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Review
. 2013 Apr 7;13(7):1201-12.
doi: 10.1039/c3lc41017j.

Microfabricated mammalian organ systems and their integration into models of whole animals and humans

Jong H Sung  1 , Mandy B Esch, Jean-Matthieu Prot, Christopher J Long, Alec Smith, James J Hickman, Michael L Shuler
Affiliations
Review

Microfabricated mammalian organ systems and their integration into models of whole animals and humans

Jong H Sung et al. Lab Chip. .

Abstract

While in vitro cell based systems have been an invaluable tool in biology, they often suffer from a lack of physiological relevance. The discrepancy between the in vitro and in vivo systems has been a bottleneck in drug development process and biological sciences. The recent progress in microtechnology has enabled manipulation of cellular environment at a physiologically relevant length scale, which has led to the development of novel in vitro organ systems, often termed 'organ-on-a-chip' systems. By mimicking the cellular environment of in vivo tissues, various organ-on-a-chip systems have been reported to reproduce target organ functions better than conventional in vitro model systems. Ultimately, these organ-on-a-chip systems will converge into multi-organ 'body-on-a-chip' systems composed of functional tissues that reproduce the dynamics of the whole-body response. Such microscale in vitro systems will open up new possibilities in medical science and in the pharmaceutical industry.

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Figures

Figure 1
Figure 1
Microfabricated organ systems mimicking various organ tissues. (A) Lung on a chip device modeling an alveolus and layout of fluid side of lung-based body-on-a-chip device fabricated in silicon. Reprinted from Long et al. with permission from Springer. (B) BBB on a chip, consisting of two perpendicular channels separated by a membrane. Reprinted with permission from Booth et al.. (C) The contractility of heart tissue is measure using the muscular thin film (MTF). Reprinted with permission from Grosberg et al.. (D) A microfluidic bioreactor for 3D liver tissue engineering. Reprinted with permission from Domansky et al40. (E) Microscale hydrogel scaffold mimicking the intestinal villi geometry. Reprinted with permission from Sung et al.. (F) Cantilever for detecting myotube contraction. Above: SEM micrograph of silicon cantilever array at 60x magnification. (scale bar = 5004m), Below: Confocal micrograph detailing top down view of a single cultured myotube on a cantilever. (scale bar = 204m). Reproduced with permission from Wilson et al.. (G) Microvascular network in 3D tissue scaffold made of collagen matrix. Reprinted with permission from Zheng et al..
Figure 2
Figure 2
Concept of physiologically-based pharmacokinetic (PBPK) model as a mathematical representation of the human body, and human-on-a-chip as a physical replication of a PBPK model.
Figure 3
Figure 3
(A) Schematics of 3-way connected culture, containing the hepatocytes, endothelial cells, adipose tissue. Reprinted with permission from Iori et al.. (B) Schematic of two sequentially perfused chambers (GI tract-liver). Reprinted with permission from van Midwoud et al.. (C) A multi-channel 3D microfluidic cell culture system (3D-μFCCS), containing four connected chambers on a chip. Reprinted with permission from Zhang et al.. (D) A microfluidic device for reproducing multi-organ interaction, containing three chambers connected with fluidic channels. Reprinted with permission from Sung et al..
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