ABSTRACT
Tissues The main factors responsible for introducing blood vessel networks within engineered tissues are the cell sources composing the vessel wall and growth factors stimulating cell growth and migration, which lead to network formation. In addition, continuous tubular formation of the vessel structure is essential for perfusion of blood or culture media. A simple strategy for neovascularization in 3D tissues
is to wait for host-originated blood vessel formation (Fig. 6c.1). In the early days of tissue engineering, most researchers expected the host to use its own regeneration power. Relying on the host vascularization potential is sufficient for fabrication of thin tissues, including skin epithelium and cell-sparse tissues such as bone and cartilage. However, primary ischemia prior to sufficient host-originated neovascularization has limited the viability of engineered tissue in cell-dense and thicker tissues, including the heart, liver, and kidney. Therefore accelerating blood vessel formation with growth factors has been pursued as one of the strategies for vascularization in 3D tissues (Fig. 6c.2). Endothelial cell coculture within engineered tissues is another strategy that prepares the blood vessel component in advance and enhances microcapillary formation within the tissues, often being combined with growth factors (Fig. 6c.3). Functional blood vessel formation in engineered tissues has now been successfully achieved in vivo because blood-perfusable tubular structures form naturally and simultaneously as endothelial cells form a network. However in vitro perfusable blood vessel formation still presents a major hurdle. In vitro induction of continuous endothelial cell tubular structures is now the key technology that needs to be established. Previously reported technologies for neovascularization in bioengineered 3D tissues are described below.
