Bioprinting Approaches to Engineering Vascularized 3D Cardiac Tissues


Purpose of Review

3D bioprinting technologies hold significant promise for the generation of engineered cardiac tissue and translational applications in medicine. To generate a clinically relevant sized tissue, the provisioning of a perfusable vascular network that provides nutrients to cells in the tissue is a major challenge. This review summarizes the recent vascularization strategies for engineering 3D cardiac tissues.

Recent Findings

Considerable steps towards the generation of macroscopic sizes for engineered cardiac tissue with efficient vascular networks have been made within the past few years. Achieving a compact tissue with enough cardiomyocytes to provide functionality remains a challenging task. Achieving perfusion in engineered constructs with media that contain oxygen and nutrients at a clinically relevant tissue sizes remains the next frontier in tissue engineering.


The provisioning of a functional vasculature is necessary for maintaining a high cell viability and functionality in engineered cardiac tissues. Several recent studies have shown the ability to generate tissues up to a centimeter scale with a perfusable vascular network. Future challenges include improving cell density and tissue size. This requires the close collaboration of a multidisciplinary teams of investigators to overcome complex challenges in order to achieve success.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3


Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.

    Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJL. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet Lond Engl. 2006;367(9524):1747–57.

    Google Scholar 

  2. 2.

    Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. Heart Disease and Stroke Statistics-2019 update: a report from the American Heart Association. Circulation. 2019;31:CIR0000000000000659.

    Google Scholar 

  3. 3.

    Chambers DC, Cherikh WS, Goldfarb SB, Hayes D, Kucheryavaya AY, Toll AE, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: thirty-fifth adult lung and heart-lung transplant report-2018; focus theme: multiorgan transplantation. J Heart Lung Transplant Off Publ Int Soc Heart Transplant. 2018;37(10):1169–83.

    Google Scholar 

  4. 4.

    Zhang YS, Aleman J, Arneri A, Bersini S, Piraino F, Shin SR, et al. From cardiac tissue engineering to heart-on-a-chip: beating challenges. Biomed Mater Bristol Engl. 2015;10(3):034006.

    Google Scholar 

  5. 5.

    Vunjak-Novakovic G, Tandon N, Godier A, Maidhof R, Marsano A, Martens TP, et al. Challenges in cardiac tissue engineering. Tissue Eng Part B Rev. 2010;16(2):169–87.

    PubMed  Google Scholar 

  6. 6.

    Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabé-Heider F, Walsh S, et al. Evidence for cardiomyocyte renewal in humans. Science. 2009;324(5923):98–102.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Kajstura J, Gurusamy N, Ogórek B, Goichberg P, Clavo-Rondon C, Hosoda T, et al. Myocyte turnover in the aging human heart. Circ Res. 2010;107(11):1374–86.

    CAS  PubMed  Google Scholar 

  8. 8.

    Burridge PW, Matsa E, Shukla P, Lin ZC, Churko JM, Ebert AD, et al. Chemically defined generation of human cardiomyocytes. Nat Methods. 2014;11(8):855–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Zhang J, Wilson GF, Soerens AG, Koonce CH, Yu J, Palecek SP, et al. Functional cardiomyocytes derived from human induced pluripotent stem cells. Circ Res. 2009;104(4):e30–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Derakhshanfar S, Mbeleck R, Xu K, Zhang X, Zhong W, Xing M. 3D bioprinting for biomedical devices and tissue engineering: a review of recent trends and advances. Bioact Mater. 2018;3(2):144–56.

    PubMed  PubMed Central  Google Scholar 

  11. 11.

    Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol. 2014;32(8):773–85.

    CAS  PubMed  Google Scholar 

  12. 12.

    Ubil E, Duan J, Pillai ICL, Rosa-Garrido M, Wu Y, Bargiacchi F, et al. Mesenchymal-endothelial transition contributes to cardiac neovascularization. Nature. 2014;514(7524):585–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Sun X, Altalhi W, Nunes SS. Vascularization strategies of engineered tissues and their application in cardiac regeneration. Adv Drug Deliv Rev. 2016;96:183–94.

    CAS  PubMed  Google Scholar 

  14. 14.

    Ali M, Pages E, Ducom A, Fontaine A, Guillemot F. Controlling laser-induced jet formation for bioprinting mesenchymal stem cells with high viability and high resolution. Biofabrication. 2014;6(4):045001.

