In this study, 3D hydrogel-based vascular structures with multilevel fluidic channels (macro-channel for mechanical stimulation and microchannel for nutrient delivery and chemical stimulation) were fabricated by extrusion-based three-dimensional (3D) bioprinting, which could be integrated into organ-on-chip devices that would better simulate the microenvironment of blood vessels. In this approach, partially cross-linked hollow alginate filaments loading fibroblasts and smooth muscle cells were extruded through a coaxial nozzle and then printed along a rotated rod template, and endothelial cells were seeded into the inner wall. Because of the fusion of adjacent hollow filaments, two-level fluidic channels, including a macro-channel in the middle formed from the cylindrical template and a microchannel around the wall resulted from the hollow filaments were formed. By this method, different shapes of vessellike structures of millimeter diameter were printed. The structures printed using 4% alginate exhibited ultimate strength of 0.184 MPa, and L929 mouse fibroblasts encapsulated in the structures showed over 90% survival within 1 week. As a proof of concept, an envisioned load system of both mechanical and chemical stimulation was demonstrated. In addition, a vascular circulation flow system, a cerebral artery surgery simulator, and a cell coculture model were fabricated to demonstrate potential tissue engineering applications of these printed structures.
Keywords: 3D bioprinting; 3D cell culture; multilevel fluidic channels; tissue engineering; vascularization.