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

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. Microphysiological systems have recently seen increasing reports of on‐chip microvascular network integration owing to the endothelium's critical role in natural physiology and tissue engineering. Herein, recent reports are reviewed, and five tunable ingredients are identified as independently and interdependently contributing to microvascular network formation via angiogenesis, vasculogenesis, and lymphangiogenesis.