    PubMed  Google Scholar 

  15. 15.

    Billiet T, Vandenhaute M, Schelfhout J, Van Vlierberghe S, Dubruel P. A review of trends and limitations in hydrogel-rapid prototyping for tissue engineering. Biomaterials. 2012;33(26):6020–41.

    CAS  PubMed  Google Scholar 

  16. 16.

    Gao G, Schilling AF, Hubbell K, Yonezawa T, Truong D, Hong Y, et al. Improved properties of bone and cartilage tissue from 3D inkjet-bioprinted human mesenchymal stem cells by simultaneous deposition and photocrosslinking in PEG-GelMA. Biotechnol Lett. 2015;37(11):2349–55.

    CAS  PubMed  Google Scholar 

  17. 17.

    Ning L, Chen X. A brief review of extrusion-based tissue scaffold bio-printing. Biotechnol J. 2017;12(8).

    Google Scholar 

  18. 18.

    Gou M, Qu X, Zhu W, Xiang M, Yang J, Zhang K, et al. Bio-inspired detoxification using 3D-printed hydrogel nanocomposites. Nat Commun. 2014;5:3774.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Serpooshan V, Mahmoudi M, Hu DA, Hu JB, Wu SM. Bioengineering cardiac constructs using 3D printing. J 3D Print Med. 2017;1(2):123–39.

    CAS  Google Scholar 

  20. 20.

    Hopp B. Femtosecond laser printing of living cells using absorbing film-assisted laser-induced forward transfer. Opt Eng. 2012;51(1):014302.

    Google Scholar 

  21. 21.

    Guillotin B, Souquet A, Catros S, Duocastella M, Pippenger B, Bellance S, et al. Laser assisted bioprinting of engineered tissue with high cell density and microscale organization. Biomaterials. 2010;31(28):7250–6.

    CAS  PubMed  Google Scholar 

  22. 22.

    Nahmias Y, Schwartz RE, Verfaillie CM, Odde DJ. Laser-guided direct writing for three-dimensional tissue engineering. Biotechnol Bioeng. 2005;92(2):129–36.

    CAS  PubMed  Google Scholar 

  23. 23.

    Hölzl K, Lin S, Tytgat L, Van Vlierberghe S, Gu L, Ovsianikov A. Bioink properties before, during and after 3D bioprinting. Biofabrication. 2016;23;8(3):032002.

    Google Scholar 

  24. 24.

    Xu T, Baicu C, Aho M, Zile M, Boland T. Fabrication and characterization of bio-engineered cardiac pseudo tissues. Biofabrication. 2009;1(3):035001.

    PubMed  PubMed Central  Google Scholar 

  25. 25.

    Gruene M, Deiwick A, Koch L, Schlie S, Unger C, Hofmann N, et al. Laser printing of stem cells for biofabrication of scaffold-free autologous grafts. Tissue Eng Part C Methods. 2011;17(1):79–87.

    PubMed  Google Scholar 

  26. 26.

    Calvert P. MATERIALS SCIENCE: printing cells. Science. 2007;318(5848):208–9.

    CAS  PubMed  Google Scholar 

  27. 27.

    Cui X, Boland T. Human microvasculature fabrication using thermal inkjet printing technology. Biomaterials. 2009;30(31):6221–7.

    CAS  PubMed  Google Scholar 

  28. 28.

    Chang CC, Boland ED, Williams SK, Hoying JB. Direct-write bioprinting three-dimensional biohybrid systems for future regenerative therapies. J Biomed Mater Res B Appl Biomater. 2011;98(1):160–70.

    PubMed  PubMed Central  Google Scholar 

  29. 29.

    Okamoto T, Suzuki T, Yamamoto N. Microarray fabrication with covalent attachment of DNA using bubble jet technology. Nat Biotechnol. 2000;18(4):438–41.

    CAS  PubMed  Google Scholar 

  30. 30.

    Goldmann T, Gonzalez JS. DNA-printing: utilization of a standard inkjet printer for the transfer of nucleic acids to solid supports. J Biochem Biophys Methods. 2000;42(3):105–10.

    CAS  PubMed  Google Scholar 

  31. 31.

    Saunders RE, Gough JE, Derby B. Delivery of human fibroblast cells by piezoelectric drop-on-demand inkjet printing. Biomaterials. 2008;29(2):193–203.

