Microfluidic On-Chip Biomimicry for 3D Cell Culture: a Fit-For-Purpose Investigation From the End User Standpoint

References

• Hay M, Thomas DW, Craighead JL, Economides C, Rosenthal J. Clinical development success rates for investigational drugs. Nat. Biotech. 32(1), 40–51 (2014).
   PubMed Web of Science ®Google Scholar
• Begley CG, Ellis LM. Drug development: raise standards for preclinical cancer research. Nature 483(7391), 531–533 (2012).
   PubMed Web of Science ®Google Scholar
• Prinz F, Schlange T, Asadullah K. Believe it or not: how much can we rely on published data on potential drug targets? Nat. Rev. Drug Discov. 10(9), 712 (2011).
   PubMed Web of Science ®Google Scholar
• Hess KR. Statistical design considerations in animal studies published recently in cancer research. Cancer Res. 71(2), 625 (2011).
   PubMed Web of Science ®Google Scholar
• Abbott A. Cell culture: biology's new dimension. Nature 424(6951), 870–872 (2003).
   PubMed Web of Science ®Google Scholar
• Ruggeri BA, Camp F, Miknyoczki S. Animal models of disease: pre-clinical animal models of cancer and their applications and utility in drug discovery. Biochem. Pharmacol. 87(1), 150–161 (2014).
   PubMed Web of Science ®Google Scholar
• Perrin S. Preclinical research: make mouse studies work. Nature 507(7493), 423–425 (2014).
   PubMed Web of Science ®Google Scholar
• Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 22(3), 659–661 (2008).
   PubMed Web of Science ®Google Scholar
• Kilkenny C, Parsons N, Kadyszewski E et al. Survey of the quality of experimental design, statistical analysis and reporting of research using animals. PLoS ONE 4(11), e7824 (2009).
   PubMed Web of Science ®Google Scholar
• Justice BA, Badr NA, Felder RA. 3D cell culture opens new dimensions in cell-based assays. Drug Discov. Today 14(1), 102–107 (2009).
   PubMed Web of Science ®Google Scholar
• Aubin H, Nichol JW, Hutson CB et al. Directed 3D cell alignment and elongation in microengineered hydrogels. Biomaterials 31(27), 6941–6951 (2010).
   PubMed Web of Science ®Google Scholar
• Tibbitt MW, Anseth KS. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol. Bioeng. 103(4), 655–663 (2009).
   PubMed Web of Science ®Google Scholar
• Heydarkhan-Hagvall S, Schenke-Layland K, Dhanasopon AP et al. Three-dimensional electrospun ECM-based hybrid scaffolds for cardiovascular tissue engineering. Biomaterials 29(19), 2907–2914 (2008).
   PubMed Web of Science ®Google Scholar
• Coburn J, Gibson M, Bandalini PA et al. Biomimetics of the extracellular matrix: an integrated three-dimensional fiber-hydrogel composite for cartilage tissue engineering. Smart Struct. Syst. 7(3), 213–222 (2011).
   PubMed Web of Science ®Google Scholar
• Dittrich PS, Manz A. Lab-on-a-chip: microfluidics in drug discovery. Nat. Rev. Drug Discov. 5(3), 210–218 (2006).
   PubMed Web of Science ®Google Scholar
• Huh D, Torisawa Y, Hamilton GA, Kim HJ, Ingber DE. Microengineered physiological biomimicry: organs-on-chips. Lab Chip 12(12), 2156–2164 (2012).
   PubMed Web of Science ®Google Scholar
• Kang J, Lee DW, Hwang HJ, Yeon S-E, Lee M-Y, Kuh H-J. Mini-pillar array for hydrogel-supported 3D culture and high-content histologic analysis of human tumor spheroids. Lab Chip 16(12), 2265–2276 (2016).
   PubMed Web of Science ®Google Scholar
• Tung Y-C, Hsiao AY, Allen SG, Torisawa Y, Ho M, Takayama S. high throughput 3D spheroid culture and drug testing using a 384 hanging drop array. Analyst 136(3), 473–478 (2011).
   PubMed Web of Science ®Google Scholar
• Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat. Biotech. 32(8), 773–785 (2014).
   PubMed Web of Science ®Google Scholar
• Norotte C, Marga FS, Niklason LE, Forgacs G. Scaffold-free vascular tissue engineering using bioprinting. Biomaterials 30(30), 5910–5917 (2009).
   PubMed Web of Science ®Google Scholar
• Breslin S, O'Driscoll L. Three-dimensional cell culture: the missing link in drug discovery. Drug Discov. Today 18(5–6), 240–249 (2013).
   PubMed Web of Science ®Google Scholar
• Pampaloni F, Reynaud EG, Stelzer EHK. The third dimension bridges the gap between cell culture and live tissue. Nat. Rev. Mol. Cell Biol. 8(10), 839–845 (2007).
   PubMed Web of Science ®Google Scholar
• Ramón-Azcón J, Ahadian S, Obregón R et al. Gelatin methacrylate as a promising hydrogel for 3D microscale organization and proliferation of dielectrophoretically patterned cells. Lab Chip 12(16), 2959–2969 (2012).
