Abstract 4398: Native Endothelium Mimicking Self-Assembled Nanomatrix for Drug Eluting Stents
Introduction: Drug eluting stents (DES) is one of major therapeutic methods for treatment of cardiovascular diseases. However, recent reports suggest that DES has been associated with a higher risk of late thrombosis which may be related to inadequate endothelialization. Therefore, the main goal of this project is to develop the next generation of DES using a native endothelium mimicking self-assembled nanomatrix which will inhibit both restenosis and thrombosis while enhancing endothelialization from surrounding endothelium and endothelial progenitor cells circulating in the blood stream.
Results: The nanomatrix is formed by self-assembly of peptide amphiphiles (PAs) which contain a nitric oxide (NO) producing donor and an endothelial cell adhesive ligand, YIGSR along with enzyme-mediated degradable sites. NO was successfully released from the nanomatrix rapidly within 48 hours followed by sustained release over period of 30 days. The NO releasing nanomatrix demonstrated a significantly enhanced proliferation of endothelial cells (51±3 % to 67±2 %) but reduced proliferation of smooth muscle cells (35±2 % to 16±3 %) after 48 hrs of incubation. There was also a 470-fold decrease in platelet attachment on the NO releasing nanomatrix (10±3 platelets/cm2) compared to the collagen-I (4700±1100 platelets/cm2) coated surface. The NO releasing nanomatrix was coated by self-assembly onto commercial stainless 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.
Conclusion: Therefore, the nanomatrix has a great potential to improve clinical patency of DES as a coating material by enhancing endothelialization but reducing restenosis and thrombosis.