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

Abstract

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.