Cell-microenvironment interactions and architectures in microvascular systems

Abstract

In the past decade, significant advances have been made in the design and optimization of novel biomaterials and microfabrication techniques to generate vascularized tissues. Novel microfluidic systems have facilitated the development and optimization of in vitro models for exploring the complex pathophysiological phenomena that occur inside a microvascular environment. To date, most of these models have focused on engineering of increasingly complex systems, rather than analyzing the molecular and cellular mechanisms that drive microvascular network morphogenesis and remodeling. In fact, mutual interactions among endothelial cells (ECs), supporting mural cells and organ-specific cells, as well as between ECs and the extracellular matrix, are key driving forces for vascularization. This review focuses on the integration of materials science, microengineering and vascular biology for the development of in vitro microvascular systems. Various approaches currently being applied to study cell-cell/cell-matrix interactions, as well as biochemical/biophysical cues promoting vascularization and their impact on microvascular network formation, will be identified and discussed. Finally, this review will explore in vitro applications of microvascular systems, in vivo integration of transplanted vascularized tissues, and the important challenges for vascularization and controlling the microcirculatory system within the engineered tissues, especially for microfabrication approaches. It is likely that existing models and more complex models will further our understanding of the key elements of vascular network growth, stabilization and remodeling to translate basic research principles into functional, vascularized tissue constructs for regenerative medicine applications, drug screening and disease models.

Beyond organoids: In vitro vasculogenesis and angiogenesis using cells from mammals and zebrafish

“…Microfluidic systems give control over the biophysical and biochemical microenvironment of cells, allowing the analysis of complex interactions between different cell types and the respective signalling molecules [236].Microfluidic devices(chips) are made from various material (including glass and poly dimethyl-siloxane), using microfabrication techniques.…”

“…The devices can simply be connected to a medium reservoir to generate a passive flow through the channels; or to a pump for more constant flow rate ( Table 5). Using unique combinations of materials (with different structural and mechanical properties), microfabrication techniques, ECM components, growth factors, cell types and flow rates, a controlled environment can be created to promote vascular development [236].…”

Recapitulating the Vasculature Using Organ-On-Chip Technology

“…and can be switched on or off or be modified. This enables one to unravel the roles of these factors, individual or combined [2,16,[30][31][32][33][34][35]. However, it is important to ensure that the chosen method is best suited for the given research question while keeping the biological relevance in mind.…”

“…To assess this for Vasculature-on-Chip, we summarize the different approaches by dividing them into general categories based on the fabrication method used and discuss the different variations as well as possible applications (Figure 3). We illustrate the approaches with concrete examples that are typical for the methods discussed, but we are far from exhaustive in doing so [1,16,30,36,37].…”

Multicellular Vascularized Engineered Tissues through User‐Programmable Biomaterial Photodegradation

“…[13] Of note are recent efforts towards creating complex 3D networks using sacrificial lattices. In their seminal work, Miller et al encapsulated 3D-printed sugar glass in bioactive matrices, and then dissolved the lattice to reveal patterned interconnected channel networks.…”