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 sup-ply. 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 engi-neered micro-channels guides endothelial cells to form patent micro-vessels which sprouted in accor-dance with the channel orientation. Three different in-vitro models were used to demonstrate anastomo-sis 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 ap-proach proposes a new micro-fabrication strategy which introduces uncompromised micro-fluidic device geometrical accuracy at the tissue-scale level.

Automated summary

Vascularization of 3D engineered tissues is a challenge in tissue engineering. This study introduces the design and fabrication of an AngioTube, a biodegradable macro-vessel surrounded by micro-channel array, to support physiological flow distribution and integration with living capillaries. The engineered micro-channels guide endothelial cells to form patent micro-vessels, and in-vitro and in-vivo models demonstrate anastomosis with vascular networks. This approach offers a new micro-fabrication strategy with high geometrical accuracy at the tissue-scale level.