Engineered microvasculature using maskless photolithography and on-chip hydrogel patterning: a facile approach

Abstract

In vitro models of human microvasculature are increasingly used to understand blood vessel diseases and to support drug development. Most engineered models, however, are slow and labor-intensive to produce. Here, we used a single commercial digital micromirror device (DMD)-based setup for maskless photolithography to both fabricate microfluidic chips and pattern the inside of these chips with gelatin methacrylate (GelMA) hydrogels. These hydrogel scaffolds had tunable stiffness, could be generated rapidly and were suitable for forming perfusable microvasculature from human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs). When cultured in narrow channels, the hiPSC-ECs adopted a tubular morphology that was similar to capillaries in vivo, but they followed the square channel geometry in wider channels. Compartmentalization of the chips allowed co-culture of hiPSC-ECs with hiPSC-derived astrocytes, thereby increasing model complexity. Furthermore, valve-like structures could be patterned inside the channels, mimicking functional vascular valves, holding promise for thrombosis and lymphatic vasculature research.