    CAS  PubMed  Google Scholar 

  32. 32.

    Cui X, Boland T, D’Lima DD, Lotz MK. Thermal inkjet printing in tissue engineering and regenerative medicine. Recent Pat Drug Deliv Formul. 2012;6(2):149–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Pati F, Jang J, Ha D-H, Won Kim S, Rhie J-W, Shim J-H, et al. Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink. Nat Commun. 2014;5:3935.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Mironov V, Visconti RP, Kasyanov V, Forgacs G, Drake CJ, Markwald RR. Organ printing: tissue spheroids as building blocks. Biomaterials. 2009;30(12):2164–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Kim JD, Choi JS, Kim BS, Chan Choi Y, Cho YW. Piezoelectric inkjet printing of polymers: stem cell patterning on polymer substrates. Polymer. 2010;51(10):2147–54.

    CAS  Google Scholar 

  36. 36.

    Murphy SV, Skardal A, Atala A. Evaluation of hydrogels for bio-printing applications. J Biomed Mater Res A. 2013;101(1):272–84.

    PubMed  Google Scholar 

  37. 37.

    Khalil S, Sun W. Biopolymer deposition for freeform fabrication of hydrogel tissue constructs. Mater Sci Eng C. 2007;27(3):469–78.

    CAS  Google Scholar 

  38. 38.

    Hennink WE, van Nostrum CF. Novel crosslinking methods to design hydrogels. Adv Drug Deliv Rev. 2002;54(1):13–36.

    CAS  PubMed  Google Scholar 

  39. 39.

    Turksen K. Bioprinting in regenerative medicine. Cham Heidelberg New York: Springer; 2015. 140 p. (Stem cell biology and regenerative medicine)

    Google Scholar 

  40. 40.

    Ozbolat IT, Hospodiuk M. Current advances and future perspectives in extrusion-based bioprinting. Biomaterials. 2016;76:321–43.

    CAS  PubMed  Google Scholar 

  41. 41.

    Chang R, Nam J, Sun W. Effects of dispensing pressure and nozzle diameter on cell survival from solid freeform fabrication-based direct cell writing. Tissue Eng Part A. 2008;14(1):41–8.

    CAS  PubMed  Google Scholar 

  42. 42.

    Jones N. Science in three dimensions: the print revolution. Nature. 2012;487(7405):22–3.

    CAS  PubMed  Google Scholar 

  43. 43.

    •• Kolesky DB, Homan KA, Skylar-Scott MA, Lewis JA. Three-dimensional bioprinting of thick vascularized tissues. Proc Natl Acad Sci U S A. 2016;113(12):3179–84. This manuscript shows pioneering work creating thick perfusable tissue.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Irvine SA, Agrawal A, Lee BH, Chua HY, Low KY, Lau BC, et al. Printing cell-laden gelatin constructs by free-form fabrication and enzymatic protein crosslinking. Biomed Microdevices. 2015;17(1):16.

    PubMed  PubMed Central  Google Scholar 

  45. 45.

    Laronda MM, Rutz AL, Xiao S, Whelan KA, Duncan FE, Roth EW, et al. A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice. Nat Commun. 2017;16;8:15261.

    Google Scholar 

  46. 46.

    Gao G, Yonezawa T, Hubbell K, Dai G, Cui X. Inkjet-bioprinted acrylated peptides and PEG hydrogel with human mesenchymal stem cells promote robust bone and cartilage formation with minimal printhead clogging. Biotechnol J. 2015;10(10):1568–77.

    CAS  PubMed  Google Scholar 

  47. 47.

    Schiele NR, Corr DT, Huang Y, Raof NA, Xie Y, Chrisey DB. Laser-based direct-write techniques for cell printing. Biofabrication. 2010;2(3):032001.

    PubMed  PubMed Central  Google Scholar 

  48. 48.

    Duan B, Hockaday LA, Kang KH, Butcher JT. 3D bioprinting of heterogeneous aortic valve conduits with alginate/gelatin hydrogels. J Biomed Mater Res A. 2013;101(5):1255–64.

    PubMed  Google Scholar 

  49. 49.

    Ozbolat IT, Yu Y. Bioprinting toward organ fabrication: challenges and future trends. IEEE Trans Biomed Eng. 2013;60(3):691–9.

