Regulation of vascular branch formation in 3D bioprinted tissues using confining force

The quality of the vascular network is key to the success of skin transplants. For skin grafts prepared using a tissue engineering approach, vascularization is a critical step determining tissue survival. Prevascularization of bioengineered tissues is the basis for the effective establishment of high-quality vascular networks. Previously, we established a 3D bioprinted model to simulate the mechanical stimulation of vascular tissue development. Based on this, here, we create a prevascularized tissue using 3D bioprinting and show that the vascular branches of the tissue can be controlled by the confining forces created by changing the size of the polycaprolactone (PCL) framework. In addition, it was found that the Yes-associated protein (YAP) participates in the regulation of vascular branch formation in the tissue. A close relationship was found between the width of the cell-fibrin strip, the magnitude of the force and the number of vascular branches in the bioprinted tissue exists. Together, our findings indicate that vascularization of engineered skin tissue is a complex yet controllable process, and precise mechanical control can lead to effective vascular network generation.