Coaxial Electrohydrodynamic Bioprinting of Pre-vascularized Cell-laden Constructs for Tissue Engineering

Recapitulating the vascular networks that maintain the delivery of nutrition, oxygen, and byproducts for the living cells within the three-dimensional (3D) tissue constructs is a challenging issue in the tissue-engineering area. Here, a novel coaxial electrohydrodynamic (EHD) bioprinting strategy is presented to fabricate thick pre-vascularized cell-laden constructs. The alginate and collagen/calcium chloride solution were utilized as the outer-layer and inner-layer bioink, respectively, in the coaxial printing nozzle to produce the core-sheath hydrogel filaments. The effect of process parameters (the feeding rate of alginate and collagen and the moving speed of the printing stage) on the size of core and sheath lines within the printed filaments was investigated. The core-sheath filaments were printed in the predefined pattern to fabricate lattice hydrogel with perfusable lumen structures. Endothelialized lumen structures were fabricated by culturing the core-sheath filaments with endothelial cells laden in the core collagen hydrogel. Multilayer core-sheath filaments were successfully printed into 3D porous hydrogel constructs with a thickness of more than 3 mm. Finally, 3D pre-vascularized cardiac constructs were successfully generated, indicating the efficacy of our strategy to engineer living tissues with complex vascular structures.