A Nitric Oxide Releasing Self Assembled Peptide Amphiphile Matrix that Mimics Native Endothelium for Coating Implantable Cardiovascular Devices

摘要

Cardiovascular disease is the number one cause of death in the United States. Deployment of stents and vascular grafts has been a major therapeutic method for treatment. However, restenosis, incomplete endothelialization, and thrombosis hamper the long term clinical success. As a solution to meet these current challenges, we have developed a native endothelial ECM mimicking self-assembled nanofibrous matrix to serve as a new treatment model. The nanofibrous matrix is formed by self-assembly of peptide amphiphiles (PAs), which contain nitric oxide (NO) donating residues, endothelial cell adhesive ligands composed of YIGSR peptide sequence, and enzyme-mediated degradable sites. NO was successfully released from the nanofibrous matrix rapidly within 48 hours, followed by sustained release over period of 30 days. The NO releasing nanofibrous matrix 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 150-fold decrease in platelet attachment on the NO releasing nanofibrous matrix (470 ± 220 platelets/cm²) compared to the collagen-I (73 ± 22 × 10³ platelets/cm²) coated surface. The nanofibrous matrix has the potential to be applied to various cardiovascular implants as a self-assembled coating, thereby providing a native endothelial extracellular matrix (ECM) mimicking environment.