Vascularization Strategies for Tissue Engineering

Abstract

Tissue engineering is currently limited by the inability to adequately vascularize tissues in vitro or in vivo. Issues of nutrient perfusion and mass transport limitations, especially oxygen diffusion, restrict construct development to smaller than clinically relevant dimensions and limit the ability for in vivo integration. There is much interest in the field as researchers have undertaken a variety of approaches to vascularization, including material functionalization, scaffold design, microfabrication, bioreactor development, endothelial cell seeding, modular assembly, and in vivo systems. Efforts to model and measure oxygen diffusion and consumption within these engineered tissues have sought to quantitatively assess and improve these design strategies. This review assesses the current state of the field by outlining the prevailing approaches taken toward producing vascularized tissues and highlighting their strengths and weaknesses.

Study of the involvement of allogeneic MSCs in bone formation using the model of transgenic mice

“…Vascularization and mass transfer in grafts present some of the biggest challenges in the field of tissue engineering, because insufficient vascularization and limited diffusion of oxygen, nutrients and waste products can lead to necrosis within large reconstruction zones. 39,40 There have been 2 main approaches to solve this problem: 1) to implant a type of a repair element, in which the host cells and local microenvironment control in vivo vascularization, 2) to culture the cells under controlled conditions in vitro to develop a functioning vascular network before implantation. 41 Recently one more idea combining both approaches has been suggested.…”

“…It is based on the anastomosis between in vitro pre-engineered vessels and those of the host, so that the grafts do not have to rely solely on the host vessel invasion. 40,42 The mechanism, by which this anastomosis occurs between the pre-engineered vessels and the host vasculature, has recently been determined. The pre-engineered vessels surround the nearby host vessels and disrupt the underlying host endothelium, leading to the links between both networks.…”

“…These techniques include: introducing endothelial cells into the tissues via 3 D multicellular spheroids; simple mixing of different cultures such as fibroblasts, osteoblasts and endothelial cells; addition of angiogenic factors such as VEGF and bFGF. 40,44,45 MSCs may also be considered as a promising source for endothelial cells capable of vascular networks creation Bone marrow-derived MSCs predifferentiated by VEGF have been shown to acquire the phenotypic and functional features of endothelial cells and form characteristic capillary-like structures in vitro. 46,47 G.V.…”

Engineering Cardiovascular Regeneration

“…Studies on small rodent hearts did not reveal the severity of the problem we are facing by approaching therapy of the human heart which is more than two log units larger. If one linearly extrapolates the successful experiences in rats [102], a cardiac patch suitable for the repair of large MIs in humans needs to be several square centimeters in size and several millimeters in thickness, too big to be solely depending on diffusion [112]. So either we expect the patch to sufficiently grow in size by cellular proliferation or we need pre-vascularization.…”

Bioengineering of Colo-Rectal Tissue

“…Currently, construct development is often restricted to smaller than clinically relevant size due to issues of (in-)sufficient oxygen and nutrient supply. Consequently, feasibility of in vivo integration of the bioengineered tissue may be constrained (Lovett et al, 2009). Interposition of bioengineered substitutes organized in a tubular fashion, such as the gut, appear to be particularly prone to complications (Badylak, S. et al, 2000;Chen & Badylak, 2001;Thompson et al, 1986).…”