Skip to main content
SpringerLink
Log in

New Frontiers in Cardiovascular Research: Microfluidic Modeling of Cardiovascular Diseases and Applications for Hypertension Research

  • Chapter
  • First Online:
Management of Hypertension

  • 1139 Accesses

Abstract

Microfluidic organ-on-chips are rapidly emerging as viable and informative platforms for disease modeling and drug development. A central advantage of these platforms is the integration of biophysical stimuli with biological components to aid in recreating the microenvironment of cells, tissues, and organs. By doing so, microfluidic organ-on-chips may more closely approximate (patho)physiological events and drug responses in humans than traditional cell cultures and animal models. This chapter provides a general overview of microfluidic organ-on-chips for cardiovascular research, and discusses current and future applications to hypertension research. This chapter is intended as a primer for clinicians interested in basic science/translational research of CVDs.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Huh D, Leslie DC, Matthews BD, Fraser JP, Jurek S, Hamilton GA, et al. A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice. Sci Transl Med. 2012;4(159):159ra47.

    Article  Google Scholar 

  2. Lee PJ, Hung PJ, Lee LP. An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. Biotechnol Bioeng. 2007;97(5):1340–6.

    Article  CAS  Google Scholar 

  3. 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. 2012;12(12):2165–74.

    Article  CAS  Google Scholar 

  4. Jang KJ, Suh KY. A multi-layer microfluidic device for efficient culture and analysis of renal tubular cells. Lab Chip. 2010;10(1):36–42.

    Article  CAS  Google Scholar 

  5. Vedula EM, Alonso JL, Arnaout MA, Charest JL. A microfluidic renal proximal tubule with active reabsorptive function. PLoS One. 2017;12(10):e0184330.

    Article  Google Scholar 

  6. Jusoh N, Oh S, Kim S, Kim J, Jeon NL. Microfluidic vascularized bone tissue model with hydroxyapatite-incorporated extracellular matrix. Lab Chip. 2015;15(20):3984–8.

    Article  CAS  Google Scholar 

  7. Kilic O, Pamies D, Lavell E, Schiapparelli P, Feng Y, Hartung T, et al. Brain-on-a-chip model enables analysis of human neuronal differentiation and chemotaxis. Lab Chip. 2016;16(21):4152–62.

    Article  CAS  Google Scholar 

  8. Mathur A, Loskill P, Shao K, Huebsch N, Hong S, Marcus SG, et al. Human iPSC-based cardiac microphysiological system for drug screening applications. Sci Rep. 2015;5:8883.

    Article  CAS  Google Scholar 

  9. Smith Q, Gerecht S. Going with the flow: microfluidic platforms in vascular tissue engineering. Curr Opin Chem Eng. 2014;3:42–50.

    Article  Google Scholar 

  10. Prantil-Baun R, Novak R, Das D, Somayaji MR, Przekwas A, Ingber DE. Physiologically based pharmacokinetic and Pharmacodynamic analysis enabled by microfluidically linked organs-on-chips. Annu Rev Pharmacol Toxicol. 2018;58:37–64.

    Article  CAS  Google Scholar 

  11. Scannell JW, Blanckley A, Boldon H, Warrington B. Diagnosing the decline in pharmaceutical R&D efficiency. Nat Rev Drug Discov. 2012;11(3):191–200.

    Article  CAS  Google Scholar 

  12. Sackmann EK, Fulton AL, Beebe DJ. The present and future role of microfluidics in biomedical research. Nature. 2014;507(7491):181–9.

    Article  CAS  Google Scholar 

  13. Ribas J, Sadeghi H, Manbachi A, Leijten J, Brinegar K, Zhang YS, et al. Cardiovascular organ-on-a-chip platforms for drug discovery and development. Appl In Vitro Toxicol. 2016;2(2):82–96.

    Article  Google Scholar 

  14. Barnard ND, Kaufman SR. Animal research is wasteful and misleading. Sci Am. 1997;276(2):80–2.

    Article  CAS  Google Scholar 

  15. Wang YI, Abaci HE, Shuler ML. Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening. Biotechnol Bioeng. 2017;114(1):184–94.

    Article  CAS  Google Scholar 

  16. Moya ML, Hsu YH, Lee AP, Hughes CC, George SC. In vitro perfused human capillary networks. Tissue Eng Part C Methods. 2013;19(9):730–7.

    Article  CAS  Google Scholar 

  17. Baeyens N, Bandyopadhyay C, Coon BG, Yun S, Schwartz MA. Endothelial fluid shear stress sensing in vascular health and disease. J Clin Invest. 2016;126(3):821–8.

    Article  Google Scholar 

  18. Polacheck WJ, Li R, Uzel SG, Kamm RD. Microfluidic platforms for mechanobiology. Lab Chip. 2013;13(12):2252–67.

    Article  CAS  Google Scholar 

  19. Tarbell JM. Shear stress and the endothelial transport barrier. Cardiovasc Res. 2010;87(2):320–30.

    Article  CAS  Google Scholar 

  20. White J, Lancelot M, Sarnaik S, Hines P. Increased erythrocyte adhesion to VCAM-1 during pulsatile flow: application of a microfluidic flow adhesion bioassay. Clin Hemorheol Microcirc. 2015;60(2):201–13.

