Recent Advances on Cell-Based Co-Culture Strategies for Prevascularization in Tissue Engineering

Abstract

Currently, the fabrication of a functional vascular network to maintain the viability of engineered tissues is a major bottleneck in the way of developing a more advanced engineered construct. Inspired by vasculogenesis during the embryonic period, the in vitro prevascularization strategies have focused on optimizing communications and interactions of cells, biomaterial and culture conditions to develop a capillary-like network to tackle the aforementioned issue. Many of these studies employ a combination of endothelial lineage cells and supporting cells such as mesenchymal stem cells, fibroblasts, and perivascular cells to create a lumenized endothelial network. These supporting cells are necessary for the stabilization of the newly developed endothelial network. Moreover, to optimize endothelial network development without impairing biomechanical properties of scaffolds or differentiation of target tissue cells, several other factors, including target tissue, endothelial cell origins, the choice of supporting cell, culture condition, incorporated pro-angiogenic factors, and choice of biomaterial must be taken into account. The prevascularization method can also influence the endothelial lineage cell/supporting cell co-culture system to vascularize the bioengineered constructs. This review aims to investigate the recent advances on standard cells used in in vitro prevascularization methods, their co-culture systems, and conditions in which they form an organized and functional vascular network.

3D-Cultured Vascular-Like Networks Enable Validation of Vascular Disruption Properties of Drugs In Vitro

“…Profuse vascular 3D networks in vitro are established when culturing ECs in extracellular matrix mimicking gels such as collagen ( Koh et al, 2008 ), fibrin ( Nakatsu and Hughes, 2008 ), or synthetic hydrogels ( Liu et al, 2021 ) with additional proangiogenic supplements such as phorbol 12-myristate 13-acetate, sphingosine-1-phosphate, and/or angiogenic growth factors such as VEGF. Furthermore, the importance of organo-typic coculture conditions for successful in vitro prevascularization has been emphasized ( Shafiee et al, 2021 ). Coculturing ECs with other cells such as mesenchymal stem cells ( Uwamori et al, 2017 ) or human adipose stem cells (hASCs) ( Kang et al, 2018 ; Manikowski et al, 2018 ; Andrée et al, 2019 ) within a gel scaffold resulted in the generation of a 3D vascular network that was stable up to day 14.…”

Skin-on-a-Chip Technology: Microengineering Physiologically Relevant In Vitro Skin Models

“…One popular strategy to generate vascularization in skin grafts relies on the host vessels’ ability to invade the implanted engineered tissue [ 52 ]. Alternative approaches to induce vasculogenesis in vitro include cell seeding onto scaffolds or hydrogels, cell sheeting engineering and cell encapsulation [ 53 ]. However, most of these approaches involve complex and slow processes to induce vascularization, not suited for high-throughput applications.…”

In vitro dynamic perfusion of prevascularized OECs-DBMs (outgrowth endothelial progenitor cell - demineralized bone matrix) complex fused to recipient vessels in an internal inosculation manner

“…The basic concept of prevascularization technology is to pre-build a microvascular network on a tissue-engineered product before it is implanted into the body. Its advantage is that the tissue-engineered product does not have to wait for the recipient vessels to grow in slowly after implantation, but only needs the microvascular network on the scaffolds to inosculation with the recipient vessels [ 14 , 15 ], so that sufficient blood perfusion and nutritional support from the recipient area can be obtained within a short period of time. In vitro prevascularization can be achieved by growing endothelial cells (ECs) on a scaffold.…”

“…In vitro prevascularization can be achieved by growing endothelial cells (ECs) on a scaffold. ECs have the potential to spontaneously form blood vessels [ 14 , 16 ]. The difficulties are the availability of autologous vascular ECs and the limited in vitro amplification capacity.…”