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      Vascular Response on a Novel Fibrin-Based Coated Flow Diverter

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          Abstract

          Purpose

          Due to thromboembolic complications and in-stent-stenosis after flow diverter (FD) treatment, the long-term use of dual antiplatelet treatment (DAPT) is mandatory. The tested nano-coating has been shown to reduce material thrombogenicity and promote endothelial cell proliferation in vitro. We compared the biocompatibility of coated (Derivo Heal) and non-coated (Derivo bare) FDs with DAPT in an animal model.

          Methods

          Derivo® bare ( n = 10) and Derivo® Heal ( n = 10) FD were implanted in the common carotid arteries (CCAs) of New Zealand white rabbits. One additional FD, alternately a Derivo bare ( n = 5) or Derivo Heal ( n = 5), was implanted in the abdominal aorta (AA) for assessment of the patency of branch arteries. Histopathological examinations were performed after 28 days. Angiography was performed before and after FD implantation and at follow-up.

          Results

          Statistical analysis of the included specimens showed complete endothelialization of all FDs with no significant differences in neointima thickness between Derivo® bare and Derivo® Heal (CCA: p = 0.91; AA: p = 0.59). A significantly reduced number of macrophages in the vessel wall of the Derivo Heal was observed for the CCA ( p = 0.02), and significantly reduced fibrin and platelet deposition on the surface of the Derivo Heal was observed for the AA. All branch arteries of the stented aorta remained patent.

          Conclusion

          In this animal model, the novel fibrin-based coated FD showed a similar blood and tissue compatibility as the non-coated FD.

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          Most cited references30

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          Endovascular treatment of intracranial aneurysms with flow diverters: a meta-analysis.

          Flow diverters are important tools in the treatment of intracranial aneurysms. However, their impact on aneurysmal occlusion rates, morbidity, mortality, and complication rates is not fully examined. We conducted a systematic review of the literature searching multiple databases for reports on the treatment of intracranial aneurysms with flow-diverter devices. Random effects meta-analysis was used to pool outcomes of aneurysmal occlusion rates at 6 months, and procedure-related morbidity, mortality, and complications across studies. A total of 29 studies were included in this analysis, including 1451 patients with 1654 aneurysms. Aneurysmal complete occlusion rate was 76% (95% confidence interval [CI], 70%-81%). Procedure-related morbidity and mortality were 5% (95% CI, 4%-7%) and 4% (95% CI, 3%-6%), respectively. The rate of postoperative subarachnoid hemorrhage was 3% (95% CI, 2%-4%). Intraparenchymal hemorrhage rate was 3% (95% CI, 2%-4%). Perforator infarction rate was 3% (95% CI, 1%-5%), with significantly lower odds of perforator infarction among patients with anterior circulation aneurysms compared with those with posterior circulation aneurysms (odds ratio, 0.01; 95% CI, 0.00-0.08; P<0.0001). Ischemic stroke rate was 6% (95% CI, 4%-9%), with significantly lower odds of perforator infarction among patients with anterior circulation aneurysms compared with those with posterior circulation aneurysms (odds ratio, 0.15; 95% CI, 0.08-0.27; P<0.0001). This meta-analysis suggests that treatment of intracranial aneurysms with flow-diverter devices is feasible and effective with high complete occlusion rates. However, the risk of procedure-related morbidity and mortality is not negligible. Patients with posterior circulation aneurysms are at higher risk of ischemic stroke, particularly perforator infarction. These findings should be considered when considering the best therapeutic option for intracranial aneurysms.
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            A new endoluminal, flow-disrupting device for treatment of saccular aneurysms.

