusetts 01752, United States., Jun HW; Endomimetics, LLC, Birmingham, Alabama 35242, United States.; Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, Alabama 35294, United States. |
Abstrakt: |
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 vitro . In addition, the nanomatrix coating promoted endothelial cell proliferation and reduced platelet adhesion compared to the uncoated device membranes in vitro . 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 in vitro and in vivo 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. |