Guangliang Zhang

The quality of the vascular network is key to the success of skin transplants. For skin grafts created with tissue engineering, vascularization is a critical step determining tissue survival. Pre-vascularization of bioengineered tissues is the basis for the establishment of effective high-quality vascular networks. In our study, a 3D bioprinted model was established to study the effects of mechanical stimulation on vascular tissue development. A co-culture of human dermal fibroblasts (HNDFs) and human umbilical vein endothelial cells (HUVECs), mixed with fibrin hydrogel, was confined by a polycaprolactone (PCL) frame and suspended in medium after culture. The results showed that a 3D bioprinted model to simulate the mechanical stimulation of vascular tissue development was established. Based on this, we here create a pre-vascularized tissue using 3D bioprinting and show that the vascular branches of the tissue can be controlled by confined forces created by size change of the polycaprolactone (PCL) framework (Fig. A-C). The confined force was measured. The Yes-associated protein participated in the regulation of vascular branch formation in the tissue. Moreover, a close relationship between the width of the cell-fibrin strip, the magnitude of force and the number of vascular branches in the bioprinted tissue exist (Fig. D-E). Our findings indicate that vascularization of bioengineered skin tissue is a complex and controllable process, and precise conditional control can achieve effective vascular network generation.