Table 2.

Representative microphysiological systems

Organs	Design considerations			Fabrication/Biomaterials	Applications	Refs
	Anatomy	Physiology	Cells
Micro-vasculature	endothelial layer of BBB	fluidic shear stress	HUVECs, hCMEC/D3	Microfluidics	drug testing	160, 161
	co-culture of BBB	fluidic shear stress	endothelial cell line/astrocytic cell line	microfluidics	drug testing	162
			hBMVEC/pericytes/astrocytes		drug testing	100
	blood vessel	fluidic shear stress	HUVECs/mouse fibroblasts/mouse smooth muscle cells	microextrusion bioprinting, microfluidics	system development*	91
Brain	multi-layered neural tissue	–	rat embryonic neurons and astrocytes, mouse neural stem cells, mouse primary cortical neurons	microextrusion bioprinting	system development	163–165
	brain	–	hESCs, hPSCs	microwell array lading	system development	105, 166–168
		fluidic shear stress	hESCs	microfluidics, microwell array lading	drug testing	169
Eye	corneal epithelial layer	–	human limbal cells	human amniotic membrane	epithelium transplantation	34
	corneal stroma	cell alignment	human and rabbit corneal fibroblasts, hCSSCs/hCFs	silk microgrooves	system development	41, 170
		–	human keratocytes	microextrusion bioprinting	system development	42
	corneal endothelial layer	mechanical properties	primary human corneal endothelial cells, human, sheep or bovine corneal endothelial cell lines	hydrogel substrates	system development	36, 171–173
	3-D corneal tissue	cell alignment	human corneal epithelial cells/hCSSCs/ chicken DRG	nanogratings	system development	44
	full-thickness cornea	–	rabbit corneal epithelial cells/keratocytes/endothelial cells	fibrin-agarose hydrogels	system development	43
			hESC-derived limbal epithelial cell-like cells/corneal endothelial cell-like cells	decellularized porcine cornea	cornea transplantation	174
	3-D retina	–	retinal progenitor cells cell line/RPE	–	system development	85
	ocular surface	blink-induced mechanical forces	primary human corneal epithelial cells, immortalized human conjunctival epithelial cells and primary human keratocytes	microfluidics	drug testing	8
Heart	aligned myocardium	–	hPSC-derived cardiomyocytes	–	system development	175
		fluidic shear stress	rat cardiac myocytes	microfluidics	drug testing	101
		mechanical properties, fluidic shear stress	embryonic cardiomyoblast line	microfluidics	system development	176
	laminar cardiac tissue	fluidic shear stress	hiPSC-derived cardiomyocytes	microfluidics	drug testing	177
	heart components	mechanical properties	hESC derived cardiomyocytes	microextrusion bioprinting	system development	116
Lung	alveolar epithelial layer	mechanical stretch	human bronchial epithelial cells	–	drug testing	178
	alveolar-capillary interface	mechanical stretch	human alveolar epithelial cells, airway epithelial cells/microvascular endothelial cells	microfluidics	nanotoxicity study, lung disease modeling	4, 16, 64
	alveolar respiratory membrane	–	non-small cell lung cancer cells/human fetal lung fibroblasts/HUVECs	microfluidics, electrospinning	drug testing	96
Liver	hepatocyte aggregate	fluidic shear stress	rat hepatocytes	microfluidics	drug testing	179
			human hepatocyte line	inkjet bioprinting, microwell array lading, microfluidics	drug testing	87
	hepatic sinusoid	fluidic shear stress	human hepatocyte line	microwell array lading, microfluidics	system development	180
		fluidic shear stress	mouse hepatocytes	microfluidics	drug testing	97
Kidney	nephron	–	hiPSCs, hESCs	microwell array lading	drug testing	88
	proximal tubule	fluidic shear stress	human proximal tubule epithelial cells	microextrusion bioprinting, microfluidics	drug testing	92
			human kidney proximal tubular epithelial cells, canine kidney cells	microfluidics	drug testing	98
			human proximal tubule epithelial cells	microfluidics	system development	181
Gut	intestinal villi	–	human epithelial colorectal adenocarcinoma cells, human epithelial cell line	alginate micropits	system development	182
	intestinal epithelium	fluidic shear stress, mechanical stretch	hiPSCs	microwell array lading, microfluidics	drug testing	89
		fluidic shear stress	human epithelial cells	microfluidics	system development	99, 183, 184
	intestinal epithelial organoids	–	hiPSCs	microwell array lading	system development	185
Tumor	tumor-vascular interface	fluidic shear stress	HDMECs/ human breast cancer cells	microfluidics	system development	186
			HUVECs, human lung fibroblasts, monocytes, human breast cancer cell line, human melanoma cancer cell line	microfluidics	system development	187
	tumor-stromal interaction	fluidic shear stress	bone marrow stromal cells/liver tumor cell line	microfluidics	system development	188
	compartmentalized structure of glioblastima	oxygen gradient	patient-derived glioblastoma cells and vascular endothelial cells	microextrusion bioprinting	drug testingdrug testing	95

Notes:

^*system development: no application reported

HUVEC: human umbilical vein endothelial cells; hCMEC/D3: human cerebral microvessel endothelial cells; hBMVEC: human brain-derived microvascular endothelial cells; hCSSCs: human corneal stromal stem cells; hCFs: human corneal fibroblasts; DRG: dorsal root ganglion; hESCs: human embryonic stem cells; RPE: retinal pigment epithelium; hPSCs: human pluripotent stem cells; hiPSCs: human induced pluripotent stem cells; MSCs: human mesenchymal stromal cells; HDMECs: human dermal microvascular cells