4D Printing of Bioartificial, Small‐Diameter Vascular Grafts with Human‐Scale Characteristics and Functional Integrity

Abstract

AbstractA novel developed 4D bioprinting technique is used for the manufacturing of human‐scale, small‐diameter vascular grafts. Accordingly, a bio‐ink is synthesized from a hybrid molecule containing sodium alginate (SA) and collagen peptide (COP). Endothelial progenitor cells (EPC) isolated from human whole blood are integrated into the bioartificial vascular graft as an autologous cell source. Likewise, human umbilical vein endothelial cells (HUVEC) are used as experimental standard. The evolving vascular grafts are printed by a customized 4D bioprinter into CaCl2 support medium for rapid cross‐linking inducing the temporospatial shaping of the grafts. After culturing for 21 days, histological and ultrastructural analyses of the bioartificial vascular grafts reveal a well‐organized matrix with imbedded EPC or HUVEC. Live‐3D‐cell–imaging and cell viability assays demonstrate a multitude of vital and metabolically active cells. Biomechanics of the grafts are proven to be comparable to human saphenous veins. Coagulation analysis reveals low thrombogenicity and high functional integrity of the vascular grafts. Surgical implantation of the grafts in a perfused cadaver model can be performed effectively and without technical issues. Finally, the current study describes for the first time the 4D bioprinting and characterization of a small‐diameter, human‐scale vascular graft for putative clinical translation.