Organs-on-a-chip: a union of tissue engineering and microfabrication

• Thomson G.W.

Quinidine as a cause of sudden death.

Circulation. 1956; 14: 757-765

• Jeon J.S.
• et al.

Generation of 3D functional microvascular networks with human mesenchymal stem cells in microfluidic systems.

Integr. Biol. (Camb.). 2014; 6: 555-563

• Phan D.T.T.
• et al.

A vascularized and perfused organ-on-a-chip platform for large-scale drug screening applications.

Lab Chip. 2017; 17: 511-520

• Prodanov L.
• et al.

Long-term maintenance of a microfluidic 3D human liver sinusoid.

Biotechnol. Bioeng. 2016; 113: 241-246

• Ma L.D.
• et al.

Design and fabrication of a liver-on-a-chip platform for convenient, highly efficient, and safe in situ perfusion culture of 3D hepatic spheroids.

Lab Chip. 2018; 18: 2547-2562

• Zhao Y.
• et al.

Rapid wire casting: a multimaterial microphysiological platform enabled by rapid casting of elastic microwires.

Adv. Healthc. Mater. 2019; 81970019

• Lind J.U.
• et al.

Instrumented cardiac microphysiological devices via multimaterial three-dimensional printing.

Nat. Mater. 2017; 16: 303-308

• Jalili-Firoozinezhad S.
• et al.

A complex human gut microbiome cultured in an anaerobic intestine-on-a-chip.

Nat. Biomed. Eng. 2019; 3: 520-531

• Musah S.
• et al.

Mature induced-pluripotent-stem-cell-derived human podocytes reconstitute kidney glomerular-capillary-wall function on a chip.

Nat. Biomed. Eng. 2017; 1: 0069

• Booth R.
• Kim H.

Characterization of a microfluidic in vitro model of the blood-brain barrier (muBBB).

Lab Chip. 2012; 12: 1784-1792

• Lee J.H.
• et al.

Microfluidic 3D bone tissue model for high-throughput evaluation of wound-healing and infection-preventing biomaterials.

Biomaterials. 2012; 33: 999-1006

• Rafatian N.
• et al.

Drawing inspiration from developmental biology for cardiac tissue engineers.

Adv. Biol. (Weinh.). 2021; 5e2000190

• Duffy D.C.
• et al.

Rapid prototyping of microfluidic systems in poly(dimethylsiloxane).

Anal. Chem. 1998; 70: 4974-4984

• Sin A.
• et al.

The design and fabrication of three-chamber microscale cell culture analog devices with integrated dissolved oxygen sensors.

Biotechnol. Prog. 2004; 20: 338-345

• Huh D.
• et al.

Reconstituting organ-level lung functions on a chip.

Science. 2010; 328: 1662-1668

• Riaz M.
• et al.

Muscle LIM protein force-sensing mediates sarcomeric biomechanical signaling in human familial hypertrophic cardiomyopathy.

Circulation. 2022; 145: 1238-1253

• Zhao Y.
• et al.

A platform for generation of chamber-specific cardiac tissues and disease modeling.

Cell. 2019; 176: 913-927

• Brown B.N.
• Badylak S.F.

Extracellular matrix as an inductive scaffold for functional tissue reconstruction.

Transl. Res. 2014; 163: 268-285

• Swinehart I.T.
• Badylak S.F.

Extracellular matrix bioscaffolds in tissue remodeling and morphogenesis.

Dev. Dyn. 2016; 245: 351-360

• Zhao Y.
• et al.

Engineering microenvironment for human cardiac tissue assembly in heart-on-a-chip platform.

Matrix Biol. 2020; 85–86: 189-204

• Wufuer M.
• et al.

Skin-on-a-chip model simulating inflammation, edema and drug-based treatment.

Sci. Rep. 2016; 6: 37471

• Kasendra M.
• et al.

Development of a primary human small intestine-on-a-chip using biopsy-derived organoids.

Sci. Rep. 2018; 8: 2871

• Takahashi K.
• Yamanaka S.

Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.

Cell. 2006; 126: 663-676

• Takahashi K.
• et al.

Induction of pluripotent stem cells from adult human fibroblasts by defined factors.

Cell. 2007; 131: 861-872

• Hinson J.T.
• et al.

Heart disease. Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy.

Science. 2015; 349: 982-986

• Wang G.
• et al.

Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies.

