Systems for therapeutic angiogenesis in tissue engineering

The goals in tissue engineering include the replacement of damaged, injured , or missing body tissues with biologically compatible substitutes. To over come initial tissue-mass loss, improved vascularization of the regenerated tissue is essential. Two pathways of tissue neovascularization are known: v asculogenesis, the in situ assembly of capillaries from undifferentiated en dothelial cells (EC), and angiogenesis, the sprouting of capillaries from p reexisting blood vessels. Recent advances in our understanding of the proce ss of blood-vessel growth have provided significant tools for the neovascul arization of bioengineered tissues. Several growth factors serve as stimuli for EC proliferation and migration as well as the formation of new blood v essels. They convey their effects via specific receptors expressed on the s urface of EC. Vascular epithelial growth factor (VEGF) is a major regulator of neovascularization. VEGF plays a major role in the early development of blood-cell progenitors. Basic fibroblast growth factor (bFGF) was identifi ed as the first angiogenic factor. It is a potent inducer of EC proliferati on and blood-vessel growth in vitro and in vivo. VEGF and bFGF have been in jected into undervascularized ischemic tissues, resulting in new blood-vess el formation and tissue perfusion. Gene-therapy approaches using VEGF cDNA injection into ischemic tissues have augmented the formation of collateral vessels. Angiogenic factors such as VEGF and bFGF have also been incorporat ed into bioengineered tissues and have facilitated blood-vessel growth. Oth er approaches such as prevascularization of the matrix prior to cell seedin g and incorporation of EC into the bioengineered tissues have produced enco uraging results. This article reviews the process of blood-vessel growth an d tissue vascularization, placing emphasis on strategies that can be employ ed for efficient vascularization of engineered tissues in vitro and in vivo .