Abstract

Engineering Printable 3D Vascularized Tissue Constructs

Shulamit Levenberg, Professor and Dean, Faculty of Biomedical Engineering, Technion Israel Institute of Technology

Living tissues require a vascular network to supply nutrients and gases and remove cellular waste. Fabricating vascularized constructs represents a key challenge in tissue engineering. Several methods have been proposed to create in vitro pre-vascularized tissues, including co-culturing of endothelial cells, support cells and cells specific to the tissue of interest. This approach supports formation of endothelial vessels and promotes endothelial and tissue-specific cell interactions. In addition, we have shown that in vitro pre-vascularization of engineered tissue can promote its survival and perfusion upon implantation.  Implanted vascular networks, can anastomose with host vasculature and form functional blood vessels in vivo. Sufficient vascularization in engineered tissues can be achieved through coordinated application of improved biomaterial systems with proper cell types. We have shown that vessel network maturity levels and morphology are highly regulated by matrix composition. We also explored the effect of mechanical forces on vessels organization and analyzed the vasculogenic dynamics within the constructs. We demonstrated that morphogenesis of 3D vascular networks is highly regulated by tensile forces.  Creating complex vascular networks with varying vessel sizes is the next challenge in engineering vascularized tissue constructs. 3D bioprinting, the controlled and automatized deposition of biomaterials and cells, represents a very attractive approach to solve this issue. This technique allows for combining different bioinks (biocompatible printable materials) in an organized fashion to attain native-tissue mimicking structures.