title: Novel Multifunctional Nanomatrix Reduces Inflammation in Dynamic Conditions in Vitro and Dilates Arteries ex Vivo.
abstract: Inflammatory responses play a critical role in tissue-implant interactions, often limiting current implant utility. This is particularly true for cardiovascular devices. Existing stent technology does little to avoid or mitigate inflammation or to influence the vasomotion of the artery after implantation. We have developed a novel endothelium-mimicking nanomatrix composed of peptide amphiphiles that enhances endothelialization while decreasing both smooth muscle cell proliferation and platelet adhesion. Here, we evaluated whether the nanomatrix could prevent inflammatory responses under static and physiological flow conditions. We found that the nanomatrix reduced monocyte adhesion to endothelial cells and expression of monocyte inflammatory genes (TNF-α, MCP-1, IL-1β, and IL-6). Furthermore, the nitric-oxide releasing nanomatrix dramatically attenuated TNF-α-stimulated inflammatory responses as demonstrated by significantly reduced monocyte adhesion and inflammatory gene expression in both static and physiological flow conditions. These effects were abolished by addition of a nitric oxide scavenger. Finally, the nanomatrix stimulated vasodilation in intact rat mesenteric arterioles after constriction with phenylephrine, demonstrating the bioavailability and bioactivity of the nanomatrix, as well as exhibiting highly desired release kinetics. These results demonstrate the clinical potential of this nanomatrix by both preventing inflammatory responses and promoting vasodilation, critical improvements in stent and cardiovascular device technology.
authors: Grant C
authors: GC
authors: Alexander
authors: Jeremy B
authors: JB
authors: Vines
authors: Patrick
authors: P
authors: Hwang
authors: Teayoun
authors: T
authors: Kim
authors: Jeong-a
authors: JA
authors: Kim
authors: Brigitta C
authors: BC
authors: Brott
authors: School of Medicine, Division of Cardiology, Emory University , Atlanta, Georgia 30322, United States.|Severance Biomedical Science Institute, Yonsei University College of Medicine , Seoul, Korea.
authors: Young-Sup
authors: YS
authors: Yoon
authors: Ho-Wook
authors: HW
authors: Jun
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control*; D009000:Monocytes / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D053761:Nanocomposites / Q000737:chemistry / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010973:Platelet Adhesiveness / Q000187:drug effects; D051381:Rats; D015607:Stents / Q000009:adverse effects*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D010455:Peptides; D009569:Nitric Oxide
keywords: bioreactor; endothelium; inflammation; nanomatrix; stent; vasodilation