New insights and advanced strategies for in vitro construction of vascularized tissue engineering.

Inadequate vascularization is a significant barrier to clinical application of large-volume tissue engineered grafts. In contrast to in vivo vascularization, in vitro prevascularization shortens the time required for host vessels to grow into the graft core and minimizes necrosis in the core region of the graft. However, the challenge of prevascularization is to construct hierarchical perfusable vascular networks, increase graft volume, and form a vascular tip that can anastomose with host vessels. Understanding advances in in vitro prevascularization techniques and new insights into angiogenesis could overcome these obstacles. In the present review, we discuss new perspectives on angiogenesis, the differences between in vivo and in vitro tissue vascularization, the four elements of prevascularized constructs, recent advances in perfusion-based in vitro prevascularized tissue fabrication, and prospects for large-volume prevascularized tissue engineering.