Nat. Med. 2014; 20: 616-623

• Bergmann O.
• et al.

Evidence for cardiomyocyte renewal in humans.

Science. 2009; 324: 98-102

• Zhao Y.
• et al.

Towards chamber specific heart-on-a-chip for drug testing applications.

Adv. Drug Deliv. Rev. 2020; 165-166: 60-76

• Ronaldson-Bouchard K.
• et al.

Advanced maturation of human cardiac tissue grown from pluripotent stem cells.

Nature. 2018; 556: 239-243

• Lundy S.D.
• et al.

Structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells.

Stem Cells Dev. 2013; 22: 1991-2002

• Callaghan N.I.
• et al.

Advanced physiological maturation of iPSC-derived human cardiomyocytes using an algorithm-directed optimization of defined media components.

bioRxiv. 2022; ()

• Dhahri W.
• et al.

Abstract 291: In vitro matured human embryonic stem cell-derived cardiomyocytes form grafts with enhanced structure and improved electromechanical integration in injured hearts.

Circ. Res. 2020; 127: A291

• Zhou M.
• et al.

Development of a functional glomerulus at the organ level on a chip to mimic hypertensive nephropathy.

Sci. Rep. 2016; 6: 31771

• Kim H.J.
• et al.

Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow.

Lab Chip. 2012; 12: 2165-2174

• Wang E.Y.
• et al.

Biowire model of interstitial and focal cardiac fibrosis.

ACS Central Sci. 2019; 5: 1146-1158

• Wang E.Y.
• et al.

Intersection of stem cell biology and engineering towards next generation in vitro models of human fibrosis.

Front Bioeng. Biotechnol. 2022; 101005051

• Graney P.L.
• et al.

Macrophages of diverse phenotypes drive vascularization of engineered tissues.

Sci. Adv. 2020; 6eaay6391

• Lu R.X.Z.
• et al.

Vasculature-on-a-chip platform with innate immunity enables identification of angiopoietin-1 derived peptide as a therapeutic for SARS-CoV-2 induced inflammation.

Lab Chip. 2022; 22: 1171-1186

• Tsui J.H.
• et al.

Tunable electroconductive decellularized extracellular matrix hydrogels for engineering human cardiac microphysiological systems.

Biomaterials. 2021; 272120764

• Schwan J.
• et al.

Anisotropic engineered heart tissue made from laser-cut decellularized myocardium.

Sci. Rep. 2016; 6: 32068

• Cuvellier M.
• et al.

3D culture of HepaRG cells in GelMa and its application to bioprinting of a multicellular hepatic model.

Biomaterials. 2021; 269120611

• Christoffersson J.
• et al.

Fabrication of modular hyaluronan-PEG hydrogels to support 3D cultures of hepatocytes in a perfused liver-on-a-chip device.

Biofabrication. 2019; 11015013

• Lai B.F.L.
• et al.

Recapitulating pancreatic tumor microenvironment through synergistic use of patient organoids and organ-on-a-chip vasculature.

Adv. Funct. Mater. 2020; 302000545

• Langhans S.A.

Three-dimensional in vitro cell culture models in drug discovery and drug repositioning.

Front. Pharmacol. 2018; 9: 6

• Lai B.F.L.
• et al.

A well plate-based multiplexed platform for incorporation of organoids into an organ-on-a-chip system with a perfusable vasculature.

Nat. Protoc. 2021; 16: 2158-2189

• Raj M.
• K. and Chakraborty, S.

PDMS microfluidics: a mini review.

J. Appl. Polym. Sci. 2020; 137: 48958

• Wang J.D.
• et al.

Quantitative analysis of molecular absorption into PDMS microfluidic channels.

Ann. Biomed. Eng. 2012; 40: 1862-1873

• Feinberg A.W.
• Miller J.S.

Progress in three-dimensional bioprinting.

MRS Bull. 2017; 42: 557-562

• Quirós-Solano W.F.
• et al.

Microfabricated tuneable and transferable porous PDMS membranes for organs-on-chips.

Sci. Rep. 2018; 8: 13524

• Xia Y.
• Whitesides G.M.

Soft lithography.

Annu. Rev. Mater. Sci. 1998; 28: 153-184

• Tsao C.-W.

Polymer microfluidics: simple, low-cost fabrication process bridging academic lab research to commercialized production.

