Abstract 4928: Natural Endothelium Mimicking Self-Assembled Nanomatrix for Drug Eluting Stent Applications
Deployment of stents has been a major therapeutic method for treatment of cardiovascular diseases. However, poor endothelialization and intimal hyperplasia in bare metal stents lead to restenosis. Drug eluting stents (DES) are designed to deliver therapeutic drugs to prevent intimal hyperplasia and have been implanted in about 6 million patients for last three years. However, recent reports suggest that DES have 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 natural 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. The nanomatrix is formed by self-assembly of peptide amphiphiles (PAs) which contain nitric oxide (NO) producing donors and endothelial cell adhesive ligand YIGSR along with enzyme-mediated degradable sites. Successful synthesis of PAs and the self-assembly of the PAs into nanofibers with the diameter of 8 nm forming the nanomatrix were characterized by MALDI-TOF mass spectrometry and transmission electron microscope, respectively. The nanomatrix showed significantly greater attachment and spreading of human umbilical vein endothothelial cells (HUVECs) compared to human aortic smooth muscle cells (AoSMCs). The nanomatrix was reacted with NO solution and NO was released from the nanomatrix rapidly within 24 hours followed by sustained release over period of 5 days. The NO releasing nanomatrix demonstrated a significantly enhanced proliferation of HUVECs (51 ± 3 % to 67 ± 2 %) but reduced proliferation of AoSMCs (35 ± 2 % to 16 ± 3 %) after 48 hrs of incubation. Platelet attachment on the nanomatrix is under investigation. A natural endothelium mimicking nanomatrix was successfully synthesized and supported growth of endothelial cells while inhibiting growth of smooth muscle cells. Therefore this nanomatrix could have a great potential to improve clinical patency of DES as a coating material by enhancing endothelialization but reducing restenosis.