Evaluation of the effect of expansion and shear stress on a self-assembled endothelium mimicking nanomatrix coating for drug eluting stents in vitro and in vivo

Abstract

Coating stability is increasingly recognized as a concern impacting the long-term effectiveness of drug eluting stents (DES). In particular, unstable coatings have been brought into focus by a recent published report (JAMA 2012). Towards the goal of overcoming current challenges of DES performance, we have developed an endothelium mimicking nanomatrix coating composed of peptide amphiphiles that promote endothelialization, but limit smooth muscle cell proliferation and platelet adhesion. Here, we report a novel water evaporation based method to uniformly coat the endothelium mimicking nanomatrix onto stents using a rotational coating technique, thereby eliminating residual chemicals and organic solvents, and allowing easy application to even bioabsorbable stents. Furthermore, the stability of the endothelium mimicking nanomatrix was analyzed after force experienced during expansion and shear stress under simulated physiological conditions. Results demonstrate uniformity and structural integrity of the nanomatrix coating. Preliminary animal studies in a rabbit model showed no flaking or peeling, and limited neointimal formation or restenosis. Therefore, it has the potential to improve the clinical performance of DES by providing multifunctional endothelium mimicking characteristics with structural integrity on stent surfaces.

Novel Multifunctional Nanomatrix Reduces Inflammation in Dynamic Conditions in Vitro and Dilates Arteries ex Vivo

“…33–35 Our previous studies have demonstrated that our nanomatrix coating forms a stable, smooth, uniform surface on stents; this may be a critical factor in prevention of inflammatory cell adhesion. 25 Thus, the nanomatrix coating itself may be protective under flow against inflammatory cell adhesion, although the addition of NO increased this protection. To investigate the effect of NO, the dynamic adhesion assay for PA-YK-NO coated stainless steel was repeated with the addition of 100 µM carboxy-PTIO, a well-known NO scavenger.…”

“…25 Briefly, the substrate mounted on a rotating mandrel attached to a motor was immersed within PA-YK or PA-YK-NO solution contained in an open top reservoir for 12 hours. The rotation ensured uniform coating of the nanomatrix on all substrate surfaces, while the open top of the reservoir facilitated evaporation.…”

A Nitric Oxide–Releasing Self-Assembled Peptide Amphiphile Nanomatrix for Improving the Biocompatibility of Microporous Hollow Fibers

“…39 Similarly, we have demonstrated that the PA-YK-NO was stable under physiologic conditions with very little flaking or cracking, even when compared to commercial medical device coatings. 40 In this study, we showed that the biomimetic nanomatrix did not affect the gas exchange properties of the microporous hollow fibers in bench-top studies.…”

Nanomatrix Coated Stent Enhances Endothelialization but Reduces Platelet, Smooth Muscle Cell, and Monocyte Adhesion under Physiologic Conditions

“…These results also help explain the efficacy of the nanomatrix coated stent we observed in our previous preliminary in vivo rabbit iliac artery study, in which the nanomatrix-coated stent displayed reduced neointimal hyperplasia, reduced restenosis, and no evidence of thrombosis or fibrin deposition after 4 weeks. 26 Thus, these results could be translatable to in vivo settings.…”

“…24,27 Additionally, the nanomatrix is stable under physiological shear stresses, prevents and attenuates inflammatory responses, and enhances endothelial progenitor cell adhesion and differentiation. 25,26,28 In consideration of these results, it is essential to investigate the effects of nanomatrix-coated stents under physiological flow on endothelialization, smooth muscle cell migration, inflammation, and platelet adhesion.…”