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.

Improved vascular organization enhances functional integration of engineered skeletal muscle grafts

“…Tissue survival is dependent on oxygen supply, which is limited to a diffusion distance of up to 300 μm from a supplying blood vessel (7,8). Therefore, long-term survival and function is depending on rapid vascularization, which provides for the metabolic needs of the tissue.…”

Prediction of spatio-temporal bone formation in scaffold by diffusion equation

“…All animals were scanned at 7 time points (2,4,7,11,15,22 and 35 weeks after surgery) using SkyScan 1076 In Vivo Scanner (SkyScan, Belgium). Each leg was stretched and separated from the body and scanned along with two phantoms and a tube of water for calibration purposes.…”

“…It involves migration of several cell types [1], proliferation [2], differentiation [3], angiogenesis [4,5], and mineralization [6], as well as the interaction of numerous cytokines and growth factors [7]. Bone formation also depends on the architecture of the scaffold [8], its surface properties [9], the mechanical stimulation [10,11], the implantation site [12], and the boneescaffold interface [13].…”

Cell colonization in degradable 3D porous matrices

“…7 Bioregulation of the porous matrix can also be achieved by the incorporation of growth factors. For example growth factors such as vascular endothelial growth factor (VEGF) 116 and basic fibroblast growth factor (bFGF) 118,119 as well as ECM components such as fibronectin 120 are important in angiogenesis. Growth factors are typically proteins with short half-lives.…”