Formation of Stable Vascular Networks in Engineered Tissues

Abstract

Proper vascular network structure is essential for normal tissue function. The vasculature provides oxygen, nutrients and immune cells, as well as removes tissue waste and byproducts. (Jain 2003) In tissue engineering and regenerative medicine, the existence of functional blood vessels is critical to the survival of the newly generated tissue. Current strategies for promoting new blood vessel formation, or neovascularization, have mostly focused on angiogenesis, which is the formation of new capillaries from pre-existing vessels by sprouting of endothelial cells (ECs). (Carmeliet 2003) Another mechanism of neovascularization, vasculogenesis, which is the in situ assembly of endothelial progenitors into capillaries, has also been explored as a method for stimulating new vessel formation. Genes or proteins of angiogenic factors have been delivered systematically or directly to a target tissue to promote neovascularization via either angiogenesis or vasculogenesis. For example, proteins from the vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) families delivered by various methods have been investigated extensively for enhancing neovascularization. (Brey et al., 2005; Brey & McIntire, 2008) While the delivery of angiogenic factors has been successful in promoting new capillary formation, the structure of the newly formed vessels is often non-ideal. The vessels can be immature, with small diameters and lack of some essential cellular and extracellular components required for proper function. Immature vascular structure may result in poor blood perfusion and possibly vessel regression upon a decrease in the vascular stimulus. (Benjamin et al., 1999) In addition, the formation of small capillaries alone is not likely to be sufficient for vascularization of large, complex tissues, which are often needed for tissue engineering. Therefore, the goal of neovascularization in engineered tissue should be focused not only on the initial assembly of capillaries via angiogenesis or vasculogenesis, but also the expansion and stabilization of new vessels, which means the formation of mature, long-lasting vessels with dimensions that meet the requirement of high conductance blood flow. (Carmeliet & Conway, 2001) In this chapter, we will discuss current status in the generation of stable, long-lasting vascular networks in tissue engineering and regenerative medicine, identifying recent advances and limitations yet to be overcome.