Table 3.
Various organ-on-a-chip systems for drug screening.
| Organ/tissue type | Drug model | Cell source | Chip material | ECM material | Fabrication technique | Readout signal | Application | Ref. |
|---|---|---|---|---|---|---|---|---|
| Heart | Verapamil | Primary neonatal CM | Quartz | Gelatin | Electron beam lithography | CM contraction status | Therapeutic efficacy evaluation | 109 |
| Gold | ||||||||
| Isoproterenol | Rat CM | PIPAAm | N/A | Laser engraver | Contractility | Therapeutic efficacy evaluation | 110 | |
| PDMS | ||||||||
| Doxorubicin | Human iPSC-CM | PDMS | Hydrogel | 3D bioprinting | Beating rate | Toxicity assessment | 111 | |
| PMMA | ||||||||
| Isoproterenol | Human iPSC-CM | PDMS | Gelatin | Soft lithography | Cardiac field potentials | Toxicity assessment | 112 | |
| Terfenadine | ||||||||
| Fexofenadine | ||||||||
| Liver | Acetaminophen | HepG2/C3A | PDMS | Fibronectin | N/A | Transcriptomics, proteomics and metabolomic profiles | Toxicity assessment | 123 |
| Acetaminophen | HepG2/C3A | PDMS | GelMA hydrogel | 3D bioprinting | Secretion rates of hepatocyte markers | Toxicity assessment | 113 | |
| PMMA | ||||||||
| Acetaminophen | Primary mouse hepatocytes | Silicon | N/A | Photolithography | Liver-related biomarkers | Toxicity assessment | 117 | |
| Chlorpromazine | PDMS | |||||||
| Tacrine | ||||||||
| Metformin | Primary human hepatocytes | PMMA | N/A | Laser cut | Cell viability | Therapeutic efficacy evaluation | 125 | |
| White adipocytes | PDMS | Insulin resistant biomarkers | ||||||
| Elafibranor | Human primary hepatocyte | Collagen | Hydrogel | Standard photolithography | Cell morphology | Therapeutic efficacy evaluation | 114 | |
| Kupffer cells | Hepatic biomarker level | |||||||
| Liver sinusoidal endothelial cells | ||||||||
| Hepatic stellate cells | ||||||||
| Hydrocortisone | Human primary hepatocytes | Commercialized LiverChip (CNBio Innovations) | N/A | N/A | Pharmacokinetic parameters | Metabolism study | 127 | |
| Kupffer cells | ||||||||
| Simvastatin | Primary rat hepatocytes | PDMS | Collagen | Photolithography | Cell viability | Metabolism study | 128 | |
| Atorvastatin | Human prostatic cancer cells | Glass | Soft lithography | Transcriptomics | ||||
| Metabolomics | ||||||||
| Kidney | Cyclosporine A | Proximal tubule epithelial cells | Silicon | Hydrogel | 3D bioprinting | Cell morphology | Toxicity assessment | 134 |
| Hydrogel | Cytoskeleton organization | |||||||
| Polymyxin B | Human primary proximal tubule epithelial cells | Nortis device | Collagen | N/A | Gene expression | Toxicity assessment | 135 | |
| Injury biomarkers | ||||||||
| Cholesterol concentrations | ||||||||
| Gentamicin | Madin–Darby canine kidney cells | PDMS | Fibronectin | UV polymerization | Cell viability | Toxicity assessment | 136 | |
| Kidney injury marker | ||||||||
| Cisplatin | Proximal tubule epithelial cells lines (ciPTEC-OAT1 and RPTEC) | OrganoPlate® | Collagen | N/A | Cell viability | Toxicity assessment | 137 | |
| Tenofovir | Biomarker release | |||||||
| Tobramycin | Barrier integrity | |||||||
| Cyclosporin A | Gene expression | |||||||
| Cisplatin | Renal proximal tubular epithelial cells | PDMS | Collagen | Laser-cutting | Cell viability | Toxicity assessment | 138 | |
| Gentamicin | Peritubular capillary endothelial cells | |||||||
| Cyclosporine A | ||||||||
| Adriamycin | Human iPSC-derived podocytes | PDMS | N/A | Stereolithography | Podocyte layer integrity | Toxicity assessment | 140 | |
| Human glomerular endothelial cells | Cell viability | |||||||
| Puromycin | Human podocytes | OrganoPlate™ | N/A | N/A | Podocyte morphology | Therapeutic efficacy evaluation | 141 | |
| Aminonucleoside | Glomerular endothelial cells | |||||||
