Engineering Vascularized Tissue Constructs
Prof. Shulamit Levenberg, Faculty of Biomedical Engineering, Technion, Haifa, Israel
Vascularization continues to represent a major challenge in the successful implementation of regenerative strategies. Cell organization into 3D tissue vascularized structures involves cell-matrix and cell-cell interactions, some of which occur between the different tissue cell types. During this process, cells further differentiate and assemble into structures resembling the final tissue architecture. We have established that vessel network assembly yielding vascularized 3D tissue structures can be induced in-vitro by means of coculturing endothelial cells, fibroblasts and tissue-specific cells. We have also shown that in vitro pre-vascularization of engineered tissues can promote tissue survival and further vascularization upon implantation, via anastomosis of the engineered vessels with host vasculature, forming functional blood vessels in vivo. Vascularization of engineered tissues can be enhanced through coordinated application of improved biomaterial systems with relevant cell types. Moreover, we have shown that vessel network maturity and morphology can be highly regulated by both matrix composition and by external mechanical stimulations. Our recent studies have focused on investigation of the degree of the in vitro prevascularization required to achieve best postimplantation vascularization of tissue constructs, as well as on understanding the mechanisms underlying host-implant vessel integration and anastomosis. New co-culture approaches for inducing pre-defined vessel structures in vitro will also be discussed, as will novel studies on vascularized muscle flaps engineered to reconstruct large soft tissue defects.