Micromachines. 2016; 7: 225

• Gencturk E.
• et al.

Advances in microfluidic devices made from thermoplastics used in cell biology and analyses.

Biomicrofluidics. 2017; 11051502

• Zhao Y.
• et al.

A multimaterial microphysiological platform enabled by rapid casting of elastic microwires.

Adv. Healthc. Mater. 2019; 8e1801187

• Park S.
• Young E.W.K.

E-FLOAT: extractable floating liquid gel-based organ-on-a-chip for airway tissue modeling under airflow.

Adv. Mater. Technol. 2021; 62100828

• Juang Y.J.
• Chiu Y.J.

Fabrication of polymer microfluidics: an overview.

Polymers (Basel). 2022; 14: 2028

• Asmani M.
• et al.

Fibrotic microtissue array to predict anti-fibrosis drug efficacy.

Nat. Commun. 2018; 9: 2066

• Kim M.
• et al.

Multimodal characterization of cardiac organoids using integrations of pressure-sensitive transistor arrays with three-dimensional liquid metal electrodes.

Nano Lett. 2022; 22: 7892-7901

• Melle G.
• et al.

Intracellular recording of human cardiac action potentials on market-available multielectrode array platforms.

Front Bioeng. Biotechnol. 2020; 8: 66

• Imboden M.
• et al.

High-speed mechano-active multielectrode array for investigating rapid stretch effects on cardiac tissue.

Nat. Commun. 2019; 10: 834

• Lauschke V.M.
• et al.

Massive rearrangements of cellular microRNA signatures are key drivers of hepatocyte dedifferentiation.

Hepatology. 2016; 64: 1743-1756

• Gerets H.H.J.
• et al.

Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins.

Cell Biol. Toxicol. 2012; 28: 69-87

• Novik E.I.
• et al.

Augmentation of EB-directed hepatocyte-specific function via collagen sandwich and SNAP.

Biotechnol. Prog. 2008; 24: 1132-1141

• Hamilton G.A.
• et al.

Regulation of cell morphology and cytochrome P450 expression in human hepatocytes by extracellular matrix and cell-cell interactions.

Cell Tissue Res. 2001; 306: 85-99

• Hoffmaster K.A.
• et al.

P-glycoprotein expression, localization, and function in sandwich-cultured primary rat and human hepatocytes: relevance to the hepatobiliary disposition of a model opioid peptide.

Pharm. Res. 2004; 21: 1294-1302

• Khetani S.R.
• Bhatia S.N.

Microscale culture of human liver cells for drug development.

Nat. Biotechnol. 2008; 26: 120-126

• Cho C.H.
• et al.

Layered patterning of hepatocytes in co-culture systems using microfabricated stencils.

Biotechniques. 2010; 48: 47-52

• Lee S.A.
• et al.

Spheroid-based three-dimensional liver-on-a-chip to investigate hepatocyte-hepatic stellate cell interactions and flow effects.

Lab Chip. 2013; 13: 3529-3537

• Toh Y.C.
• et al.

A microfluidic 3D hepatocyte chip for drug toxicity testing.

Lab Chip. 2009; 9: 2026-2035

• Kang Y.B.
• et al.

Liver sinusoid on a chip: Long-term layered co-culture of primary rat hepatocytes and endothelial cells in microfluidic platforms.

Biotechnol. Bioeng. 2015; 112: 2571-2582

• Tan K.
• et al.

A high-throughput microfluidic microphysiological system (PREDICT-96) to recapitulate hepatocyte function in dynamic, re-circulating flow conditions.

Lab Chip. 2019; 19: 1556-1566

• Sung J.H.
• Shuler M.L.

A micro cell culture analog (microCCA) with 3-D hydrogel culture of multiple cell lines to assess metabolism-dependent cytotoxicity of anti-cancer drugs.

Lab Chip. 2009; 9: 1385-1394

• Chen P.-Y.
• et al.

Liver-on-a-chip platform to study anticancer effect of statin and its metabolites.

Biochem. Eng. J. 2021; 165107831

• Skardal A.
• et al.

Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform.

Sci. Rep. 2017; 7: 8837

• Yin F.
• et al.

HiPSC-derived multi-organoids-on-chip system for safety assessment of antidepressant drugs.

Lab Chip. 2021; 21: 571-581

• Kostrzewski T.
• et al.

Three-dimensional perfused human in vitro model of non-alcoholic fatty liver disease.