| Brain | Dextrans 4 k, 20 k, 70 k | Endothelial cell line (b. End3) | PDMS | Fibronectin | Piranha etch | Cell viability | Drug delivery study | 142 |
| Propidium iodide | Astrocyte cell line (C8D1A) | Glass | Laser patterning | Astrocytic morphology | ||||
| Polycarbonate | TEER levels | |||||||
| Permeability | ||||||||
| Methamphetamine | Primary human brain microvascular endothelial cells | PDMS | Mixture of fibronectin and collagen | Soft lithograph | BBB permeability | Metabolism study | 143 | |
| Primary brain microvascular pericytes | PTE | Metabolites expression | ||||||
| Astrocytes | ||||||||
| Primary human neural cells | ||||||||
| Lung | Interleukin-13 | Primary human airway epithelial cells | PDMS | Collagen | Stereolithography | Gene expression | Therapeutic efficacy evaluation | 155 |
| Chemokines and cytokines concentrations | ||||||||
| Neutrophil adhesion | ||||||||
| Remdesivir | Human alveolar epithelial type II cell line | PDMS | Collagen | Conventional soft lithography | Alveolar-capillary barrier permeability | Therapeutic efficacy evaluation | 156 | |
| Lung microvasculature cell line | Inflammatory cytokines concentration | |||||||
| Gene expression | ||||||||
| Intestine | Ifosfamide | Human intestinal epithelial cells (Caco-2) | PDMS | Nitrocellulose | Soft photolithography | Drug metabolite level | Metabolism study | 158 |
| Verapamil | Collagen | |||||||
| Dimethyloxaloylglycine | Human intestinal epithelial cells (Caco-2) | PDMS | Collagen | Soft lithography | Intestinal permeability | Therapeutic efficacy evaluation | 159 | |
| Matrigel | ROS generation and lipid peroxidation | |||||||
| Injury-biomarker expression | ||||||||
| Nafamostat | Intestinal epithelium | Emulate™ | N/A | N/A | Viral load | Therapeutic efficacy evaluation | 160 | |
| Remdesivir | Cytokine secretion | |||||||
| Skin | Dexamethasone | Human keratinocyte cell line (HaCaTs) | PDMS | N/A | Soft lithography | Proinflammatory cytokine (IL-1β, IL-6) and chemokine (IL-8) levels | Therapeutic efficacy evaluation | 162 |
| HS27 Fibroblasts | ||||||||
| HUVEC | ||||||||
| Blood vessel | Sorafenib and sunitinib | HUVEC | PDMS | Collagen | 3D printing | Morphology of the angiogenic sprouts | Therapeutic efficacy evaluation | 166 |
| Liver/heart | Cyclophosphamide | Human iPSC-CM | PDMS | Collagen | Standard photolithography | Beat frequency | Metabolism-associated toxicity assessment | 176 |
| Terfenadine | Human primary hepatocytes | PMMA | Deep reactive ion etching | Conduction velocity | ||||
| HepG2/C3A | QT-interval | |||||||
| Contractile force | ||||||||
| Liver/kidney | Vitamin D3 | HepG2 | Device from ChipShop | N/A | N/A | Level of mRNA expression | Metabolism study | 177 |
| RPTEC | ||||||||
| HL60 cells | ||||||||
| Liver/muscle/neuron/heart | Doxorubicin | HepG2/C3A | Silicon on insulator (SOI) wafer | N/A | Photolithography | Cell viability | Toxicity assessment | 178 |
| Atorvastatin | iPSC-CM | Cell functionality | ||||||
| Valproic acid | Skeletal myofiber | |||||||
| Acetaminophen | Motoneurons | |||||||
| N-Acetyl-m-aminophenol | iPSC-neurons | |||||||
| Liver/heart/lung | Capecitabine | Primary human hepatocytes | Adhesive film | Hydrogel | Rapid-prototyping of patterned adhesive films | Cell viability | Metabolism-associated toxicity assessment | 179 |
| Ifosfamide | Hepatic stellate cells | Glass | ||||||
| Kupffer cells | PMMA | |||||||
| Liver-derived endothelial cells | ||||||||
| iPSC-CM | ||||||||
| Human cardiac fibroblast | ||||||||
| Cardiac endothelium cells | ||||||||
| A549 | ||||||||
| CC-2512 | ||||||||
| CC-2540 | ||||||||
| Lung/liver | Aflatoxin B1 | Human bronchial epithelial (NHBE) cells | Polyetheretherketone (PEEK) | Collagen | N/A | Cell viability | Metabolism-associated toxicity assessment | 180 |
