Systems for therapeutic angiogenesis in tissue engineering

Abstract

The goals in tissue engineering include the replacement of damaged, injured, or missing body tissues with biologically compatible substitutes. To overcome initial tissue-mass loss, improved vascularization of the regenerated tissue is essential. Two pathways of tissue neovascularization are known: vasculogenesis, the in situ assembly of capillaries from undifferentiated endothelial cells (EC), and angiogenesis, the sprouting of capillaries from preexisting blood vessels. Recent advances in our understanding of the process of bloodvessel growth have provided significant tools for the neovascularization of bioengineered tissues. Several growth factors serve as stimuli for EC proliferation and migration as well as the formation of new blood vessels. They convey their effects via specific receptors expressed on the surface 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 identified as the first angiogenic factor. It is a potent inducer of EC proliferation and blood-vessel growth in vitro and in vivo. VEGF and bFGF have been injected into undervascularized ischemic tissues, resulting in new blood-vessel 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 incorporated into bioengineered tissues and have facilitated blood-vessel growth. Other approaches such as prevascularization of the matrix prior to cell seeding and incorporation of EC into the bioengineered tissues have produced encouraging results. This article reviews the process of blood-vessel growth and tissue vascularization, placing emphasis on strategies that can be employed for efficient vascularization of engineered tissues in vitro and in vivo.

Neovascularization of poly(ether ester) block‐copolymer scaffolds in vivo: Long‐term investigations using intravital fluorescent microscopy

“…[27][28][29] Data on neovascularization of biomaterials are based today mainly on semiquantitative histological studies. 10,19,29,30 The dynamic temporal course of neovascularization was previously evaluated by means of magnetic resonance imaging techniques in animals 31 as well as in humans.…”

Design of Nano- and Microfiber Combined Scaffolds by Electrospinning of Collagen onto Starch-Based Fiber Meshes: A Man-Made Equivalent of Natural Extracellular Matrix

“…23 To create a vascularized scaffold, a number of methods have been proposed. 24,25 One approach involves the transplantation of ECs in an effort to engineer a vascular network from these cells, rather than waiting for host-blood-vessel ingrowth. 26 However, independently of the adopted approach to accelerate vascularization, all of them will involve directly or indirectly ECs.…”

STAT3-Dependent Mouse Embryonic Stem Cell Differentiation Into Cardiomyocytes

“…1 Tissue engineering by stem cell therapy for the replacement of lost or damaged tissue with biologically compatible substitutes is a promising therapy for cardiac repair. 2 Recent evidence in animal models has shown that both embryonic and adult-derived stem cells have the capacity to differentiate into cardiovascular cell types including cardiomyocytes (CMC) and to improve cardiac function when transplanted after cardiac injury. 3,4 These findings lead to several ongoing human clinical trials.…”