   PubMed Web of Science ®Google Scholar
• Pietrzyk-Nivau A, Poirault-Chassac S, Gandrille S et al. Three-dimensional environment sustains hematopoietic stem cell differentiation into platelet-producing megakaryocytes. PLoS ONE 10(8), e0136652 (2015).
   PubMed Web of Science ®Google Scholar
• Horst M, Madduri S, Milleret V, Sulser T, Gobet R, Eberli D. A bilayered hybrid microfibrous PLGA–Acellular matrix scaffold for hollow organ tissue engineering. Biomaterials 34(5), 1537–1545 (2013).
   PubMed Web of Science ®Google Scholar
• Guex AG, Birrer DL, Fortunato G, Tevaearai HT, Giraud MN. Anisotropically oriented electrospun matrices with an imprinted periodic micropattern: a new scaffold for engineered muscle constructs. Biomed. Mater. 8(2), 21001 (2013).
   Web of Science ®Google Scholar
• Cheng Q, Sun Z, Meininger G, Almasri M. PDMS elastic micropost arrays for studying vascular smooth muscle cells. Sensors Actuators B Chem. 188, 1055–1063 (2013).
   PubMed Web of Science ®Google Scholar
• Palchesko RN, Zhang L, Sun Y, Feinberg AW. Development of polydimethylsiloxane substrates with tunable elastic modulus to study cell mechanobiology in muscle and nerve. PLoS ONE 7(12), e51499 (2012).
   PubMed Web of Science ®Google Scholar
• Bratt-Leal AM, Kepple KL, Carpenedo RL, Cooke MT, McDevitt TC. Magnetic manipulation and spatial patterning of multi-cellular stem cell aggregates. Integr. Biol. 3(12), 1224–1232 (2011).
   Google Scholar
• Rutz AL, Hyland KE, Jakus AE, Burghardt WR, Shah RN. A multimaterial bioink method for 3D printing tunable, cell-compatible hydrogels. Adv. Mater. 27(9), 1607–1614 (2015).
   PubMed Web of Science ®Google Scholar
• Cui H, Zhu W, Holmes B, Zhang LG. 3D bioprinting: biologically inspired smart release system based on 3D bioprinted perfused scaffold for vascularized tissue regeneration. Adv. Sci. 3(8), 1600058 (2016).
   Web of Science ®Google Scholar
• Fabiilli ML, Wilson CG, Padilla F, Martín-Saavedra FM, Fowlkes JB, Franceschi RT. Acoustic droplet–hydrogel composites for spatial and temporal control of growth factor delivery and scaffold stiffness. Acta Biomater. 9(7), 7399–7409 (2013).
   PubMed Web of Science ®Google Scholar
• Wylie RG, Ahsan S, Aizawa Y, Maxwell KL, Morshead CM, Shoichet MS. Spatially controlled simultaneous patterning of multiple growth factors in three-dimensional hydrogels. Nat. Mater. 10(10), 799–806 (2011).
   PubMed Web of Science ®Google Scholar
• Liu W, Lipner J, Xie J, Manning CN, Thomopoulos S, Xia Y. Nanofiber scaffolds with gradients in mineral content for spatial control of osteogenesis. ACS Appl. Mater. Interfaces 6(4), 2842–2849 (2014).
   PubMed Web of Science ®Google Scholar
• Baker BM, Trappmann B, Stapleton SC, Toro E, Chen CS. Microfluidics embedded within extracellular matrix to define vascular architectures and pattern diffusive gradients. Lab Chip 13(16), 3246–3252 (2013).
   PubMed Web of Science ®Google Scholar
• Kim BJ, Chu I, Jusuf S et al. Oxygen tension and riboflavin gradients cooperatively regulate the migration of Shewanella oneidensis MR-1 revealed by a hydrogel-based microfluidic device. Front. Microbiol. 7, 1438 (2016).
   PubMed Web of Science ®Google Scholar
• Ma H, Jiang Q, Han S et al. Multicellular tumor spheroids as an in vivo–like tumor model for three-dimensional imaging of chemotherapeutic and nano material cellular penetration. Mol. Imaging 11(6), 2012–7290 (2012).
   Web of Science ®Google Scholar
• Lan S-F, Starly B. Alginate based 3D hydrogels as an in vitro coculture model platform for the toxicity screening of new chemical entities. Toxicol. Appl. Pharmacol. 256(1), 62–72 (2011).
   PubMed Web of Science ®Google Scholar
• Puperi DS, Balaoing LR, O'Connell RW, West JL, Grande-Allen KJ. 3-Dimensional spatially organized PEG-based hydrogels for an aortic valve coculture model. Biomaterials 67, 354–364 (2015).
   PubMed Web of Science ®Google Scholar
• Masoumi N, Annabi N, Assmann A et al. Tri-layered elastomeric scaffolds for engineering heart valve leaflets. Biomaterials 35(27), 7774–7785 (2014).
   PubMed Web of Science ®Google Scholar
• Rossi A, Wistlich L, Heffels K, Walles H, Groll J. Isotropic versus bipolar functionalized biomimetic artificial basement membranes and their evaluation in long-term human cell co-culture. Adv. Healthc. Mater. doi:10.1002/adhm.201600224 (2016) ( Epub ahead of print).
