Facile endothelium protection from TNF-α inflammatory insult with surface topography

Publication date: September 2017
Source:Biomaterials, Volume 138
Author(s): Georgios Stefopoulos, Costanza Giampietro, Volkmar Falk, Dimos Poulikakos, Aldo Ferrari
Adverse events triggered by the direct contact between blood and synthetic materials constitute a sincere shortcoming of cardiovascular implant technology. A well-connected autologous endothelium, generated through the process of endothelialization, impedes such interaction and endows the implant luminal interface with optimal protection. The endothelialization of artificial substrates is the result of a complex interplay between endothelial cells (ECs), surface topography, and flow-generated wall shear stress (WSS). This is however tainted by the pro-inflammatory signaling, typical of cardiovascular patients, which compromises endothelial integrity and survival. Here, we challenge human endothelial monolayers with the pro-inflammatory factor TNF-α under realistic WSS conditions. In these experimental settings we demonstrate that the simple contact between ECs and an optimized surface geometry can inhibit NF-kB activation downstream of TNF-α yielding increased stability of VE-Cadherin mediated cell-to-cell junctions and of focal adhesions. Therefore the here-presented topographic modification can be implemented on a range of artificial substrates enabling their endothelialization under supra-physiological flow and in the presence of pro-inflammatory insults. These new findings constitute an important step toward achieving the full hemocompatibility of cardiovascular implants.



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