Microvasculature: An essential component for organ-on-chip systems
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Introduction The cost of drug development has increased dramatically during the last few decades due to the inefficiency of current preclinical drug evaluation models and the decreasing number of newly developed drugs.1 Major disadvantages of conventional preclinical models include a phylogenetic gap between human and animal models and a lack of similarity between two-dimensional (2D) cell culture systems and in vivo systems. Microengineering technologies combined with cell biology have been expected to solve this inefficiency by bridging the gap between human and preclinical models. The concept of “organs-on-chips” was proposed recently to establish in vitro models that precisely recreate in vivo characteristics as well as drug responses.2,3 Vascularization, a construction of the microvascular niche, is essential to mimic in vivo organ characteristics, as microvessels and capillaries cover organs almost entirely. In tissue engineering, vascularization has been emphasized to perfuse large-scale engineered tissue and supply oxygen and nutrients to interior cells, particularly for in vivo transplantation.4,5 In contrast, supplementation with oxygen and nutrients is not the main purpose of vascularization for organs-on-chips, as the entire system is typically small enough (a few hundred microns in dimension) to be supplied by oxygen diffusion in culture media. Instead, vascularization of organs-on-chips can establish in vivo-like target organ microenvironments, as microvascular endothelial
cells (ECs, a cell type that composes the interior surface of the blood vessels) play critical roles in organ function in cooperation with the cell types specific to each organ.6 In this review, we focus on the importance of vascularization for in vitro organ models. Beginning with the pathophysiological importance of the endothelium, subsequent sections will introduce specific features of chip-level in vitro microvascular mimicking systems. Recent efforts to vascularize organs-onchips and material considerations for establishing organs-onchips are also covered.
Organ-specific endothelial physiology The microvascular system is the infrastructure of the body that not only supplies oxygen and nutrients to tissues but is also related to numerous pathophysiological conditions. The microvascular endothelium, which is the internal surface of blood vessels consisting of ECs, plays diverse roles in organ function (Figure 1a). As the specific characteristics of each organ are determined by the endothelium,6,7 understanding endothelial organ specificity is necessary for reconstituting functional organs in vitro.
Selective barrier Although the selective barrier function is a natural and basic function of the endothelium, some organs have highly
Hyunjae Lee, Seoul National University; [email protected] Minhwan Chung, Seoul National University; [email protected] Noo Li Jeon, Seoul National University; [email protected] DOI: 10.1557/mrs.2013.286
© 2014 Materials Research Society
MRS BULLETIN • VOLUME 39 • JANUARY 2014 • www.mrs.org/bulletin
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