Abstract
Recent advances in integrating microengineering and tissue engineering have enabled the creation of promising microengineered physiological models, known as organ-on-a-chip (OOC), for experimental medicine and pharmaceutical research. OOCs have been used to recapitulate the physiologically critical features of specific human tissues and organs and their interactions. Application of chemical and mechanical stimuli is critical for tissue development and behavior, and they were also applied to OOC systems. Mechanical stimuli applied to tissues and organs are quite complex in vivo, which have not adequately recapitulated in OOCs. Due to the recent advancement of microengineering, more complicated and physiologically relevant mechanical stimuli are being introduced to OOC systems, and this is the right time to assess the published literature on this topic, especially focusing on the technical details of device design and equipment used. We first discuss the different types of mechanical stimuli applied to OOC systems: shear flow, compression, and stretch/strain. This is followed by the examples of mechanical stimuli-incorporated OOC systems. Finally, we discuss the potential OOC systems where various types of mechanical stimuli can be applied to a single OOC device, as a better, physiologically relevant recapitulation model, towards studying and evaluating experimental medicine, human disease modeling, drug development, and toxicology.
Highlights
Organ-on-a-chip (OOC) has enabled new opportunities in cell biology research through reproducing key aspects of an in vivo cellular microenvironment
Laminar flow used in this system generated the tangential shear stress on the human umbilical vein endothelial cells (HUVECs) and induced cell sprouting into the central channel
Mechanical stimuli found in the human body can be classified into (1) shear flow, (2) compression, and (3) stretch and strain [45], which have been demonstrated in OOC systems
Summary
Organ-on-a-chip (OOC) has enabled new opportunities in cell biology research through reproducing key aspects of an in vivo cellular microenvironment One of these parameters is mechanical force, which imparts strain on cells and tissues. Together with the presence of hormone and osmotic gradient, triggered the F-actin polymerization and depolymerization in both apical and basal regions of the cells, and the process is reversible These kidney-on-chip models can be used towards studying renal physiology and pathophysiology. Laminar flow used in this system generated the tangential shear stress on the HUVECs and induced cell sprouting into the central channel Another example was a liver-on-chip device, where the hepatocytes were 3D-cultured within a microfluidic channel to study drug toxicity in vitro [16]. Hepatotoxicity of the anti-inflammatory drug, diclofenac, was investigated using this liver-on-chip model to assess the short-term (
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