A free-form patterning method enabling endothelialization under dynamic flow

Endothelialization strategies aim at protecting the surface of cardiovascular devices upon their interaction with blood by the generation and maintenance of a mature monolayer of endothelial cells. Rational engineering of the surface micro-topography at the luminal interface provides a powerful access point to support the survival of a living endothelium under the challenging hemodynamic conditions created by the implant deployment and function. Surface structuring protocols must however be adapted to the complex, non-planar architecture of the target device precluding the use of standard lithographic approaches. Here, a novel patterning method, harnessing the condensation and evaporation of water droplets on a curing liquid elastomer, is developed to introduce arrays of microscale wells on the surface of a biocompatible silicon layer. The resulting topographies support the in vitro generation of mature human endothelia and their maintenance under dynamic changes of flow direction or magnitude, greatly outperforming identical, but flat substrates. The structuring approach is additionally demonstrated on non-planar interfaces yielding comparable topographies. The intrinsically freeform patterning is therefore compatible with a complete and stable endothelialization of complex luminal interfaces in cardiovascular implants