World J. Gastroenterol. 2017; 23: 204-215

• Skardal A.
• et al.

A reductionist metastasis-on-a-chip platform for in vitro tumor progression modeling and drug screening.

Biotechnol. Bioeng. 2016; 113: 2020-2032

• Kim J.
• et al.

Three-dimensional human liver-chip emulating premetastatic niche formation by breast cancer-derived extracellular vesicles.

ACS Nano. 2020; 14: 14971-14988

• Dvir T.
• et al.

Prevascularization of cardiac patch on the omentum improves its therapeutic outcome.

Proc. Natl. Acad. Sci. U. S. A. 2009; 106: 14990-14995

• Liau B.
• et al.

Pluripotent stem cell-derived cardiac tissue patch with advanced structure and function.

Biomaterials. 2011; 32: 9180-9187

• Stevens K.R.
• et al.

Scaffold-free human cardiac tissue patch created from embryonic stem cells.

Tissue Eng. Part A. 2009; 15: 1211-1222

• Radisic M.
• et al.

High-density seeding of myocyte cells for cardiac tissue engineering.

Biotechnol. Bioeng. 2003; 82: 403-414

• Radisic M.
• et al.

Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds.

Proc. Natl. Acad. Sci. U. S. A. 2004; 101: 18129-18134

• Zimmermann W.H.
• et al.

Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes.

Biotechnol. Bioeng. 2000; 68: 106-114

• Boudou T.
• et al.

A microfabricated platform to measure and manipulate the mechanics of engineered cardiac microtissues.

Tissue Eng. Part A. 2012; 18: 910-919

• Naito H.
• et al.

Optimizing engineered heart tissue for therapeutic applications as surrogate heart muscle.

Circulation. 2006; 114: I72-I78

• Radisic M.
• et al.

Pre-treatment of synthetic elastomeric scaffolds by cardiac fibroblasts improves engineered heart tissue.

J. Biomed. Mater. Res. A. 2007; 86: 713-724

• Mastikhina O.
• et al.

Human cardiac fibrosis-on-a-chip model recapitulates disease hallmarks and can serve as a platform for drug testing.

Biomaterials. 2020; 233119741

• Sadeghi A.H.
• et al.

Engineered 3D cardiac fibrotic tissue to study fibrotic remodeling.

Adv. Healthc. Mater. 2017; 6201601434

• Wang E.Y.
• et al.

Design and fabrication of biological wires for cardiac fibrosis disease modeling.

in: Coulombe K.L.K. Black Iii L.D. Cardiac Tissue Engineering: Methods and Protocols. Springer, 2022: 175-190

• Zimmermann W.H.
• et al.

Tissue engineering of a differentiated cardiac muscle construct.

Circ. Res. 2002; 90: 223-230

• Zimmermann W.H.
• et al.

Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts.

Nat. Med. 2006; 12: 452-458

• Shen S.
• et al.

Physiological calcium combined with electrical pacing accelerates maturation of human engineered heart tissue.

Stem Cell Rep. 2022; 17: 2037-2049

• Lee E.K.
• et al.

Machine learning of human pluripotent stem cell-derived engineered cardiac tissue contractility for automated drug classification.

Stem Cell Rep. 2017; 9: 1560-1572

• Shadrin I.Y.
• et al.

Cardiopatch platform enables maturation and scale-up of human pluripotent stem cell-derived engineered heart tissues.

Nat. Commun. 2017; 8: 1825

• Sidorov V.Y.
• et al.

I-wire heart-on-a-chip I: three-dimensional cardiac tissue constructs for physiology and pharmacology.

Acta Biomater. 2017; 48: 68-78

• Huebsch N.
• et al.

Miniaturized iPS-cell-derived cardiac muscles for physiologically relevant drug response analyses.

Sci. Rep. 2016; 6: 24726

• Schaaf S.
• et al.

Human engineered heart tissue as a versatile tool in basic research and preclinical toxicology.

PLoS One. 2011; 6e26397

• Mathur A.
• et al.

Human iPSC-based cardiac microphysiological system for drug screening applications.

Sci. Rep. 2015; 5: 8883

• King O.
• et al.

Functional microvascularization of human myocardium in vitro.

Cell Rep. Methods. 2022; 2100280

• Ng R.
• et al.

Shortening velocity causes myosin isoform shift in human engineered heart tissues.