   PubMed Web of Science ®Google Scholar
• Shin Y, Han S, Jeon JS et al. Microfluidic assay for simultaneous culture of multiple cell types on surfaces or within hydrogels. Nat. Protoc. 7(7), 1247–1259 (2012).
   PubMed Web of Science ®Google Scholar
• Yeon JH, Ryu HR, Chung M, Hu QP, Jeon NL. In vitro formation and characterization of a perfusable three-dimensional tubular capillary network in microfluidic devices. Lab Chip 12(16), 2815–2822 (2012).
   PubMed Web of Science ®Google Scholar
• Jeong S-Y, Lee J-H, Shin Y, Chung S, Kuh H-J. coculture of tumor spheroids and fibroblasts in a collagen matrix-incorporated microfluidic chip mimics reciprocal activation in solid tumor microenvironment. PLoS ONE 11(7), e0159013 (2016).
   PubMed Web of Science ®Google Scholar
• Metzger W, Sossong D, Bächle A et al. The liquid overlay technique is the key to formation of coculture spheroids consisting of primary osteoblasts, fibroblasts and endothelial cells. Cytotherapy 13(8), 1000–1012 (2011).
   PubMed Web of Science ®Google Scholar
• Jun Y, Kang AR, Lee JS et al. 3D co-culturing model of primary pancreatic islets and hepatocytes in hybrid spheroid to overcome pancreatic cell shortage. Biomaterials 34(15), 3784–3794 (2013).
   PubMed Web of Science ®Google Scholar
• Xu F, Celli J, Rizvi I, Moon S, Hasan T, Demirci U. A three-dimensional in vitro ovarian cancer coculture model using a high-throughput cell patterning platform. Biotechnol. J. 6(2), 204–212 (2011).
   PubMed Web of Science ®Google Scholar
• Snyder J, Son AR, Hamid Q, Wu H, Sun W. Hetero-cellular prototyping by synchronized multi-material bioprinting for rotary cell culture system. Biofabrication 8(1), 15002 (2016).
   Web of Science ®Google Scholar
• Nguyen LH, Kudva AK, Saxena NS, Roy K. Engineering articular cartilage with spatially-varying matrix composition and mechanical properties from a single stem cell population using a multi-layered hydrogel. Biomaterials 32(29), 6946–6952 (2011).
   PubMed Web of Science ®Google Scholar
• Yang C, DelRio FW, Ma H et al. Spatially patterned matrix elasticity directs stem cell fate. Proc. Natl Acad. Sci. USA 113(31), E4439–E4445 (2016).
   PubMed Web of Science ®Google Scholar
• Zhang Q, Lu H, Kawazoe N, Chen G. Pore size effect of collagen scaffolds on cartilage regeneration. Acta Biomater. 10(5), 2005–2013 (2014).
   PubMed Web of Science ®Google Scholar
• Scaffaro R, Lopresti F, Botta L, Rigogliuso S, Ghersi G. Integration of PCL and PLA in a monolithic porous scaffold for interface tissue engineering. J. Mech. Behav. Biomed. Mater. 63, 303–313 (2016).
   PubMed Web of Science ®Google Scholar
• Huh D, Leslie DC, Matthews BD et al. A human disease model of drug toxicity–induced pulmonary edema in a lung-on-a-chip microdevice. Sci. Transl. Med. 4(159), 159ra147–159ra147 (2012).
   PubMed Web of Science ®Google Scholar
• Solomon DE, Abdel-Raziq A, Vanapalli SA. A stress-controlled microfluidic shear viscometer based on smartphone imaging. Rheology Acta 55(9), 727–738 (2016).
   Web of Science ®Google Scholar
• Montel F, Delarue M, Elgeti J, Vignjevic D, Cappello G, Prost J. Isotropic stress reduces cell proliferation in tumor spheroids. New J. Phys. 14(5), 55008 (2012).
   Google Scholar
• Schuurman W, Khristov V, Pot MW, van Weeren PR, Dhert WJ, Malda J. Bioprinting of hybrid tissue constructs with tailorable mechanical properties. Biofabrication 3(2), 21001 (2011).
   PubMed Web of Science ®Google Scholar
• Lee JW, Choi Y-J, Yong W-J et al. Development of a 3D cell printed construct considering angiogenesis for liver tissue engineering. Biofabrication 8(1), 15007 (2016).
   PubMed Web of Science ®Google Scholar
• Ananthanarayanan B, Kim Y, Kumar S. Elucidating the mechanobiology of malignant brain tumors using a brain matrix-mimetic hyaluronic acid hydrogel platform. Biomaterials 32(31), 7913–7923 (2011).
   PubMed Web of Science ®Google Scholar
• McCoy MG, Seo BR, Choi S, Fischbach C. Collagen I hydrogel microstructure and composition conjointly regulate vascular network formation. Acta Biomater. 44, 200–208 (2016).
   PubMed Web of Science ®Google Scholar
• Xue N, Li X, Bertulli C et al. Rapid patterning of 1-D collagenous topography as an ECM protein fibril platform for image cytometry. PLoS ONE 9(4), e93590 (2014).
