A novel method for generating 3D constructs with branched vascular networks using multi-materials bioprinting and direct surgical anastomosis

Abstract

Vessels pervade almost all body tissues, and significantly influence the pathophysiology of human body. Previous attempts to establish multi-scale vascular connection and function in 3D model tissues using bioprinting have had limited success due to the incoordination between cell-laden materials and stability of the perfusion channel. Here, we report a methodology to fabricate centimetre-scale vascularized soft tissue with high viability and accuracy using multi-materials bioprinting involving inks with low viscosity and a customized multistage-temperature-control printer. The tissue formed was perfused with branched vasculature with well-formed 3D capillary network and lumen, which would potentially supply the cellular components with sufficient nutrients in the matrix. Furthermore, the same methodology was applied for generating liver-like tissue with the objective to fabricate and mimic a mature and functional liver tissue, with increased functionality in terms of synthesis of liver specific proteins after in vitro perfusion and in vivo subperitoneal transplantation in mice. Moreover, to establish immediate blood perfusion, an elastic layer was printed wrapping sacrificial ink to support the direct surgical anastomosis of the carotid artery to the jugular vein. Our findings highlight the support extended by vasculature network in soft hydrogels which helps to sustain the thick and dense cellularization in engineered tissues.