Abstract 10174: Native Endothelium Mimicking Self-Assembled Nanomatrix for Drug-Eluting Stents
Introduction: Drug eluting stents (DES) have recently been associated with a greater risk of late thrombosis which may be due to inadequate endothelialization. Therefore, the goal of this study is to develop the next generation of DES by reconstituting a native endothelium mimicking surface using a self-assembled nanomatrix coating. This will inhibit both restenosis and thrombosis while enhancing endothelialization from surrounding endothelium and endothelial progenitor cells (EPCs) circulating in the blood stream.
Results: The nanomatrix is formed by self-assembly of peptide amphiphiles (PAs). The PAs contain a nitric oxide (NO) donor and an endothelial cell adhesive ligand, YIGSR along with enzyme-mediated degradable sites. NO was successfully released from the nanomatrix in two phases. Rapid release within 48 hours was followed by sustained release over period of 30 days. This nanomatrix demonstrated significantly enhanced endothelial cells proliferation (51 ± 3 % to 67 ± 2 %) but reduced smooth muscle cell proliferation (35 ± 2 % to 16 ± 3 %) after 48 hrs of incubation. There was also a 470-fold decrease in platelet attachment on this nanomatrix (10±3 platelets/cm2) compared to the collagen-I (4700±1100 platelets/cm2) coated surface. This NO releasing nanomatrix was coated by self-assembly onto commercial stainless steel stents, and uniform coating was characterized using SEM. Subsequently, the NO releasing nanomatrix coated stents were deployed into rabbit iliac arteries. After 4 weeks, histological analysis demonstrated uniform coverage by endothelial cells, very little neointimal hyperplasia, and no thrombus. No evidence of peeled off coatings indicated that the endothelium mimicking nanomatrix coating was stable under circulating blood and successfully prevented neointimal hyperplasia and thrombus while promoting re-endothelialization. Currently, the effect of this nanomatrix on EPCs is being assessed by studying the adhesion, migration, and differentiation of human peripheral bone marrow mononuclear cells on the NO releasing nanomatrix.
Conclusion: This nanomatrix has great potential to improve clinical patency of DES as a coating material by enhancing endothelialization but reducing restenosis and thrombosis.
- © 2010 by American Heart Association, Inc.