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.
Bibliographical noteFunding Information:
This study was supported by NIH T-32 Cardiovascular Pathophysiology Training Fellowship (5T32HL007918-17 to G.A.), Alabama EPSCoR GRSD Fellowship (to G.A.), NIDDK (1DP3DK094346-01 to Y.Y. and H. J.), NHLBI (1R01HL125391-01 to H.J.), NSF Career Award (CBET-0952974 to H.J.), NIBIB (1R03EB017344-01 to H.J.), NINDS (1R43NS095455-01 to B.B. and H.J.), the American Diabetes Association (1-09-JF-33; 1-12-BS-99 to J.K), American Heart Association (13GRNT17220057 to J.K), UAB diabetes research center sponsored pilot and feasibility program supported by National Institutes of Health (P30 DK-079626), UAB Comprehensive Diabetes Center, and in part by a grant to the University of Alabama at Birmingham from the Howard Hughes Medical Institute through the Med into Grad Initiative.
All Science Journal Classification (ASJC) codes
- Materials Science(all)