Introduction of vasculature in engineered three-dimensional tissue.

Background: With recent developments in tissue engineering technology, various three-dimensional tissues can be generated now. However, as the tissue thickness increases due to three-dimensionalization, it is difficult to increase the tissue scale without introduction of blood vessels.

Main text: Many methods for vasculature induction have been reported recently. In this review, we introduced several methods which are adjustable vascularization in three-dimensional tissues according to three steps. First, "selection" provides potents for engineered tissues with vascularization ability. Second, "assembly technology" is used to fabricate tissues as three-dimensional structures and simultaneously inner neo-vasculature. Third, a "perfusion" technique is used for maturation of blood vessels in three-dimensional tissues. In "selection", selection of cells and materials gives the ability to promote angiogenesis in three-dimensional tissues. During the cell assembly step, cell sheet engineering, nanofilm coating technology, and three-dimensional printing technology could be used to produce vascularized three-dimensional tissues. Perfusion techniques to perfuse blood or cell culture medium throughout three-dimensional tissues with a unified inlet and outlet could induce functional blood vessels within retransplantable three-dimensional tissues. Combination of each step technology allows simulation of perivascular microenvironments in target tissues and drive vascularization in three-dimensional tissues.

Conclusion: The biomimetic microenvironment of target tissues will induce adequate cell-cell interaction, distance, cell morphology, and function within tissues. It could be accelerated for vascularization within three-dimensional tissues and give us the functional tissues. Since vascularized three-dimensional tissues are highly functional, they are expected to contribute to the development of regenerative medicine and drug safety tests for drug discovery in the future.