Guided assembly of endothelial cells on hydrogel matrices patterned with microgrooves: a basic model for microvessel engineering

Abstract

Engineering microvessel structures with spatial control has important implications for tissue engineering and regenerative medicine. We demonstrate a facile approach to integrate structural and biochemical patterns on biodegradable hydrogel matrices via combining soft-lithographic and micromolding techniques to enable self-assembly of endothelial cells toward vessel morphogenesis. Human umbilical cord vein endothelial cells (HUVECs), with or without stromal fibroblasts, were cultured on matrices made of hyaluronic acid–dextran or agarose hydrogels patterned with microgrooves containing entrapped collagen. It was found that only with appropriate microgroove geometry would the patterned matrices induce the aggregation and coalescence of endothelial cells to form microvessel-like structures. On the basis of the monoculture model, a co-culture configuration mimicking the natural vessel morphology was also established on the hyaluronic acid–dextran matrix, which contained double layered cellular assemblies through recruitment of fibroblasts to the surface of the pre-assembled endothelial cords. This study shows that the hydrogel matrices patterned with microgrooves provide a new and versatile system to enable the morphogenetic assembling of cells and warrant further studies for engineering microvessel tissues.