Construction of multi-scale vascular chips and modelling of the interaction between tumours and blood vessels

Abstract

Despite the substantial progress in the construction of vascular structures in the past few years, building a whole blood circulatory system model containing both large vessels and capillaries inside cell-laden hydrogels remains a big challenge. Here, we present a flexible and novel process to construct a hydrogel-based microfluidic chip with such a multi-scale network by combining high-resolution three-dimensional (3D) printing and a twice-crosslinking strategy. The whole process includes: (1) vascular system design (from arteries and capillaries to veins), (2) template printing (ultrafine fiber network), (3) hydrogel material casting (formation of partially-crosslinked hydrogel sheets), (4) template peeling off (creation of microgrooves on the surfaces of the hydrogel sheets), (5) hydrogel sheet bonding (formation of a closed channel network) and (6) cell loading (specific cells seeded onto specific positions mimicking in vivo conditions). We demonstrated that it is easy to fabricate the ubiquitous structures of biological vascular systems, highly-branched networks, spiral vessels, stenosis, etc. The endothelial cell (EC) channels exhibit representative vascular functions. As a proof of concept, a bulk breast tumor tissue with a functional vascular network was built. Additionally, a vascular–tumour co-culture concept has been proposed and constructed through the process to investigate the interaction between tumours and blood vessels. The proposed strategy can also be applied to help engineer diverse meaningful in vitro models for extensive biomedical applications, from physiology and disease study to therapy evaluation.