Engineering New Microvascular Networks On‐Chip: Ingredients, Assembly, and Best Practices

Abstract

Tissue engineered grafts show great potential as regenerative implants for diseased or injured tissues within the human body. However, these grafts suffer from poor nutrient perfusion and waste transport, thus decreasing their viability post-transplantation. Graft vascularization is therefore a major area of focus within tissue engineering because biologically relevant conduits for nutrient and oxygen perfusion can improve viability post-implantation. Many researchers used microphysiological systems as testing platforms for potential grafts owing to an ability to integrate vascular networks as well as biological characteristics such as fluid perfusion, 3D architecture, compartmentalization of tissue-specific materials, and biophysical and biochemical cues. Although many methods of vascularizing these systems exist, microvascular self-assembly has great potential for bench-to-clinic translation as it relies on naturally occurring physiological events. In this review, the past decade of literature is highlighted, and the most important and tunable components yielding a self-assembled vascular network on chip are critically discussed: endothelial cell source, tissue-specific supporting cells, biomaterial scaffolds, biochemical cues, and biophysical forces. This paper discusses the bioengineered systems of angiogenesis, vasculogenesis, and lymphangiogenesis and includes a brief overview of multicellular systems. It concludes with future avenues of research to guide the next generation of vascularized microfluidic models.

Microfluidic Tissue Engineering and Bio‐Actuation

“…The vascularization studies carried out on microfluidic devices culminated in the engineering of networks of perfusable cellular microvessels, [260] which were realized by precisely controlling the vascular microenvironment cues in vitro. [295][296][297] In certain models, the survival of the surrounding tissue entirely depends on the nutrients supplied by these vessels. In 2016, Sobrino et al generated vascularized 3D microtumors in an "on-a-chip" platform.…”

In Vitro, In Vivo, and In Silico Models of Lymphangiogenesis in Solid Malignancies

“…However, it is important to incorporate more biological components of the microenvironment to advance the understanding of tissue interactions in normal but also in pathological conditions. More information about the best practices for engineering new microvascular networks on-chip in the context of LA can be found in the paper of Tronolone and Jain [83].…”

Engineered 3D vessel-on-chip using hiPSC-derived endothelial- and vascular smooth muscle cells

“…Nevertheless, and despite recent advances, many current in vitro models of blood vessels fail to emulate the integrated, complex and multicell-type composition of the human vasculature and do not include a mimic of blood flow ( Duval et al., 2017 ). To address this, microfluidic devices have been engineered that do incorporate these features and provide the environment for the formation of multi-cell type 3D tissues and vessels-on-chip (VoC) ( Tronolone and Jain, 2021 ). Typically, cells incorporated in these microphysiological devices are derived from non-human sources, human (tumor) cell lines, or directly from primary human tissue.…”

“…Typically, cells incorporated in these microphysiological devices are derived from non-human sources, human (tumor) cell lines, or directly from primary human tissue. Primary human cells provide the closest mimic to human blood vessels but are of limited availability and of variable genetic origin ( Tronolone and Jain, 2021 ). While hiPSC derivatives are now regarded as an alternative, they have so far largely been used in combination with primary cells in microfluidic chips.…”