| HepaRG™ cells | Transepithelial electrical resistance | |||||||
| Gene expression | ||||||||
| Liver/kidney | Aflatoxin B1 | HepG2 | Device from ChipShop | Collagen | N/A | Cell viability | Metabolism-associated toxicity assessment | 181 |
| Benzoalphapyrene | Hek293 | Cell survival curve | ||||||
| Intestines/kidney | Digoxin combined with colestyramine or verapamil | Caco-2 cells | PDMS | Collagen | Soft lithography | Cell apoptosis | Absorption-associated toxicity assessment | 183 |
| Primary rat glomerular microtissues | Micromolding | Cell viability | ||||||
| Lactate dehydrogenase leakage | ||||||||
| Gut/kidney | Ciprofloxacin | Caco-2 | Polycarbonate | N/A | Computer numerical control machining | Cell viability | Therapeutic efficacy | 184 |
| Gentamicin | HKC-8 | PDMS | Soft lithography | Transepithelial electrical resistance | Toxicity assessment | |||
| Glass | ||||||||
| Lung cancer | Doxorubicin | Lung cancer NCI–H1437 cells | Nusil medical grade silicone | Collagen | 3D printing | Impedance | Toxicity assessment | 192 |
| Docetaxel | Elastomer | pH | ||||||
| Glass | Cell viability | |||||||
| Breast cancer | Epirubicin | MDA-MB-231 | GelMA microdroplets | GelMA hydrogel | Electrohydrodynamic 3D printing | Cell viability | Toxicity assessment | 193 |
| Paclitaxel | Cell morphology | |||||||
| Heart/breast cancer | Doxorubicin | Human iPSC-CM | PDMS | Gelatin | Conventional photolithography | Cardiac biomarkers (Troponin T and CK-MB) | Chemotherapy-induced toxicity assessment | 197 |
| Fibroblasts | GelMA hydrogel | Breast cancer biomarker (HER-2) | ||||||
| Myofibroblasts | ||||||||
| SK-BR-3 | ||||||||
| Heart/colon cancer | Doxorubicin | iPSC-CM | PDMS | Fibrin gel | Soft lithography | Heart beating | Chemotherapy-induced toxicity assessment | 198 |
| Oxaliplatin | iPSC-EC | Replica molding | ||||||
| Colon adenocarcinoma cell line (SW620) | ||||||||
| Heart/liver cancer | Doxorubicin | Primary human CM | PDMS | Fibronectin | Multilayer soft lithography replica molding | Cell viability | Metabolism-associated toxicity assessment | 199 |
| HepG2 | Bovine gelatin | Release of lactate dehydrogenase (LDH) | ||||||
| Matrigel | ||||||||
| Liver/breast tumor | Capecitabine | HepG2 | PDMS | Alginate | Soft lithography | Cell viability | Metabolism-associated therapeutic efficacy evaluation | 200 |
| Irinotecan | HUVEC | PMMA | Agarose | |||||
| Adriamycin | HCT116 | Collagen | ||||||
| Epirubicin | MCF7 | Matrigel | ||||||
| Plumbagin | ||||||||
| Liver/colorectal cancer | Cyclophosphamide | Primary human hepatocytes | Polystyrene | N/A | Injection molding | Tumor microtissue diameters | Metabolism study | 201 |
| Ifosfamide | HCT116 | Toxicity assessment | ||||||
| Ritonavir | ||||||||
| Liver/bone marrow/uterine cancer | Mixture of doxorubicin, cyclosporine, and nicardipine | HepG2/C3A | Silicon, Plexiglass | Human blood plasma fibronectin | Photolithography | Cell viability | Therapeutic efficacy evaluation | 202 |
| MEG-01 | Deep reactive ion etching | |||||||
| MES-SA | ||||||||
| MES-SA/DX-5 | ||||||||
| Breast cancer/vascularized microenvironments | Adenosine | hBM-MSC | PDMS | Fibrin gel | Soft lithography | Cell viability | Therapeutic efficacy evaluation | 203 |
| OD hBM-MSC | Vessel permeability | |||||||
| GFP-HUVEC | Expression of antimetastatic marker A3AR | |||||||
| Cancer cell migration distance |
N/A, not applicable; CM, cardiomyocytes; ECM, extracellular matrix; BBB, blood–brain barrier; GelMA, gelatin methacryloyl; HUVEC, human umbilical vein endothelial cells; iPSC, induced pluripotent stem cells; PDMS, polydimethylsiloxane; PIPAAm, poly(N-isopropylacrylamide); PMMA, poly(methyl methacrylate); ROS, reactive oxygen species; TEER, transepithelial electrical resistance.