    PubMed  Google Scholar 

  50. 50.

    Panwar A, Tan LP. Current status of bioinks for micro-extrusion-based 3D bioprinting. Mol Basel Switz. 2016;25:21(6).

    Google Scholar 

  51. 51.

    Chimene D, Lennox KK, Kaunas RR, Gaharwar AK. Advanced bioinks for 3D printing: a materials science perspective. Ann Biomed Eng. 2016;44(6):2090–102.

    PubMed  Google Scholar 

  52. 52.

    Gopinathan J, Noh I. Recent trends in bioinks for 3D printing. Biomater Res [Internet]. 2018 Dec [cited 2019 Feb 28];22(1). Available from:

  53. 53.

    Tirella A, Orsini A, Vozzi G, Ahluwalia A. A phase diagram for microfabrication of geometrically controlled hydrogel scaffolds. Biofabrication. 2009;1(4):045002.

    CAS  PubMed  Google Scholar 

  54. 54.

    Gudapati H, Dey M, Ozbolat I. A comprehensive review on droplet-based bioprinting: past, present and future. Biomaterials. 2016;102:20–42.

    CAS  PubMed  Google Scholar 

  55. 55.

    Li S, Xiong Z, Wang X, Yan Y, Liu H, Zhang R. Direct fabrication of a hybrid cell/hydrogel construct by a double-nozzle assembling technology. J Bioact Compat Polym. 2009;24(3):249–65.

    Google Scholar 

  56. 56.

    Gaetani R, Feyen DAM, Verhage V, Slaats R, Messina E, Christman KL, et al. Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction. Biomaterials. 2015;61:339–48.

    CAS  PubMed  Google Scholar 

  57. 57.

    Duan B, Kapetanovic E, Hockaday LA, Butcher JT. Three-dimensional printed trileaflet valve conduits using biological hydrogels and human valve interstitial cells. Acta Biomater. 2014;10(5):1836–46.

    CAS  PubMed  Google Scholar 

  58. 58.

    Censi R, van Putten S, Vermonden T, di Martino P, van Nostrum CF, Harmsen MC, et al. The tissue response to photopolymerized PEG-p (HPMAm-lactate)-based hydrogels. J Biomed Mater Res A. 2011;97(3):219–29.

    PubMed  Google Scholar 

  59. 59.

    Schuurman W, Levett PA, Pot MW, van Weeren PR, Dhert WJA, Hutmacher DW, et al. Gelatin-methacrylamide hydrogels as potential biomaterials for fabrication of tissue-engineered cartilage constructs. Macromol Biosci. 2013;13(5):551–61.

    CAS  PubMed  Google Scholar 

  60. 60.

    Stanton MM, Samitier J, Sánchez S. Bioprinting of 3D hydrogels. Lab Chip. 2015;15(15):3111–5.

    CAS  PubMed  Google Scholar 

  61. 61.

    Hoffman AS. Hydrogels for biomedical applications. Adv Drug Deliv Rev. 2002;54(1):3–12.

    CAS  PubMed  Google Scholar 

  62. 62.

    Jose RR, Rodriguez MJ, Dixon TA, Omenetto F, Kaplan DL. Evolution of bioinks and additive manufacturing technologies for 3D bioprinting. ACS Biomater Sci Eng. 2016;2(10):1662–78.

    CAS  Google Scholar 

  63. 63.

    Wang Z, Abdulla R, Parker B, Samanipour R, Ghosh S, Kim K. A simple and high-resolution stereolithography-based 3D bioprinting system using visible light crosslinkable bioinks. Biofabrication. 2015;7(4):045009.

    PubMed  Google Scholar 

  64. 64.

    Christensen K, Xu C, Chai W, Zhang Z, Fu J, Huang Y. Freeform inkjet printing of cellular structures with bifurcations. Biotechnol Bioeng. 2015;112(5):1047–55.

    CAS  PubMed  Google Scholar 

  65. 65.

    Müller M, Becher J, Schnabelrauch M, Zenobi-Wong M. Nanostructured Pluronic hydrogels as bioinks for 3D bioprinting. Biofabrication. 2015;7(3):035006.

    PubMed  Google Scholar 

  66. 66.

