A micro-channel array in a tissue engineered vessel graft guides vascular morphogenesis for anastomosis with self-assembled vascular networks

Vascularization of 3D engineered tissues poses a great challenge in the field of tissue engineering. One promising approach for vascularizing engineered tissue is cocultivation with endothelial cells (ECs), which spontaneously self-assemble into a natural capillary network in the presence of supportive cells. However, the ECs do not self-assemble according to physiological hierarchy which is required to support blood supply. This work describes the design and fabrication of an AngioTube, a biodegradable engineered macro-vessel surrounded by cylindrical micro-channel array, which is designed to support physiological flow distribution and enable the integration with living capillaries. The well-defined geometry of the engineered micro-channels guides endothelial cells to form patent micro-vessels which sprouted in accordance with the channel orientation. Three different in-vitro models were used to demonstrate anastomosis of these engineered micro-vessels with self-assembled vascular networks. Finally, in-vivo functionality was demonstrated by direct anastomosis with the femoral artery in a rat hindlimb model. This unique approach proposes a new micro-fabrication strategy which introduces uncompromised micro-fluidic device geometrical accuracy at the tissue-scale level. Statement of significance: This study proposes a micro-fabrication strategy suitable for processing real-scale cylindrical implants with very high accuracy, which will enable translation of the high-resolution geometry of micro-fluidic devices to clinically relevant implants containing functional multi-scale vascular networks. Moreover, this approach promises to advance the field of tissue engineering by opening new opportunities to explore the impact of well controlled and uncompromised 3D micro-geometry on cellular behavior.