Forces and Regulation of Vascular Network

Vascularization remains one of the main challenge in the field of tissue engineering, since implanting large and thick engineered tissues can result in insufficient nutrition and oxygen transport to the inside of the implanted graft and this might result in graft rejection. To overcome this, much effort has been done in the field of engineering blood vessels, constructs containing a variety of blood vessel are widely studied, however, these constructs often are composed of unstable vessels, which are prone to degrade fast. In this study we used cyclic strain applied on endothelial cells and fibroblasts co-seeded on a gelfoam-stretchable-3D scaffold and examined the effect of the mechanical stimulation on the expansion, maturity and morphology of the newly forming vasculature. Moreover, we examined the role of YAP in sensing the mechanical stimulation and its effect on the forming vessels. Our results demonstrate that the mechanical stimulation prompt a more complex, developed and mature vascularization. Additionally, the cyclic strain resulted in an oriented structure of the forming vessels, this orientation was preserved upon implantation and enhanced the invading host vessel to orient in the same manner. This study shows the great potential of using cyclic strain in promoting the stabilization and organization of vessels within engineered tissues, which can be further utilized in the fabrication of large scaled clinically relevant engineered tissues.