title: A nitric oxide releasing, self assembled peptide amphiphile matrix that mimics native endothelium for coating implantable cardiovascular devices.
abstract: 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 h, 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 h of incubation. There was also a 150-fold decrease in platelet attachment on the NO releasing nanofibrous matrix (470+/-220 platelets/cm(2)) compared to the collagen-I (73+/-22 x 10(3)platelets/cm(2)) 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.
authors.affiliation: Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35205, USA.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Kushwaha
authors.forename: Joel M
authors.initials: JM
authors.lastname: Anderson
authors.forename: Charles A
authors.initials: CA
authors.lastname: Bosworth
authors.forename: Adinarayana
authors.initials: A
authors.lastname: Andukuri
authors.forename: William P
authors.initials: WP
authors.lastname: Minor
authors.forename: Jack R
authors.initials: JR
authors.lastname: Lancaster
authors.forename: Peter G
authors.initials: PG
authors.lastname: Anderson
authors.forename: Brigitta C
authors.initials: BC
authors.lastname: Brott
authors.forename: Ho-Wook
authors.initials: HW
authors.lastname: Jun
mesh_terms: D000595:Amino Acid Sequence; D001011:Aorta / Q000166:cytology; D040761:Biomimetic Materials / Q000494:pharmacology*; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D024042:Collagen Type I / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D004727:Endothelium / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects; D057139:Nanofibers / Q000648:ultrastructure; D009569:Nitric Oxide / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects; D012997:Solvents; D013193:Stainless Steel / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D020099:Coated Materials, Biocompatible; D024042:Collagen Type I; D010455:Peptides; D012997:Solvents; D013501:Surface-Active Agents; D013193:Stainless Steel; D009569:Nitric Oxide