   PubMed Web of Science ®Google Scholar
• Christopherson GT, Song H, Mao H-Q. The influence of fiber diameter of electrospun substrates on neural stem cell differentiation and proliferation. Biomaterials 30(4), 556–564 (2009).
   PubMed Web of Science ®Google Scholar
• Lee JS, Romero R, Han YM et al. Placenta-on-a-chip: a novel platform to study the biology of the human placenta. J. Matern. Neonatal Med. 29(7), 1046–1054 (2016).
   PubMed Web of Science ®Google Scholar
• Wallin P, Zandén C, Carlberg B, Erkenstam NH, Liu J, Gold J. A method to integrate patterned electrospun fibers with microfluidic systems to generate complex microenvironments for cell culture applications. Biomicrofluidics 6(2), 24131 (2012).
   PubMed Web of Science ®Google Scholar
• Muranen T, Selfors LM, Worster DT et al. Inhibition of PI3K/mTOR leads to adaptive resistance in matrix-attached cancer cells. Cancer Cell. 21(2), 227–239 (2012).
   PubMed Web of Science ®Google Scholar
• Bao J, Wu Q, Wang Y et al. Enhanced hepatic differentiation of rat bone marrow-derived mesenchymal stem cells in spheroidal aggregate culture on a decellularized liver scaffold. Int. J. Mol. Med. 38(2), 457–465 (2016).
   PubMed Web of Science ®Google Scholar
• Hockaday LA, Kang KH, Colangelo NW et al. Rapid 3D printing of anatomically accurate and mechanically heterogeneous aortic valve hydrogel scaffolds. Biofabrication 4(3), 35005 (2012).
   PubMed Web of Science ®Google Scholar
• Kumar A, Nune KC, Misra RDK. Biological functionality of extracellular matrix-ornamented three-dimensional printed hydroxyapatite scaffolds. J. Biomed. Mater. Res. Part A 104A, 1343–1351 (2016).
   Google Scholar
• Park KM, Gerecht S. Hypoxia-inducible hydrogels. Nat. Commun. 5, 4075 (2014).
   PubMed Web of Science ®Google Scholar
• Wu C, Zhou Y, Fan W et al. Hypoxia-mimicking mesoporous bioactive glass scaffolds with controllable cobalt ion release for bone tissue engineering. Biomaterials 33(7), 2076–2085 (2012).
   PubMed Web of Science ®Google Scholar
• Wang L, Liu W, Wang Y et al. Construction of oxygen and chemical concentration gradients in a single microfluidic device for studying tumor cell–drug interactions in a dynamic hypoxia microenvironment. Lab Chip 13(4), 695–705 (2013).
   PubMed Web of Science ®Google Scholar
• Brennan MD, Rexius-Hall ML, Eddington DT. A 3D-printed oxygen control insert for a 24-well plate. PLoS ONE 10(9), e0137631 (2015).
   PubMed Web of Science ®Google Scholar
• Al-Haque S, Miklas JW, Feric N et al. Hydrogel substrate stiffness and topography interact to induce contact guidance in cardiac fibroblasts. Macromol. Biosci. 12(10), 1342–1353 (2012).
   PubMed Web of Science ®Google Scholar
• Sanen K, Paesen R, Luyck S et al. Label-free mapping of microstructural organisation in self-aligning cellular collagen hydrogels using image correlation spectroscopy. Acta Biomater. 30, 258–264 (2016).
   PubMed Web of Science ®Google Scholar
• Tung C, Ardon F, Fiore AG, Suarez SS, Wu M. Cooperative roles of biological flow and surface topography in guiding sperm migration revealed by a microfluidic model. Lab Chip 14(7), 1348–1356 (2014).
   PubMed Web of Science ®Google Scholar
• Zhou J, Khodakov DA, Ellis AV, Voelcker NH. Surface modification for PDMS-based microfluidic devices. Electrophoresis 33(1), 89–104 (2012).
   PubMed Web of Science ®Google Scholar
• Kapur SK, Wang X, Shang H et al. Human adipose stem cells maintain proliferative, synthetic and multipotential properties when suspension cultured as self-assembling spheroids. Biofabrication 4(2), 25004 (2012).
   Web of Science ®Google Scholar
• Soman P, Chung PH, Zhang AP, Chen S. Digital microfabrication of user-defined 3D microstructures in cell-laden hydrogels. Biotechnol. Bioeng. 110(11), 3038–3047 (2013).
   PubMed Web of Science ®Google Scholar
• Rhee S, Puetzer JL, Mason BN, Reinhart-King CA, Bonassar LJ. 3D bioprinting of spatially heterogeneous collagen constructs for cartilage tissue engineering. ACS Biomater. Sci. Eng. 2(10), 1800–1805 (2016).
   PubMed Web of Science ®Google Scholar
• Soroush F, Zhang T, King DJ et al. A novel microfluidic assay reveals a key role for protein kinase C delta in regulating human neutrophil-endothelium interaction. J. Leukoc. Biol. 100(5), 1027–1035 (2016).
   PubMed Web of Science ®Google Scholar
• Wang X, Phan DTT, Sobrino A, George SC, Hughes CCW, Lee AP. Engineering anastomosis between living capillary networks and endothelial cell-lined microfluidic channels. Lab Chip 16(2), 282–290 (2016).
   PubMed Web of Science ®Google Scholar
• Vulto P, Podszun S, Meyer P, Hermann C, Manz A, Urban GA. Phaseguides: a paradigm shift in microfluidic priming and emptying. Lab Chip 11(9), 1596–1602 (2011).
   PubMed Web of Science ®Google Scholar
• Lane SW, Williams DA, Watt FM. Modulating the stem cell niche for tissue regeneration. Nat. Biotechnol. 32(8), 795–803 (2014).
   PubMed Web of Science ®Google Scholar
• Magin CM, Alge DL, Anseth KS. Bio-inspired 3D microenvironments: a new dimension in tissue engineering. Biomed. Mater. 11(2), 22001 (2016).
   Web of Science ®Google Scholar
• Zdeblick MJ, Barth PP, Angell JB. A microminiature fluidic amplifier. Sensors and Actuators 15(4), 427–433 (1988).
   Web of Science ®Google Scholar
• Verpoorte EMJ, Schoot Van Der BH, Jeanneret S, Manz A, Widmer HM, De Rooij NF. Three-dimensional micro flow manifolds for miniaturized chemical analysis systems. J. Micromech. Microeng. 4(4), 246–256 (1994).
   Web of Science ®Google Scholar
• Frame MDS, Sarelius IH. A system for culture of endothelial cells in 20–50-μm branching tubes. Microcirculation 2(4), 377–385 (1995).
   PubMedGoogle Scholar
• Duffy DC, McDonald JC, Schueller OJA, Whitesides GM. Rapid prototyping of microfluidic systems in poly(dimethylsiloxane). Anal. Chem. 70(23), 4974–4984 (1998).
   PubMed Web of Science ®Google Scholar
• Kinahan DJ, Kearney SM, Kilcawley NA, Early PL, Glynn MT, Ducrée J. Density-gradient mediated band extraction of leukocytes from whole blood using centrifugo-pneumatic siphon valving on centrifugal microfluidic discs. PLoS ONE 11(5), e0155545 (2016).
   PubMed Web of Science ®Google Scholar
• Prabhakarpandian B, Shen M-C, Nichols JB et al. SyM-BBB: a microfluidic blood brain barrier model. Lab Chip 13(6), 1093–1101 (2013).
   PubMed Web of Science ®Google Scholar
• Wu H-W, Hsiao Y-H, Chen C-C, Yet S-F, Hsu C-H. A PDMS-based microfluidic hanging drop chip for embryoid body formation. Molecules 21(7), 882 (2016).
   PubMed Web of Science ®Google Scholar
• Pit AM, Bonestroo S, Wijnperlé D, Duits MHG, Mugele F. Electrode-assisted trapping and release of droplets on hydrophilic patches in a hydrophobic microchannel. Microfluid. Nanofluidics 20(9), 123 (2016).
   Web of Science ®Google Scholar
• Zhao S, Chen Y, Partlow BP et al. Bio-functionalized silk hydrogel microfluidic systems. Biomaterials 93, 60–70 (2016).
   PubMed Web of Science ®Google Scholar
• Liu H, Yu X, Cai B et al. Capture and release of cancer cells using electrospun etchable MnO2 nanofibers integrated in microchannels. Appl. Phys. Lett. 106(9), 93703 (2015).
   Web of Science ®Google Scholar
• Bhatia SN, Ingber DE. Microfluidic organs-on-chips. Nat. Biotech. 32(8), 760–772 (2014).
   PubMed Web of Science ®Google Scholar
• Mosig AS. Organ-on-chip models: new opportunities for biomedical research. Future Sci. OA doi:10.4155/fsoa-2016-0038 (2016) ( Epub ahead of print).
   PubMedGoogle Scholar
• Simon T, Coquerel B, Petit A et al. Direct effect of bevacizumab on glioblastoma cell lines in vitro. Neuromol. Med. 16(4), 752–771 (2014).
   PubMed Web of Science ®Google Scholar
• Demange E, Kassim Y, Petit C et al. Survival of cord blood haematopoietic stem cells in a hyaluronan hydrogel for ex vivo biomimicry. J. Tissue Eng. Regen. Med. 7(11), 901–910 (2013).
   PubMed Web of Science ®Google Scholar
• Vivares A, Salle-Lefort S, Arabeyre-Fabre C et al. Morphological behaviour and metabolic capacity of cryopreserved human primary hepatocytes cultivated in a perfused multiwell device. Xenobiotica 45(1), 29–44 (2015).
   PubMed Web of Science ®Google Scholar
• Domansky K, Inman W, Serdy J, Dash A, Lim MHM, Griffith LG. Perfused multiwell plate for 3D liver tissue engineering. Lab Chip 10(1), 51–58 (2010).
   PubMed Web of Science ®Google Scholar
• Wevers NR, van Vught R, Wilschut KJ et al. high throughput compound evaluation on 3D networks of neurons and glia in a microfluidic platform. Sci. Rep. 6, 38856 (2016).
   PubMed Web of Science ®Google Scholar
• Wilmer MJ, Ng CP, Lanz HL, Vulto P, Suter-Dick L, Masereeuw R. Kidney-on-a-chip technology for drug-induced nephrotoxicity screening. Trends Biotechnol. 34(2), 156–170 (2017).
   Web of Science ®Google Scholar
• Lamberti G, Soroush F, Smith A, Kiani MF, Prabhakarpandian B, Pant K. Adhesion patterns in the microvasculature are dependent on bifurcation angle. Microvasc. Res. 99, 19–25 (2015).
   PubMed Web of Science ®Google Scholar
• Prabhakarpandian B, Shen M-C, Nichols JB et al. Synthetic tumor networks for screening drug delivery systems. J. Control. Release 201, 49–55 (2015).
   PubMed Web of Science ®Google Scholar
• Hendriks DFG, Puigvert LF, Messner S, Mortiz W, Ingelman-Sundberg M. Hepatic 3D spheroid models for the detection and study of compounds with cholestatic liability. Sci. Rep. 6, 35434 (2016).
   PubMed Web of Science ®Google Scholar
• Kermanizadeh A, Lohr M, Roursgaard M et al. Hepatic toxicology following single and multiple exposure of engineered nanomaterials utilising a novel primary human 3D liver microtissue model. Part. Fibre Toxicol. 11, 56 (2014).
   PubMed Web of Science ®Google Scholar
• Norona LM, Nguyen DG, Gerber DA, Presnell SC, LeCluyse EL. Modeling compound-induced fibrogenesis in vitro using three-dimensional bioprinted human liver tissues. Toxicol. Sci. 154(2), 354–367 (2016).
   PubMed Web of Science ®Google Scholar
• Nguyen DG, Funk J, Robbins JB et al. Bioprinted 3D primary liver tissues allow assessment of organ-level response to clinical drug induced toxicity in vitro. PLoS ONE 11(7), e0158674 (2016).
   PubMed Web of Science ®Google Scholar
• Kim HJ, Huh D, Hamilton G, Ingber DE. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab Chip 12(12), 2165–2174 (2012).
   PubMed Web of Science ®Google Scholar
• Jang K-J, Mehr AP, Hamilton GA et al. Human kidney proximal tubule-on-a-chip for drug transport and nephrotoxicity assessment. Integr. Biol. (Camb.) 5(9), 1119–1129 (2013).
   PubMed Web of Science ®Google Scholar
• Maschmeyer I, Lorenz AK, Schimek K et al. A four-organ-chip for interconnected long-term coculture of human intestine, liver, skin and kidney equivalents. Lab Chip 15(12), 2688–2699 (2015).
   PubMed Web of Science ®Google Scholar
• Berdichevsky Y, Staley KJ, Yarmush ML. Building and manipulating neural pathways with microfluidics. Lab Chip 10(8), 999–1004 (2010).
   PubMed Web of Science ®Google Scholar
• Han S, Yang K, Shin Y et al. Three-dimensional extracellular matrix-mediated neural stem cell differentiation in a microfluidic device. Lab Chip 12(13), 2305–2308 (2012).
   PubMed Web of Science ®Google Scholar
• Luni C, Serena E, Elvassore N. Human-on-chip for therapy development and fundamental science. Curr. Opin. Biotechnol. 25, 45–50 (2014).
   PubMed Web of Science ®Google Scholar
• Ballabh P, Braun A, Nedergaard M. The blood–brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol. Dis. 16(1), 1–13 (2004).
   PubMed Web of Science ®Google Scholar
• Hislop AA. Airway and blood vessel interaction during lung development. J. Anat. 201(4), 325–334 (2002).
   PubMed Web of Science ®Google Scholar
• Mueller CB. The structure of the renal glomerulus. Am. Heart J. 55(2), 304–322 (1958).
   PubMed Web of Science ®Google Scholar
• Ohayon J, Finet G, Gharib AM et al. Necrotic core thickness and positive arterial remodeling index: emergent biomechanical factors for evaluating the risk of plaque rupture. Am. J. Physiol. Circ. Physiol. 295(2), H717–H727 (2008).
   PubMed Web of Science ®Google Scholar
• Magrini E, Villa A, Angiolini F et al. Endothelial deficiency of L1 reduces tumor angiogenesis and promotes vessel normalization. J. Clin. Invest. 124(10), 4335–4350 (2014).
   PubMed Web of Science ®Google Scholar
• Lee J-H, Bhang DH, Beede A et al. Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-thrombospondin-1 axis. Cell 156(3), 440–455 (2014).
   PubMed Web of Science ®Google Scholar
• Kubota T, Kubota N, Kadowaki T. The role of endothelial insulin signaling in the regulation of glucose metabolism. Rev. Endocr. Metab. Disord. 14(2), 207–216 (2013).
   PubMed Web of Science ®Google Scholar
• Belcher JD, Chen C, Nguyen J et al. The fucosylation inhibitor, 2-fluorofucose, inhibits vaso-occlusion, leukocyte–endothelium interactions and NF-ĸB activation in transgenic sickle mice. PLoS ONE 10(2), e0117772 (2015).