Circ. Res. 2021; 128: 281-283

• Nunes S.S.
• et al.

Biowire: a platform for maturation of human pluripotent stem cell-derived cardiomyocytes.

Nat. Methods. 2013; 10: 781-787

• Grosberg A.
• et al.

Ensembles of engineered cardiac tissues for physiological and pharmacological study: heart on a chip.

Lab Chip. 2011; 11: 4165-4173

• Agarwal A.
• et al.

Microfluidic heart on a chip for higher throughput pharmacological studies.

Lab Chip. 2013; 13: 3599-3608

• Ahn S.
• et al.

Mussel-inspired 3D fiber scaffolds for heart-on-a-chip toxicity studies of engineered nanomaterials.

Anal. Bioanal. Chem. 2018; 410: 6141-6154

• Williams R.R.
• et al.

NHLBI family blood pressure program: methodology and recruitment in the HyperGEN network. Hypertension genetic epidemiology network.

Ann. Epidemiol. 2000; 10: 389-400

• Wang E.Y.
• et al.

An organ-on-a-chip model for pre-clinical drug evaluation in progressive non-genetic cardiomyopathy.

J. Mol. Cell. Cardiol. 2021; 160: 97-110

• Kuzmanov U.
• et al.

Mapping signalling perturbations in myocardial fibrosis via the integrative phosphoproteomic profiling of tissue from diverse sources.

Nat. Biomed. Eng. 2020; 4: 889-900

• Ma Z.
• et al.

Contractile deficits in engineered cardiac microtissues as a result of MYBPC3 deficiency and mechanical overload.

Nat. Biomed. Eng. 2018; 2: 955-967

• Takebe T.
• et al.

Synergistic engineering: organoids meet organs-on-a-chip.

Cell Stem Cell. 2017; 21: 297-300

• Tonon F.
• et al.

In vitro metabolic zonation through oxygen gradient on a chip.

Sci. Rep. 2019; 9: 13557

• Kang Y.B.
• et al.

Metabolic patterning on a chip – towards in vitro liver zonation of primary rat and human hepatocytes.

Sci. Rep. 2018; 8: 8951

• Michaels Y.S.
• et al.

DLL4 and VCAM1 enhance the emergence of T cell-competent hematopoietic progenitors from human pluripotent stem cells.

Sci. Adv. 2022; 8eabn5522

• Ronaldson-Bouchard K.
• et al.

A multi-organ chip with matured tissue niches linked by vascular flow.

Nat. Biomed. Eng. 2022; 6: 351-371

• Ahrens J.H.
• et al.

Programming cellular alignment in engineered cardiac tissue via bioprinting anisotropic organ building blocks.

Adv. Mater. 2022; 342200217

• Ma X.
• et al.

Rapid 3D bioprinting of decellularized extracellular matrix with regionally varied mechanical properties and biomimetic microarchitecture.

Biomaterials. 2018; 185: 310-321

FDA Modernization Act of 2021.

117th Congress. 2021–2022

• Nerem R.M.

Regenerative medicine: the emergence of an industry.

J. R. Soc. Interface. 2010; 7: S771-S775

• Vacanti J.P.
• Langer R.

Tissue engineering: the design and fabrication of living replacement devices for surgical reconstruction and transplantation.

Lancet. 1999; 354: st32-st34

• Xia Y.
• Whitesides G.M.

Soft Lithography.

Angew. Chem. Int. Ed. 1998; 37: 550-575

• Radisic M.
• et al.

Biomimetic approach to cardiac tissue engineering: oxygen carriers and channeled scaffolds.

Tissue Eng. 2006; 12: 2077-2091

• Radisic M.
• et al.

Mathematical model of oxygen distribution in engineered cardiac tissue with parallel channel array perfused with culture medium containing oxygen carriers.

Am. J. Physiol. Heart Circ. Physiol. 2005; 288: H1278-H1289

• Lee J.
• et al.

Organoid model in idiopathic pulmonary fibrosis.

Int. J. Stem Cells. 2021; 14: 1-8

• Shin Y.J.
• et al.

3D bioprinting of mechanically tuned bioinks derived from cardiac decellularized extracellular matrix.

Acta Biomater. 2021; 119: 75-88

• Lin Y.
• et al.

Soft lithography based on photolithography and two-photon polymerization.

Microfluid. Nanofluid. 2018; 22: 97