A nitric oxide releasing, self assembled peptide amphiphile matrix that mimics native endothelium for coating implantable cardiovascular devices.
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.
Kushwaha
Meenakshi
M
Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35205, USA.
Anderson
Joel M
JM
Bosworth
Charles A
CA
Andukuri
Adinarayana
A
Minor
William P
WP
Lancaster
Jack R
JR
Anderson
Peter G
PG
Brott
Brigitta C
BC
Jun
Ho-Wook
HW
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
D020099:Coated Materials, Biocompatible; D024042:Collagen Type I; D010455:Peptides; D012997:Solvents; D013501:Surface-Active Agents; D013193:Stainless Steel; D009569:Nitric Oxide