    Article  CAS  Google Scholar 

  21. Hsu YH, Moya ML, Abiri P, Hughes CC, George SC, Lee AP. Full range physiological mass transport control in 3D tissue cultures. Lab Chip. 2013;13(1):81–9.

    Article  CAS  Google Scholar 

  22. Chin LK, Yu JQ, Fu Y, Yu T, Liu AQ, Luo KQ. Production of reactive oxygen species in endothelial cells under different pulsatile shear stresses and glucose concentrations. Lab Chip. 2011;11(11):1856–63.

    Article  CAS  Google Scholar 

  23. Wang L, Xiang M, Liu Y, Sun N, Lu M, Shi Y, et al. Human induced pluripotent stem cells derived endothelial cells mimicking vascular inflammatory response under flow. Biomicrofluidics. 2016;10(1):014106.

    Article  Google Scholar 

  24. Punchard MA, Stenson-Cox C, O’Cearbhaill ED, Lyons E, Gundy S, Murphy L, et al. Endothelial cell response to biomechanical forces under simulated vascular loading conditions. J Biomech. 2007;40(14):3146–54.

    Article  CAS  Google Scholar 

  25. Zheng W, Jiang B, Wang D, Zhang W, Wang Z, Jiang X. A microfluidic flow-stretch chip for investigating blood vessel biomechanics. Lab Chip. 2012;12(18):3441–50.

    Article  CAS  Google Scholar 

  26. Collins NT, Cummins PM, Colgan OC, Ferguson G, Birney YA, Murphy RP, et al. Cyclic strain-mediated regulation of vascular endothelial occludin and ZO-1: influence on intercellular tight junction assembly and function. Arterioscler Thromb Vasc Biol. 2006;26(1):62–8.

    Article  CAS  Google Scholar 

  27. Partyka PP, Godsey GA, Galie JR, Kosciuk MC, Acharya NK, Nagele RG, et al. c. Biomaterials. 2017;115:30–9.

    Article  CAS  Google Scholar 

  28. Sinha R, Le Gac S, Verdonschot N, van den Berg A, Koopman B, Rouwkema J. Endothelial cell alignment as a result of anisotropic strain and flow induced shear stress combinations. Sci Rep. 2016;6:29510.

    Article  CAS  Google Scholar 

  29. Triggle CR, Samuel SM, Ravishankar S, Marei I, Arunachalam G, Ding H. The endothelium: influencing vascular smooth muscle in many ways. Can J Physiol Pharmacol. 2012;90(6):713–38.

    Article  CAS  Google Scholar 

  30. Sandow SL, Bramich NJ, Bandi HP, Rummery NM, Hill CE. Structure, function, and endothelium-derived hyperpolarizing factor in the caudal artery of the SHR and WKY rat. Arterioscler Thromb Vasc Biol. 2003;23(5):822–8.

    Article  CAS  Google Scholar 

  31. Armulik A, Genove G, Betsholtz C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell. 2011;21(2):193–215.

    Article  CAS  Google Scholar 

  32. Pfister F, Przybyt E, Harmsen MC, Hammes HP. Pericytes in the eye. Pflugers Arch. 2013;465(6):789–96.

    Article  CAS  Google Scholar 

  33. Heidi AHT, Cui B, Chu ZE, Veres T, Radisic M. Cell culture chips for simultaneous application of topographical and electrical cues enhance phenotype of cardiomyocytes. Lab Chip. 2009;9(4):564–75.

    Article  Google Scholar 

  34. Sheehy SP, Grosberg A, Qin P, Behm DJ, Ferrier JP, Eagleson MA, et al. Toward improved myocardial maturity in an organ-on-chip platform with immature cardiac myocytes. Exp Biol Med (Maywood). 2017;242(17):1643–56.

    Article  CAS  Google Scholar 

  35. Annabi N, Selimovic S, Acevedo Cox JP, Ribas J, Afshar Bakooshli M, Heintze D, et al. Hydrogel-coated microfluidic channels for cardiomyocyte culture. Lab Chip. 2013;13(18):3569–77.

    Article  CAS  Google Scholar 

  36. Feinberg AW, Feigel A, Shevkoplyas SS, Sheehy S, Whitesides GM, Parker KK. Muscular thin films for building actuators and powering devices. Science. 2007;317(5843):1366–70.

    Article  CAS  Google Scholar 

  37. Boothe SD, Myers JD, Pok S, Sun J, Xi Y, Nieto RM, et al. The effect of substrate stiffness on Cardiomyocyte action potentials. Cell Biochem Biophys. 2016;74(4):527–35.

