Endothelialization of Rationally Microtextured Surfaces with Minimal Cell Seeding Under Flow.

The generation of a confluent and functional endothelium at the luminal surface of cardiovascular devices represents the ideal solution to avoid contact between blood and synthetic materials thus allowing the long-term body integration of the implants. Due to the foreseen paucity of source cells in cardiovascular patients, surface engineering strategies to achieve full endothelialization, while minimizing the amount of endothelial cells required to seed the surface leading to prompt and full coverage with an endothelium are necessary. A stable endothelialization is the result of the interplay between endothelial cells, the flow-generated walls shear stress and the substrate topography. Here a novel strategy is designed and validated based on the use of engineered surface textures combined with confined islands of seeded endothelial cells. Upon release of the confinement, the cell island populations are able to migrate on the texture and merge under physiological flow conditions to promptly generate a fully connected endothelium. The interaction between endothelial cells and surface textures supports the process of endothelialization through the stabilization of cell-to-substrate adhesions and cell-to-cell junctions. It is shown that with this approach, when ≈50% of a textured surface is initially covered with cell seeding, the time to full endothelialization compared to an untextured surface is almost halved, underpinning the viability and effectiveness of the method for the quick and stable coverage of cardiovascular implants.