    Ruan J-L, 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Radisic M, Park H, Shing H, Consi T, Schoen FJ, Langer R, 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(52):18129–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Maiullari F, Costantini M, Milan M, Pace V, Chirivì M, Maiullari S, et al. A multi-cellular 3D bioprinting approach for vascularized heart tissue engineering based on HUVECs and iPSC-derived cardiomyocytes. Sci Rep [Internet]. 2018 Dec [cited 2019 Feb 27];8(1). Available from:

  69. 69.

    •• Redd MA, Zeinstra N, Qin W, Wei W, Martinson A, Wang Y, et al. Patterned human microvascular grafts enable rapid vascularization and increase perfusion in infarcted rat hearts. Nat Commun. 2019;10(1):584. Current state-of-the-art showing vascular remodeling and integration of engineered microchannel networks.

    PubMed  PubMed Central  Google Scholar 

  70. 70.

    Zhang YS, Arneri A, Bersini S, Shin S-R, Zhu K, Goli-Malekabadi Z, et al. Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip. Biomaterials. 2016;110:45–59.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Miller JS, Stevens KR, Yang MT, Baker BM, Nguyen D-HT, Cohen DM, et al. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nat Mater. 2012;11(9):768–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Skylar-Scott MA, Gunasekaran S, Lewis JA. Laser-assisted direct ink writing of planar and 3D metal architectures. Proc Natl Acad Sci. 2016;113(22):6137–42.

    CAS  PubMed  Google Scholar 

  73. 73.

    Jang J, Park H-J, Kim S-W, Kim H, Park JY, Na SJ, et al. 3D printed complex tissue construct using stem cell-laden decellularized extracellular matrix bioinks for cardiac repair. Biomaterials. 2017;112:264–74.

    CAS  PubMed  Google Scholar 

  74. 74.

    Brandenberg N, Lutolf MP. In situ patterning of microfluidic networks in 3D cell-laden hydrogels. Adv Mater Deerfield Beach Fla. 2016;28(34):7450–6.

    CAS  Google Scholar 

  75. 75.

    Brutsaert DL. Cardiac endothelial-myocardial signaling: its role in cardiac growth, contractile performance, and rhythmicity. Physiol Rev. 2003;83(1):59–115.

    CAS  PubMed  Google Scholar 

  76. 76.

    Montgomery M, Zhang B, Radisic M. Cardiac tissue vascularization: from angiogenesis to microfluidic blood vessels. J Cardiovasc Pharmacol Ther. 2014;19(4):382–93.

    CAS  PubMed  Google Scholar 

  77. 77.

    Potter RF, Groom AC. Capillary diameter and geometry in cardiac and skeletal muscle studied by means of corrosion casts. Microvasc Res. 1983;25(1):68–84.

    CAS  PubMed  Google Scholar 

  78. 78.

    Levenberg S, Rouwkema J, Macdonald M, Garfein ES, Kohane DS, Darland DC, et al. Engineering vascularized skeletal muscle tissue. Nat Biotechnol. 2005;23(7):879–84.

    CAS  PubMed  Google Scholar 

  79. 79.

    Tremblay P-L, Hudon V, Berthod F, Germain L, Auger FA. Inosculation of tissue-engineered capillaries with the host’s vasculature in a reconstructed skin transplanted on mice. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2005;5(5):1002–10.

    Google Scholar 

  80. 80.

    Gulino D, Delachanal E, Concord E, Genoux Y, Morand B, Valiron MO, et al. Alteration of endothelial cell monolayer integrity triggers resynthesis of vascular endothelium cadherin. J Biol Chem. 1998;273(45):29786–93.

    CAS  PubMed  Google Scholar 

  81. 81.

    Schnaper HW, Kleinman HK. Regulation of cell function by extracellular matrix. Pediatr Nephrol Berl Ger. 1993;7(1):96–104.

    CAS  Google Scholar 

  82. 82.

    Baiguera S, Ribatti D. Endothelialization approaches for viable engineered tissues. Angiogenesis. 2013;16(1):1–14.

    CAS  PubMed  Google Scholar 

  83. 83.

    Perry L, Flugelman MY, Levenberg S. Elderly patient-derived endothelial cells for vascularization of engineered muscle. Mol Ther J Am Soc Gene Ther. 2017;25(4):935–48.

    CAS  Google Scholar 

  84. 84.

