Abstract 314: Development of a Nanotube-coated Nitinol Stent for Delivery of Resolvin D1

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Phin-Peng Lee ◽  
Anuran Chatterjee ◽  
Bian Wu ◽  
Harald Nuhn ◽  
Tejal Desai ◽  
...  

Introduction: As part of a Vascular Innovation and Therapeutic Advances (VITA) contract from NHLBI, we sought to optimize a nitinol drug eluting stent to deliver a novel bioactive lipid mediator Resolvin D1 (RvD1). Methods: Nitinol stents were secured as the anode in an ethylene glycol-based anodization setup to create nanotubes on the stent surface. Scanning electron microscopy was used to evaluate the quality of the coatings where an iterative process was utilized to optimize anodization conditions (70V, 5min). To ascertain structural integrity of the coatings, stents were observed under SEM after compression in a crimping device followed by self-expansion. Nanotube-coated (NT) and unmodified bare metal (BM) nitinol stents were loaded with RvD1 by dip-coating (with sonication) followed by hanging drop evaporation of RvD1 (in ethanol). Stents were eluted in media and RvD1 levels were analyzed by EIA. An ex vivo model of vascular stent implantation was created using a 3D printer and RvD1 delivery to the vessel wall (segment of rabbit aorta) and circulating flow medium was quantified after 3 hrs of stent implantation. Results: NT stents released significant amounts of RvD1 (1273ng cumulative at day 9), where 1177ng (± 238) of RvD1 was released within 3hr and 0.111ng (± 0.014) of RvD1 was released between day 7 and day 9. Net amount of RvD1 released was 0.2nM - 2000nM, which is physiologically relevant and within the milestone goal. NT stents released much higher levels of RvD1 (9.7 pg/mg vessel; ±1.39) to the vessel wall compared to standard BM stent controls (3.9 pg/mg vessel; ±2.0) and native vessel (1.3 pg/mg vessel; ±0.5). Conclusion: We have developed optimized anodization conditions for creating a uniform coating of titania nanotubes on nitinol stents that is able to survive crimping and self-expansion. NT stents demonstrate improved loading and elution of the lipid mediator RvD1 in an ex-vivo artery flow model.

2015 ◽  
Vol 66 (15) ◽  
pp. B144
Author(s):  
Masahiko Shibuya ◽  
Kenichi Fujii ◽  
Hiroyuki Hao ◽  
Kenji Kawai ◽  
Takahirio Imanaka ◽  
...  

2018 ◽  
Vol 83 (1) ◽  
pp. 193-197 ◽  
Author(s):  
Masahiko Shibuya ◽  
Kenichi Fujii ◽  
Hiroyuki Hao ◽  
Takahiro Imanaka ◽  
Ten Saita ◽  
...  

2014 ◽  
Vol 15 (7) ◽  
pp. 800-809 ◽  
Author(s):  
D. De Cock ◽  
J. Bennett ◽  
G. J. Ughi ◽  
C. Dubois ◽  
P. Sinnaeve ◽  
...  

1994 ◽  
Vol 71 (01) ◽  
pp. 147-153 ◽  
Author(s):  
Siw Frebelius ◽  
Ulf Hedin ◽  
Jesper Swedenborg

SummaryThe thrombogenicity of the vessel wall after endothelial denudation is partly explained by an impaired inhibition of thrombin on the subendothelium. We have previously reported that thrombin coagulant activity can be detected on the vessel wall after balloon injury in vivo. The glycosaminoglycans of the subendothelium differ from those of the endothelium and have a lower catalyzing effect on antithrombin III, but inhibition of thrombin can still be augmented by addition of antithrombin III to the injured vessel surface.In this study the effect of antithrombin III and heparin on thrombin coagulant activity on the vessel wall was studied after in vivo balloon injury of the rabbit aorta using biochemical and immunohistochemical methods and thrombin was analysed after excision of the vessel. Continuous treatment with heparin, lasting until sacrifice of the animal, or treatment with antithrombin III resulted in significant reduction of thrombin coagulant activity on the injured aorta. Heparin given only in conjunction with the injury did not prevent thrombin coagulant activity or deposition of fibrin on the surface.The capacity of the injured vessel wall to inhibit thrombin in vitro was improved on aortic segments obtained from animals receiving antithrombin III but not from those given heparin. It is concluded that treatment with antithrombin III interferes with thrombin appearance on the vessel wall after injury and thereby reduces the risk for thrombosis.


Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 671
Author(s):  
Ana Osuna ◽  
Anna Ulldemolins ◽  
Hector Sanz-Fraile ◽  
Jorge Otero ◽  
Núria Farré ◽  
...  

This paper describes the design, construction and testing of an experimental setting, making it possible to study the endothelium under different pathophysiological conditions. This novel experimental approach allows the application of the following stimuli to an ex vivo vessel in a physiological bath: (a) a realistic intravascular pressure waveform defined by the user; (b) shear stress in the endothelial layer since, in addition to the pressure waveform, the flow through the vessel can be independently controlled by the user; (c) conditions of hypo/hyperoxia and hypo/hypercapnia in an intravascular circulating medium. These stimuli can be applied alone or in different combinations to study possible synergistic or antagonistic effects. The setting performance is illustrated by a proof of concept in an ex vivo rabbit aorta. The experimental setting is easy to build by using very low-cost materials widely available. Online Supplement files provide all the technical information (e.g., circuits, codes, 3D printer drivers) following an open-source hardware approach for free replication.


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