Interfacial self-assembly of endothelial cells toward angiogenic network formation in the composite hydrogel culture systems

Abstract

Fabrication of a pre-vascularized tissue in vitro is an extensive research activity. The idea behind this approach is that a network of newly formed micro-vessels may be engineered in vitro by the seeding of a scaffold with endothelial cells. To this aim, understanding the effect of physicochemical properties of the scaffolding material and the method of cell seeding, in regulating endothelial cells’ behavior in the in vitro constructs, is an emerging requirement. In this study, the effect of interfacial self-assembly and contact guidance for the endothelial cell behavior and angiogenic network formation have been studied. This has been done by the fabrication of in vitro three-dimensional tissue constructs, using multilayer surface-modified polymer fibers, and two different methods of cell seeding by human umbilical vein endothelial cells. In the first method, human umbilical vein endothelial cells, fibers, and fibrin gel matrix were combined simultaneously. In the second method, the human umbilical vein endothelial cells and fibers, having various surface coatings, were sandwiched between two layers of fibrin gel matrix with or without fibroblast cell monolayer over the fibrin gel. In the optimal conditions, the effect of fibers in conjunction with the interfacial self-assembly enhanced a tube-like and interconnected network structure formation. This design could therefore have a major impact in the generation of the pre-vascularized tissue-engineered constructs.