Endothelialization approaches for viable engineered tissues

One of the main limitation in obtaining thick, 3-dimensional viable engineered constructs is the inability to provide a sufficient and functional blood vessel system essential for the in vitro survival and the in vivo integration of the construct. Different strategies have been proposed to simulate the ingrowth of new blood vessels into engineered tissue, such as the use of growth factors, fabrication scaffold technologies, in vivo prevascularization and cell-based strategies, and it has been demonstrated that endothelial cells play a central role in the neovascularization process and in the control of blood vessel function. In particular, different "environmental" settings (origin, presence of supporting cells, biomaterial surface, presence of hemodynamic forces) strongly influence endothelial cell function, angiogenic potential and the in vivo formation of durable vessels. This review provides an overview of the different techniques developed so far for the vascularization of tissue-engineered constructs (with their advantages and pitfalls), focusing the attention on the recent development in the cell-based vascularization strategy and the in vivo applications.