    Kurokawa YK, Yin RT, Shang MR, Shirure VS, Moya ML, George SC. Human induced pluripotent stem cell-derived endothelial cells for three-dimensional microphysiological systems. Tissue Eng Part C Methods. 2017;23(8):474–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Kurisaki A, Ito Y, Onuma Y, Intoh A, Asashima M. In vitro organogenesis using multipotent cells. Hum Cell. 2010;23(1):1–14.

    PubMed  Google Scholar 

  86. 86.

    Elcheva I, Brok-Volchanskaya V, Kumar A, Liu P, Lee J-H, Tong L, et al. Direct induction of haematoendothelial programs in human pluripotent stem cells by transcriptional regulators. Nat Commun. 2014;5:4372.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. 87.

    Chen X, Aledia AS, Ghajar CM, Griffith CK, Putnam AJ, Hughes CCW, et al. Prevascularization of a fibrin-based tissue construct accelerates the formation of functional anastomosis with host vasculature. Tissue Eng Part A. 2009;15(6):1363–71.

    CAS  PubMed  Google Scholar 

  88. 88.

    Hughes CCW. Endothelial-stromal interactions in angiogenesis. Curr Opin Hematol. 2008;15(3):204–9.

    PubMed  PubMed Central  Google Scholar 

  89. 89.

    Liu S, Zhang H, Zhang X, Lu W, Huang X, Xie H, et al. Synergistic angiogenesis promoting effects of extracellular matrix scaffolds and adipose-derived stem cells during wound repair. Tissue Eng Part A. 2011;17(5–6):725–39.

    CAS  PubMed  Google Scholar 

  90. 90.

    D’Amore PA. Capillary growth: a two-cell system. Semin Cancer Biol. 1992;3(2):49–56.

    PubMed  Google Scholar 

  91. 91.

    Ghajar CM, Chen X, Harris JW, Suresh V, Hughes CCW, Jeon NL, et al. The effect of matrix density on the regulation of 3-D capillary morphogenesis. Biophys J. 2008;94(5):1930–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Velazquez OC, Snyder R, Liu Z-J, Fairman RM, Herlyn M. Fibroblast-dependent differentiation of human microvascular endothelial cells into capillary-like 3-dimensional networks. FASEB J Off Publ Fed Am Soc Exp Biol. 2002;16(10):1316–8.

    CAS  Google Scholar 

  93. 93.

    Folkman J, D’Amore PA. Blood vessel formation: what is its molecular basis? Cell. 1996;87(7):1153–5.

    CAS  PubMed  Google Scholar 

  94. 94.

    Darland DC, D’Amore PA. Blood vessel maturation: vascular development comes of age. J Clin Invest. 1999;103(2):157–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. 95.

    Darland DC, D’Amore PA. Cell-cell interactions in vascular development. Curr Top Dev Biol. 2001;52:107–49.

    CAS  PubMed  Google Scholar 

  96. 96.

    Arslan-Yildiz A, El Assal R, Chen P, Guven S, Inci F, Demirci U. Towards artificial tissue models: past, present, and future of 3D bioprinting. Biofabrication. 2016;8(1):014103.

    PubMed  Google Scholar 

Download references


We thank Mark Skylar-Scott, PhD (Wyss Institute for Biologically Inspired Engineering, Harvard University) for his comments and edits on the manuscript.


Funding for this research was provided by the German Research Foundation/DFG (PU 690/1-1) (N.P.), the NIH Office of Director’s Pioneer Award LM012179-03, the American Heart Association Established Investigator Award 17EIA33410923, the Stanford Cardiovascular Institute, the Hoffmann and Schroepfer Foundation, and the Stanford Division of Cardiovascular Medicine, Department of Medicine (S.M.W). The authors declare no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Author information



Corresponding author

Correspondence to Sean M. Wu.

Ethics declarations

Conflict of Interest

Nazan Puluca, Soah Lee, Stephanie Doppler, Andrea Münsterer, Martina Dreßen, Markus Krane, and Sean M. Wu declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Regenerative Medicine

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Puluca, N., Lee, S., Doppler, S. et al. Bioprinting Approaches to Engineering Vascularized 3D Cardiac Tissues. Curr Cardiol Rep 21, 90 (2019).

Download citation


  • 3D printing
  • Cardiac engineered tissue
  • Vascularization
  • Bioprinting
  • Cardiovascular tissue
  • Cardiomyocyte