   PubMed Web of Science ®Google Scholar
• Gerdes N, Seijkens T, Lievens D et al. Platelet CD40 exacerbates atherosclerosis by transcellular activation of endothelial cells and leukocytes. Arterioscler. Thromb. Vasc. Biol. 36(3), 482–490 (2016).
   PubMed Web of Science ®Google Scholar
• Muller WA. How endothelial cells regulate transmigration of leukocytes in the inflammatory response. Am. J. Pathol. 184(4), 886–896 (2014).
   PubMed Web of Science ®Google Scholar
• Huveneers S, Daemen MJAP, Hordijk PL. Between rho (k) and a hard place: the relation between vessel wall stiffness, endothelial contractility, and cardiovascular disease. Circ. Res. 116(5), 895–908 (2015).
   PubMed Web of Science ®Google Scholar
• Harney AS, Arwert EN, Entenberg D, Wang Y, Jones JG, Condeelis JS. Perivascular macrophages induce localized, transient blood vessel permeability and tumor cell intravasation. Cancer Res. 74(Suppl. 19), 4940 (2014).
   Web of Science ®Google Scholar
• Correa D, Somoza RA, Lin P, Schiemann WP, Caplan AI. Mesenchymal stem cells regulate melanoma cancer cells extravasation to bone and liver at their perivascular niche. Int. J. Cancer 138(2), 417–427 (2016).
   PubMed Web of Science ®Google Scholar
• Farahat WA, Wood LB, Zervantonakis IK et al. Ensemble analysis of angiogenic growth in three-dimensional microfluidic cell cultures. PLoS ONE 7(5), e37333 (2012).
   PubMed Web of Science ®Google Scholar
• Bogorad MI, DeStefano J, Karlsson J, Wong AD, Gerecht S, Searson PC. Review: in vitro microvessel models. Lab Chip 15(22), 4242–4255 (2015).
   PubMed Web of Science ®Google Scholar
• Tsai M, Kita A, Leach J et al. In vitro modeling of the microvascular occlusion and thrombosis that occur in hematologic diseases using microfluidic technology. J. Clin. Invest. 122(1), 408–418 (2012).
   PubMed Web of Science ®Google Scholar
• Chung S, Sudo R, Vickerman V, Zervantonakis IK, Kamm RD. Microfluidic platforms for studies of angiogenesis, cell migration, and cell–cell interactions. Ann. Biomed. Eng. 38(3), 1164–1177 (2010).
   PubMed Web of Science ®Google Scholar
• Businaro L, De Ninno A, Schiavoni G et al. Cross talk between cancer and immune cells: exploring complex dynamics in a microfluidic environment. Lab Chip 13(2), 229–239 (2013).
   PubMed Web of Science ®Google Scholar
• Buchanan CF, Verbridge SS, Vlachos PP, Rylander MN. Flow shear stress regulates endothelial barrier function and expression of angiogenic factors in a 3D microfluidic tumor vascular model. Cell Adh. Migr. 8(5), 517–524 (2014).
   PubMed Web of Science ®Google Scholar
• Zervantonakis IK, Hughes-Alford SK, Charest JL, Condeelis JS, Gertler FB, Kamm RD. Three-dimensional microfluidic model for tumor cell intravasation and endothelial barrier function. Proc. Natl Acad. Sci. USA 109(34), 13515–13520 (2012).
   PubMed Web of Science ®Google Scholar
• Zheng Y, Chen J, Craven M et al. In vitro microvessels for the study of angiogenesis and thrombosis. Proc. Natl Acad. Sci. USA 109(24), 9342–9347 (2012).
   PubMed Web of Science ®Google Scholar
• Wong KHK, Chan JM, Kamm RD, Tien J. Microfluidic models of vascular functions. Annu. Rev. Biomed. Eng. 14(1), 205–230 (2012).
   PubMed Web of Science ®Google Scholar
• Traktuev DO, Merfeld-Clauss S, Li J et al. A population of multipotent CD34-positive adipose stromal cells share pericytes and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circ. Res. 102(1), 77–85 (2008).
   PubMed Web of Science ®Google Scholar
• Hughes CCW. Endothelial–stromal interactions in angiogenesis. Curr. Opin. Hematol. 15(3), 204–209 (2008).
   PubMed Web of Science ®Google Scholar
• Miller JS, Stevens KR, Yang MT et al. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat. Mater. 11(9), 768–774 (2012).
   PubMed Web of Science ®Google Scholar
• Borenstein JT, Tupper MM, Mack PJ et al. Functional endothelialized microvascular networks with circular cross-sections in a tissue culture substrate. Biomed. Microdevices 12(1), 71–79 (2010).
   PubMed Web of Science ®Google Scholar
• Bischel LL, Young EWK, Mader BR, Beebe DJ. Tubeless microfluidic angiogenesis assay with three-dimensional endothelial-lined microvessels. Biomaterials 34(5), 1471–1477 (2013).
   PubMed Web of Science ®Google Scholar
• Wong AD, Searson PC. Live-cell imaging of invasion and intravasation in an artificial microvessel platform. Cancer Res. 74(17), 4937–4945 (2014).