            We report a preclinical study of a new endoluminal device for aneurysm occlusion to test the hypothesis that the device, even without use of intrasaccular coil placement, could occlude saccular aneurysms without causing substantial parent artery compromise or compromise of adjacent, small branch arteries. The Pipeline Neuroendovascular Device (Pipeline NED; Chestnut Medical Technologies, Inc) is a braided, tubular, bimetallic endoluminal implant aimed at occlusion of saccular aneurysms through flow disruption along the aneurysm neck. The device was implanted across the necks of 17 elastase-induced aneurysms in the New Zealand white rabbit model and followed for 1 month (n=6), 3 months (n=5), and 6 months (n=6). In each subject, a second device was implanted in the abdominal aorta to cover the origins of lumbar arteries. Aneurysm occlusion rates by angiography (grade 1, complete occlusion; grade 2, near-complete occlusion; and grade 3, incomplete occlusion) were documented. Percent area stenosis of the parent arteries was calculated. Presence of distal emboli in the downstream vessels in the parent artery and branch artery stenosis or occlusion was noted. Grades 1, 2, and 3 occlusion rates were noted in 9 (53%), 6 (35%), and 2 (12%) of 17 aneurysms, respectively, indicating an 88% rate of complete or near complete occlusion. No cases of branch artery occlusion or distal emboli in the downstream vessels of the parent artery, specifically the subclavian artery, were seen. Parent artery compromise from neointimal hyperplasia was minimal in most cases. The Pipeline NED is a trackable, bio- and hemocompatible device able to occlude saccular aneurysms with preservation of the parent artery and small, adjacent branch vessels.
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              Biological responses in stented arteries.

              Vascular walls change their dimension and mechanical properties in response to injury such as balloon angioplasty and endovascular stent implantation. Placement of bare metal stents induces neointimal proliferation/restenosis which progresses through different phases of repair with time involving a cascade of cellular reactions. These phases just like wound healing comprise distinct steps consisting of thrombosis, inflammation, proliferation, and migration followed by remodelling. It is noteworthy that animals show a rapid progression of healing after stent deployment compared with man. During stenting, endothelial cells are partially to completely destroyed or crushed along with medial wall injury and stretching promoting activation of platelets, and thrombus formation accompanied by inflammatory reaction. Macrophages and platelets play a central role through the release of cytokines and growth factors that induce vascular smooth muscle cell accumulation within the intima. Smooth muscle cells undergo complex phenotypic changes including migration and proliferation from the media towards the intima, and transition from a contractile to a synthetic phenotype; the molecular mechanisms responsible for this change are highlighted in this review. Since studies in animals and man show that smooth muscle cells play a dominant role in restenosis, drugs like rapamycin and paclitaxel have been coated on stent with polymers to allow local slow release of drugs, which have resulted in dramatic reduction of restenosis that was once the Achilles' heel of interventional cardiologists.
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                Author and article information

                Contributors
                ruben.mbe@gmail.com
                Journal
                Cardiovasc Intervent Radiol
                Cardiovasc Intervent Radiol
                Cardiovascular and Interventional Radiology
                Springer US (New York )
                0174-1551
                1432-086X
                16 December 2021
                16 December 2021
                2022
                : 45
                : 2
                : 236-243
                Affiliations
                [1 ]GRID grid.411937.9, Department of Neuroradiology, , Saarland University Hospital, ; Kirrberger Strasse, 66424 Homburg, Germany
                [2 ]GRID grid.7727.5, ISNI 0000 0001 2190 5763, Institute of Pathology, , University of Regensburg, ; Regensburg, Germany
                [3 ]GRID grid.411544.1, ISNI 0000 0001 0196 8249, Department of Thoracic, Cardiac and Vascular Surgery, , University Hospital Tuebingen, ; Tübingen, Germany
                [4 ]GRID grid.491642.c, ISNI 0000 0004 6071 9682, Acandis, ; Pforzheim, Germany
                [5 ]GRID grid.418095.1, ISNI 0000 0001 1015 3316, Institute of Macromolecular Chemistry, , Czech Academy of Sciences, ; Prague, Czech Republic
                [6 ]GRID grid.5719.a, ISNI 0000 0004 1936 9713, Institute for Biomedical Engineering, , University of Stuttgart, ; Stuttgart, Germany
                Author information
                http://orcid.org/0000-0003-1785-2675
                Article
                3007
                10.1007/s00270-021-03007-9
                8807434
                34913987
                261fbf4b-ea15-490d-8ea4-05bb96ed2f6b
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 9 June 2021
                : 4 November 2021
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100006360, Bundesministerium für Wirtschaft und Energie;
                Award ID: ZF4063703AJ8
                Award Recipient :
                Funded by: Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes (8981)
                Categories
                Laboratory Investigation
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) 2022

                Cardiovascular Medicine
                flow diverter,coating,surface modification,biocompatibility
                Cardiovascular Medicine
                flow diverter, coating, surface modification, biocompatibility

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