Vascularization and Angiogenesis in Tissue Engineering: Beyond Creating Static Networks

Engineered tissues of a clinically relevant size need a vascular network to supply the cells with nutrients and oxygen. Including a vascular network before implantation can aid in this need, by connecting to the vasculature of the patient. To supply all cells with sufficient nutrients, and to successfully connect to the patient vasculature, the engineered vascular network needs to be highly organized. Using microfabrication technology such as photo patterning and bioprinting, the initial organization of vascular networks can be designed and controlled. The geometry of vascular networks can also be controlled by adapting local microenvironments. The patterning of mechanical signals, fluid flows, or the availability of growth factors leads to directed vascular organization. Engineered tissues need a vascular network to supply cells with nutrients and oxygen after implantation. A network that can connect to the vasculature of the patient after implantation can be included during in vitro culture. For optimal integration, this network needs to be highly organized, including venules, capillaries, and arterioles, to supply all of the cells with sufficient nutrients. Owing to the importance of vascularization for the clinical applicability of tissue engineering, many approaches have been investigated to include an organized vascular network in tissue constructs. This review will give an overview of recent efforts, and will propose future perspectives to engineer the optimal, functional vascular network. Engineered tissues need a vascular network to supply cells with nutrients and oxygen after implantation. A network that can connect to the vasculature of the patient after implantation can be included during in vitro culture. For optimal integration, this network needs to be highly organized, including venules, capillaries, and arterioles, to supply all of the cells with sufficient nutrients. Owing to the importance of vascularization for the clinical applicability of tissue engineering, many approaches have been investigated to include an organized vascular network in tissue constructs. This review will give an overview of recent efforts, and will propose future perspectives to engineer the optimal, functional vascular network. in the context of angiogenesis, the connection of two vascular structures. a precursor of endothelial cells, originating from the mesenchyme. a family of growth factors that mainly plays a role in vascular stabilization and destabilization. Generally, Angiopoietin 1 stabilizes vascular networks, while Angiopoietin 2 induces destabilization allowing for vascular remodeling. a finely distributed network of capillaries, which are the smallest of the blood vessels in the body, that takes care of the distribution of nutrients over a tissue. transmembrane receptors that play a role in cell–cell and cell–matrix interactions. The presence of specific integrins on a cell surface determines how a cell can respond to stimuli. a class of proteins that are part of the extracellular matrix and that influence cell adhesion, migration, and differentiation. cells, including vascular smooth muscle cells and pericytes, which are associated with vessels. Mural cells play a role in the stabilization of vascular structures. Apart from that, mural cells have contractile functionalities that can help to regulate the flow of fluid through vessels. a family of growth factors that play a role in cell growth and recruitment. In the context of angiogenesis, PDGF is mainly involved in the recruitment of mural cells. a sequence of peptides, Arg-Gly-Asp-Ser. Within fibronectin and several integrins, this is the sequence that mediates cell attachment. a protein that plays a role in the patterning of multiple systems during development. Shh is a morphogen and acts by the formation of concentration gradients, where cellular actions depend on the local concentration. a family of growth factors that play a role in angiogenesis and lymphangiogenesis. As one of the driving growth factors, VEGF is involved in many of the different angiogenic processes. a highly interconnected network of vascular structures, generally without a hierarchical organization. During embryonic development, a vascular plexus is first formed, which later remodels to a more organized network including arteries and veins.