   PubMed Web of Science ®Google Scholar
• Sarig-Nadir O, Livnat N, Zajdman R, Shoham S, Seliktar D. Laser photoablation of guidance microchannels into hydrogels directs cell growth in three dimensions. Biophys. J. 96(11), 4743–4752 (2009).
   PubMed Web of Science ®Google Scholar
• Hasan A, Paul A, Memic A, Khademhosseini A. A multilayered microfluidic blood vessel-like structure. Biomed. Microdevices 17(5), 88 (2015).
   PubMed Web of Science ®Google Scholar
• Mannino R, Myers DR, Ahn B et al. Vascular geometry and flow profile mediate pathological cell–cell interactions in sickle cell disease as measured with “do-it-yourself” “endothelial-ized” microfluidics. Blood 124(21), 454 (2014).
   Web of Science ®Google Scholar
• Hasan A, Paul A, Vrana NE et al. Microfluidic techniques for development of 3D vascularized tissue. Biomaterials 35(26), 7308–7325 (2014).
   PubMed Web of Science ®Google Scholar
• Nguyen D-HT, Stapleton SC, Yang MT et al. Biomimetic model to reconstitute angiogenic sprouting morphogenesis in vitro. Proc. Natl Acad. Sci. USA 110(17), 6712–6717 (2013).
   PubMed Web of Science ®Google Scholar
• Sackmann EK, Fulton AL, Beebe DJ. The present and future role of microfluidics in biomedical research. Nature 507(7491), 181–189 (2014).
   PubMed Web of Science ®Google Scholar
• Villasante A, Vunjak-Novakovic G. Tissue-engineered models of human tumors for cancer research. Expert Opin. Drug Discov. 10(3), 257–268 (2015).
   PubMed Web of Science ®Google Scholar
• Peng W, Unutmaz D, Ozbolat IT. Bioprinting towards physiologically relevant tissue models for pharmaceutics. Trends Biotechnol. 34(9), 722–732 (2016).
   PubMed Web of Science ®Google Scholar
• Wan ACA. Recapitulating cell–cell interactions for organoid construction – are biomaterials dispensable? Trends Biotechnol. 34(9), 711–721 (2016).
   PubMed Web of Science ®Google Scholar
• Kellogg RA, Gómez-Sjöberg R, Leyrat AA, Tay S. high throughput microfluidic single-cell analysis pipeline for studies of signaling dynamics. Nat. Protoc. 9(7), 1713–1726 (2014).
   PubMed Web of Science ®Google Scholar
• Hughes AJ, Spelke DP, Xu Z, Kang C-C, Schaffer DV, Herr AE. Single-cell western blotting. Nat. Meth. 11(7), 749–755 (2014).
   PubMed Web of Science ®Google Scholar
• Shih SCC, Barbulovic-Nad I, Yang X, Fobel R, Wheeler AR. Digital microfluidics with impedance sensing for integrated cell culture andanalysis. Biosens. Bioelectron. 42, 314–320 (2013).
   PubMed Web of Science ®Google Scholar
• Huh D, Kim HJ, Fraser JP et al. Microfabrication of human organs-on-chips. Nat. Protoc. 8(11), 2135–2157 (2013).
   PubMed Web of Science ®Google Scholar
• Young EWK, Berthier E, Guckenberger DJ et al. Rapid prototyping of arrayed microfluidic systems in polystyrene for cell-based assays. Anal. Chem. 83(4), 1408–1417 (2011).
   PubMed Web of Science ®Google Scholar
• Knowlton S, Yenilmez B, Tasoglu S. Towards single-step biofabrication of organs on a chip via 3D printing. Trends Biotechnol. 34(9), 685–688 (2017).
   Web of Science ®Google Scholar
• Fitzgerald KA, Guo J, Raftery RM et al. Nanoparticle-mediated siRNA delivery assessed in a 3D coculture model simulating prostate cancer bone metastasis. Int. J. Pharm. 511(2), 1058–1069 (2016).
   PubMedGoogle Scholar
• Xu Z, Li E, Guo Z et al. Design and construction of a multi-organ microfluidic chip mimicking the in vivo microenvironment of lung cancer metastasis. ACS Appl. Mater. Interfaces 8(39), 25840–25847 (2016).
   PubMed Web of Science ®Google Scholar
• Kuo C-T, Chiang C-L, Chang C-H et al. Modeling of cancer metastasis and drug resistance via biomimetic nano-cilia and microfluidics. Biomaterials 35(5), 1562–1571 (2014).
   PubMed Web of Science ®Google Scholar
• Mi S, Du Z, Xu Y et al. Microfluidic coculture system for cancer migratory analysis and anti-metastatic drugs screening. Sci. Rep. 6, 35544 (2016).
   PubMed Web of Science ®Google Scholar
• Sung JH, Shuler ML. 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 9(10), 1385–1394 (2009).
   PubMed Web of Science ®Google Scholar
• Tomlinson RE, Li Z, Zhang Q et al. NGF-TrkA signaling by sensory nerves coordinates the vascularization and ossification of developing endochondral bone. Cell Rep. 16(10), 2723–2735 (2016).
   PubMed Web of Science ®Google Scholar