Abstract
Tissue chips (TCs) and microphysiological systems (MPSs) that incorporate human cells are novel platforms to model disease and screen drugs and provide an alternative to traditional animal studies. This review highlights the basic definitions of TCs and MPSs, examines four major organs/tissues, identifies critical parameters for organization and function (tissue organization, blood flow, and physical stresses), reviews current microfluidic approaches to recreate tissues, and discusses current shortcomings and future directions for the development and application of these technologies. The organs emphasized are those involved in the metabolism or excretion of drugs (hepatic and renal systems) and organs sensitive to drug toxicity (cardiovascular system). This article examines the microfluidic/microfabrication approaches for each organ individually and identifies specific examples of TCs. This review will provide an excellent starting point for understanding, designing, and constructing novel TCs for possible integration within MPS.
Highlights
The heart can be considered as two pumps that work in synchrony, with the right side of the heart involved in pumping deoxygenated blood from the systemic circulation into the lungs for oxygenation and release of carbon dioxide, and the left side of the heart receiving that oxygen-rich blood and pumping it forward to the rest of the body
The liver parenchyma is composed of specialized epithelial cells called hepatocytes (HCs), and the stroma consists of hepatic stellate cells (HSCs), which are specialized mesenchymal cells, resident macrophages called Kupffer cells (KCs), fenestrated liver sinusoid endothelial cells (LSECs), and a small number of cholangiocytes, which line the bile ducts
The renal corpuscle consists of four different cell types, including the glomerular endothelial cells (GECs) and mesangial cells (MCs) found within the glomerulus, the podocytes of the visceral Bowman’s capsule layer, and the parietal epithelial cells (PEpCs) of the parietal Bowman’s capsule layer
Summary
“Tissue chips” can be defined as “engineered in vitro devices that can be used to model both structure and function of working units in the body, including organs such as the brain, heart, lungs, liver, gut, pancreas, and kidneys and tissues such as skeletal muscle, adipose tissue, and bone.” Such models utilize cells (preferably of human origin, to avoid interspecies differences), extracellular matrix (ECM), and biomaterials to fabricate 3D multicellular constructs in environments where cellular interactions (cell–cell, cell–ECM), biomechanical stresses (shear, pressure, stretch), bioelectrical signals, and soluble factor signaling (certain hormones, growth factors, cytokines) are all replicated to accurately model in vivo-like responses. Microfabrication techniques and play an essential volved in metabolizing or excreting drugs (liver andmicrofluidic kidney) or aretechnologies frequently damaged role in the construction and operation of TCs and MPSs. Each tissue type requires efficient design consideration to enable proper functionality. The following review articles provide comprehensive overviews of TCs and their use in drug testing [11,12] and disease modeling [13]
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