The Pivotal Role of Vascularization in Tissue Engineering

Abstract

Vascularization is one of the great challenges that tissue engineering faces in order to achieve sizeable tissue and organ substitutes that contain living cells. There are instances, such as skin replacement, in which a tissue-engineered substitute does not absolutely need a preexisting vascularization. However, tissue or organ substitutes in which any dimension, such as thickness, exceeds 400 μm need to be vascularized to ensure cellular survival. Consistent with the wide spectrum of approaches to tissue engineering itself, which vary from acellular synthetic biomaterials to purely biological living constructs, approaches to tissue-engineered vascularization cover numerous techniques. Those techniques range from micropatterns engineered in biomaterials to microvascular networks created by endothelial cells. In this review, we strive to provide a critical overview of the elements that must be considered in the pursuit of this goal and the major approaches that are investigated in hopes of achieving it.

Pre-cultivation of adipose tissue-derived microvascular fragments in porous scaffolds does not improve their in vivo vascularisation potential

“…Our finding that 90 % of all microvessels inside freshly seeded scaffolds stained positive for GFP indicates that this improved vascularisation was mainly caused by the reassembly of microvascular fragments into functional microvascular networks over time. This also resulted in higher tissue content inside the implants, further emphasising the importance of a sufficient vascularisation for the survival and successful incorporation of tissue constructs (Laschke et al, 2006;Auger et al, 2013).…”

“…The success of tissue engineering approaches depends on the establishment of an adequate vascularisation, which provides the basis for the onset of regenerative processes and guarantees the survival of cell-seeded implants (Laschke et al, 2006;Auger et al, 2013). Accordingly, various vascularisation strategies have been tested during the last years, ranging from the stimulation of angiogenesis at the defect site by sophisticated growth factor delivery systems to the generation of preformed microvascular networks inside tissue constructs prior to their implantation (Phelps and García, 2010;Novosel et al, 2011).…”

Transcriptional Profiling Reveals Crosstalk Between Mesenchymal Stem Cells and Endothelial Cells Promoting Prevascularization by Reciprocal Mechanisms

“…We first referred to two classic endothelial angiogenesis-related pathways both in vitro and in vivo: VEGF signaling [6,7,22] and angiopoietin/TIE2 signaling [34,35]. However, the RNA-seq results did not show significant elevation of upstream ligands or receptors for these pathways in co-HUVECs within 24 h. Alternatively, unbiased analysis demonstrated that a large proportion of experimentally validated NF-kB target genes (mainly based on www.bu.edu/NF-kB/gene-resources/target genes) were upregulated upon coculture for 12 and 24 h in both co-HUVECs and co-HMSCs (Fig.…”

“…Mesenchymal stem cells (MSCs), the stromal progenitor cells found in the bone marrow [3], were recently proved effective in vascular enhancement and protection [4,5]. Since tissue engineering is currently limited by the inability to adequately vascularize tissues surrounding the engineered constructs [6,7], the coimplantation of MSCs with human endothelial cells (ECs) recently succeed in creation of fully functional blood vessels under different circumstances in vivo [8][9][10], which could serve as a good solution for controlled vascularization. However, the cellular and molecular bases of MSCs-ECs interaction and their joint influence on endothelial vascularization were not fully understood.…”

In vitro pre-vascularization strategies for tissue engineered constructs–Bioprinting and others

“…As previously mentioned, the incorporation of a mature, inter-connected vascular network within a tissue construct is vital in tissue engineering as it helps to prevent the development of a necrotic core due to nutrient deficiency of cells deep within the construct, and provides a readily perfusable network for nutrient perfusion throughout the construct during the fabrication stage, or after implantation in a patient [15] . The implantation of a pre-vascularized tissue construct minimizes the need for vasculogenic and angiogenic processes to occur after implantation, and has been shown to induce rapid vascularization and inosculation with host vasculature upon implantation into mice when compared to un-vascularized constructs [16] .…”