Angiogenesis in Tissue Engineering: Breathing Life into Constructed Tissue Substitutes

Abstract

Long-term function of three-dimensional (3D) tissue constructs depends on adequate vascularization after implantation. Accordingly, research in tissue engineering has focused on the analysis of angiogenesis. For this purpose, 2 sophisticated in vivo models (the chorioallantoic membrane and the dorsal skinfold chamber) have recently been introduced in tissue engineering research, allowing a more detailed analysis of angiogenic dysfunction and engraftment failure. To achieve vascularization of tissue constructs, several approaches are currently under investigation. These include the modification of biomaterial properties of scaffolds and the stimulation of blood vessel development and maturation by different growth factors using slow-release devices through pre-encapsulated microspheres. Moreover, new microvascular networks in tissue substitutes can be engineered by using endothelial cells and stem cells or by creating arteriovenous shunt loops. Nonetheless, the currently used techniques are not sufficient to induce the rapid vascularization necessary for an adequate cellular oxygen supply. Thus, future directions of research should focus on the creation of microvascular networks within 3D tissue constructs in vitro before implantation or by co-stimulation of angiogenesis and parenchymal cell proliferation to engineer the vascularized tissue substitute in situ.

Porous microspheres support mesenchymal progenitor cell ingrowth and stimulate angiogenesis

“…This could stimulate the endogenous release of angiogenic growth factors from the hypoxic cells. 55 It is also possible that the microspheres provide physical protection to cells, which would keep cells in a concentrated area instead of dispersing in the CAM. Early differentiation (days 4-14) of MSC cells into osteoblasts is typically marked by an upregulation of vascular endothelial growth factor (VEGF) from the cells.…”

Controlling Stem Cell Fate with Material Design

“…In tissue engineering applications, it is necessary to not only stimulate the differentiation of stem cells into the specialized tissue cell of interest, but to also allow for formation of vasculature in the tissue. [91] Two growth factors intimately involved in the process of vascularization are vascular endothelial growth factor (VEGF) and PDGF. However, it is not only the presence of these two factors that influences angiogenesis, but also their temporal presentation.…”

Design concepts and strategies for tissue engineering scaffolds

“…However, there remain a number of challenges, including the inhomogeneous distribution of cells within the construct after seeding. Also, the seeding of endothelial cells does not necessarily result in the development of new blood vessels in vitro because the process depends on the coordinated release of various signaling factors and involves other cell types, including smooth muscle cells and pericytes, which are normally found in vivo but not necessarily in vitro [170]. Another novel approach is to incorporate oxygengenerating particles into the scaffold construct to prolong cell survival until host tissue neovascularization is achieved.…”