Directional migration of endothelial cells towards angiogenesis using polymer fibres in a 3D co-culture system

Abstract

Development of an in vitro prevascularized scaffold is of great importance to produce vascularization in tissue-engineered devices and for other clinical purposes. To this aim, polymer fibres covered with human umbilical vein endothelial cells (HUVECs) were used to induce directional 'angiogenesis' in a 3D co-culture system. Gelatin or RGD peptides were immobilized on surface-modified polymer fibres [100 µm diameter poly(ethylene terephthalate) monofilaments] via N-hepthylamine plasma polymer and carboxy-methyl-dextran interlayers. Fibres fully covered with HUVECs were then embedded in a fibrin gel, following a parallel alignment pattern, in the presence of fibroblasts. Tube-like structures occurred along the fibres and a network was formed between neighbouring fibres. These events were promoted with increased incubation times. Biomolecule-grafted fibres created a guidance pathway that facilitated coated endothelial cells to form lumens and, from them, sprouting processes. However, there were no significant differences between the different surface modifications on fibres in terms of promoting tube-like structures. Thus, different stages of angiogenesis can be initiated and guided using HUVECs precovered polymer fibres embedded in a soft supportive matrix, such as fibrin, which can be further applied to the development of in vitro prevascularized tissue-engineered scaffolds.