Introduction of vasculature in engineered three-dimensional tissue

Sachiko Sekiya, Tatsuya Shimizu

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. 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. 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.