    Article  CAS  Google Scholar 

  38. Ruan JL, Tulloch NL, Razumova MV, Saiget M, Muskheli V, Pabon L, et al. Mechanical stress conditioning and electrical stimulation promote contractility and force maturation of induced pluripotent stem cell-derived human cardiac tissue. Circulation. 2016;134(20):1557–67.

    Article  CAS  Google Scholar 

  39. Xiao Y, Zhang B, Liu H, Miklas JW, Gagliardi M, Pahnke A, et al. Microfabricated perfusable cardiac biowire: a platform that mimics native cardiac bundle. Lab Chip. 2014;14(5):869–82.

    Article  CAS  Google Scholar 

  40. Marsano A, Conficconi C, Lemme M, Occhetta P, Gaudiello E, Votta E, et al. Beating heart on a chip: a novel microfluidic platform to generate functional 3D cardiac microtissues. Lab Chip. 2016;16(3):599–610.

    Article  CAS  Google Scholar 

  41. Khanal G, Chung K, Solis-Wever X, Johnson B, Pappas D. Ischemia/reperfusion injury of primary porcine cardiomyocytes in a low-shear microfluidic culture and analysis device. Analyst. 2011;136(17):3519–26.

    Article  CAS  Google Scholar 

  42. Ren L, Liu W, Wang Y, Wang JC, Tu Q, Xu J, et al. Investigation of hypoxia-induced myocardial injury dynamics in a tissue interface mimicking microfluidic device. Anal Chem. 2013;85(1):235–44.

    Article  CAS  Google Scholar 

  43. McCain ML, Sheehy SP, Grosberg A, Goss JA, Parker KK. Recapitulating maladaptive, multiscale remodeling of failing myocardium on a chip. Proc Natl Acad Sci U S A. 2013;110(24):9770–5.

    Article  CAS  Google Scholar 

  44. Wang G, McCain ML, Yang L, He A, Pasqualini FS, Agarwal A, et al. Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies. Nat Med. 2014;20(6):616–23.

    Article  CAS  Google Scholar 

  45. Dharmashankar K, Widlansky ME. Vascular endothelial function and hypertension: insights and directions. Curr Hypertens Rep. 2010;12(6):448–55.

    Article  Google Scholar 

  46. Brandes RP. Endothelial dysfunction and hypertension. Hypertension. 2014;64(5):924–8.

    Article  CAS  Google Scholar 

  47. Chen Y, Chan HN, Michael SA, Shen Y, Chen Y, Tian Q, et al. A microfluidic circulatory system integrated with capillary-assisted pressure sensors. Lab Chip. 2017;17(4):653–62.

    Article  Google Scholar 

  48. Simara P, Tesarova L, Rehakova D, Farkas S, Salingova B, Kutalkova K, et al. Reprogramming of adult peripheral blood cells into human induced pluripotent stem cells as a safe and accessible source of endothelial cells. Stem Cells Dev. 2018;27(1):10–22.

    Article  CAS  Google Scholar 

  49. Gimbrone MA Jr, Garcia-Cardena G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res. 2016;118(4):620–36.

    Article  CAS  Google Scholar 

  50. Estrada R, Giridharan GA, Nguyen MD, Prabhu SD, Sethu P. Microfluidic endothelial cell culture model to replicate disturbed flow conditions seen in atherosclerosis susceptible regions. Biomicrofluidics. 2011;5(3):32006–3200611.

    Article  Google Scholar 

  51. Kim Y, Lobatto ME, Kawahara T, Lee Chung B, Mieszawska AJ, Sanchez-Gaytan BL, et al. Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis. Proc Natl Acad Sci U S A. 2014;111(3):1078–83.

    Article  CAS  Google Scholar 

  52. Menon NV, Tay HM, Pang KT, Dalan R, Wong SC, Wang X, et al. A tunable microfluidic 3D stenosis model to study leukocyte-endothelial interactions in atherosclerosis. APL Bioeng. 2018;2(1) https://doi.org/10.1063/1.4993762.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Mechanical Engineering, Boston University, Boston, MA, USA

    Iason T. Papademetriou

Authors
  1. Iason T. Papademetriou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Iason T. Papademetriou .

Editor information

Editors and Affiliations

  1. Georgetown University and VA Medical Center, Washington, DC, USA

    Vasilios Papademetriou

  2. Fourth Internal Medicine Department, Evangelismos State General Hospital, Athens, Greece

    Emmanuel A. Andreadis

  3. Fourth Internal Medicine Department, Evangelismos State General Hospital, Athens, Greece

    Charalampia Geladari

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Papademetriou, I.T. (2019). New Frontiers in Cardiovascular Research: Microfluidic Modeling of Cardiovascular Diseases and Applications for Hypertension Research. In: Papademetriou, V., Andreadis, E., Geladari, C. (eds) Management of Hypertension. Springer, Cham. https://doi.org/10.1007/978-3-319-92946-0_17

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-92946-0_17

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-92945-3

  • Online ISBN: 978-3-319-92946-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation