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Engineering Functional Cardiac Tissues for Regenerative Medicine Applications

  • Regenerative Medicine (SM Wu, Section Editor)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Tissue engineering has expanded into a highly versatile manufacturing landscape that holds great promise for advancing cardiovascular regenerative medicine. In this review, we provide a summary of the current state-of-the-art bioengineering technologies used to create functional cardiac tissues for a variety of applications in vitro and in vivo.

Recent Findings

Studies over the past few years have made a strong case that tissue engineering is one of the major driving forces behind the accelerating fields of patient-specific regenerative medicine, precision medicine, compound screening, and disease modeling. To date, a variety of approaches have been used to bioengineer functional cardiac constructs, including biomaterial-based, cell-based, and hybrid (using cells and biomaterials) approaches. While some major progress has been made using cellular approaches, with multiple ongoing clinical trials, cell-free cardiac tissue engineering approaches have also accomplished multiple breakthroughs, although drawbacks remain.

Summary

This review summarizes the most promising methods that have been employed to generate cardiovascular tissue constructs for basic science or clinical applications. Further, we outline the strengths and challenges that are inherent to this field as a whole and for each highlighted technology.

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References

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

  1. Serpooshan V, Zhao M, Metzler SA, Wei K, Shah PB, Wang A, et al. Use of bio-mimetic three-dimensional technology in therapeutics for heart disease. Bioengineered. 2014;5(3):193–7.

    PubMed  PubMed Central  Google Scholar 

  2. Doppler SA, Deutsch MA, Serpooshan V, Li G, Dzilic E, Lange R, et al. Mammalian heart regeneration: the race to the finish line. Circ Res. 2017;120(4):630–2.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Duan B. State-of-the-art review of 3D bioprinting for cardiovascular tissue engineering. Ann Biomed Eng. 2017;45(1):195–209.

    PubMed  Google Scholar 

  4. Ahadian S, Khademhosseini A. Smart scaffolds in tissue regeneration. Regen Biomater. 2018;5(3):125–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Ashammakhi N, et al. Advances and future perspectives in 4D bioprinting. Biotechnol J. 2018;13(12):e1800148.

    PubMed  PubMed Central  Google Scholar 

  6. 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 

  7. Tomov ML, Olmsted ZT, Paluh JL. The human embryoid body cystic core exhibits architectural complexity revealed by use of high throughput polymer microarrays. Macromol Biosci. 2015;15(7):892–900.

    CAS  PubMed  Google Scholar 

  8. Tomov ML, Tsompana M, Olmsted ZT, Buck M, Paluh JL. Human embryoid body transcriptomes reveal maturation differences influenced by size and formation in custom microarrays. J Nanosci Nanotechnol. 2016;16(9):8978–88.

    CAS  Google Scholar 

  9. Hu JB, Tomov ML, Buikema JW, Chen C, Mahmoudi M, Wu SM, et al. Cardiovascular tissue bioprinting: physical and chemical processes. Appl Phys Rev. 2018;5(4):041106.

    PubMed  PubMed Central  Google Scholar 

  10. Huang NF, Serpooshan V, Morris VB, Sayed N, Pardon G, Abilez OJ, et al. Big bottlenecks in cardiovascular tissue engineering. Commun Biol. 2018;1(1):199.

    PubMed  PubMed Central  Google Scholar 

  11. Lee S, Serpooshan V, Tong X, Venkatraman S, Lee M, Lee J, et al. Contractile force generation by 3D hiPSC-derived cardiac tissues is enhanced by rapid establishment of cellular interconnection in matrix with muscle-mimicking stiffness. Biomaterials. 2017;131:111–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Bitar KN, Zakhem E. Design strategies of biodegradable scaffolds for tissue regeneration. Biomed Eng Comput Biol. 2014;6:13–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Arnal-Pastor M, et al. Biomaterials for cardiac tissue engineering. Regen Med Tissue Eng. 2013:275–323.

  14. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, et al. Bone marrow cells regenerate infarcted myocardium. Nature. 2001;410(6829):701–5.

    CAS  PubMed  Google Scholar 

  15. Kulandavelu S, Balkan W, Hare JM. Next-generation stem cell therapy: genetically modified mesenchymal stem cells for cardiac repair: editorial to: “Mesenchymal Stem Cells with eNOS Over-Expression Enhance Cardiac Repair in Rats with Myocardial Infarction” by Leilei Chen et al. Cardiovasc Drugs Ther. 2017;31(1):5–7.

    PubMed  Google Scholar 

  16. Thakker R, Yang P. Mesenchymal stem cell therapy for cardiac repair. Curr Treat Options Cardiovasc Med. 2014;16(7):323.

    PubMed  PubMed Central  Google Scholar 

  17. Zwi-Dantsis L, Gepstein L. Induced pluripotent stem cells for cardiac repair. Cell Mol Life Sci. 2012;69(19):3285–99.

    CAS  PubMed  Google Scholar 

  18. Lalit PA, Hei DJ, Raval AN, Kamp TJ. Induced pluripotent stem cells for post-myocardial infarction repair: remarkable opportunities and challenges. Circ Res. 2014;114(8):1328–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Leong YY, Ng WH, Ellison-Hughes GM, Tan JJ. Cardiac stem cells for myocardial regeneration: they are not alone. Front Cardiovasc Med. 2017;4(4):47.

    PubMed  PubMed Central  Google Scholar 

  20. Serpooshan V, Liu YH, Buikema JW, Galdos FX, Chirikian O, Paige S, et al. Nkx2.5+ cardiomyoblasts contribute to cardiomyogenesis in the neonatal heart. Sci Rep. 2017;7(1):12590.

    PubMed  PubMed Central  Google Scholar 

  21. Taylor DA, Atkins BZ, Hungspreugs P, Jones TR, Reedy MC, Hutcheson KA, et al. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med. 1998;4(8):929–33.

    CAS  PubMed  Google Scholar 

  22. Chistiakov DA, Orekhov AN, Bobryshev YV. The role of cardiac fibroblasts in post-myocardial heart tissue repair. Exp Mol Pathol. 2016;101(2):231–40.

    CAS  PubMed  Google Scholar 

  23. Yuan P, Ma X. Endothelial cells facilitate cell-based cardiac repair: progress and challenge. Curr Stem Cell Res Ther. 2014;9(5):415–23.

    CAS  PubMed  Google Scholar 

  24. Dunn KK, Palecek SP. Engineering scalable manufacturing of high-quality stem cell-derived cardiomyocytes for cardiac tissue repair. Front Med. 2018;5:110.

    Google Scholar 

  25. Masoudpour H, Laflamme MA. Cardiac repair with pluripotent stem cell-derived cardiomyocytes: proof of concept but new challenges. J Thorac Cardiovasc Surg. 2017;154(3):945–8.

    PubMed  Google Scholar 

  26. Lundy SD, Gantz JA, Pagan CM, Filice D, Laflamme MA. Pluripotent stem cell derived cardiomyocytes for cardiac repair. Curr Treat Options Cardiovasc Med. 2014;16(7):319.

    PubMed  PubMed Central  Google Scholar 

  27. Zhang H, Chen H, Wang W, Wei Y, Hu S. Cell survival and redistribution after transplantation into damaged myocardium. J Cell Mol Med. 2010;14(5):1078–82.

    PubMed  PubMed Central  Google Scholar 

  28. Baldari S, di Rocco G, Piccoli M, Pozzobon M, Muraca M, Toietta G. Challenges and strategies for improving the regenerative effects of mesenchymal stromal cell-based therapies. Int J Mol Sci. 2017;18(10).

    PubMed Central  Google Scholar 

  29. Lee JK, Link JM, Hu JCY, Athanasiou KA. The self-assembling process and applications in tissue engineering. Cold Spring Harb Perspect Med. 2017;7(11).

    PubMed  PubMed Central  Google Scholar 

  30. Moldovan NI. Progress in scaffold-free bioprinting for cardiovascular medicine. J Cell Mol Med. 2018;22(6):2964–9.

    PubMed  PubMed Central  Google Scholar 

  31. Aguilar IN, Smith LJ, Olivos DJ III, Chu TMG, Kacena MA, Wagner DR. Scaffold-free bioprinting of mesenchymal stem cells with the regenova printer: optimization of printing parameters. Bioprinting. 2019;15:e00048.

    PubMed  PubMed Central  Google Scholar 

  32. Rouwkema J, et al. Supply of nutrients to cells in engineered tissues. Biotechnol Genet Eng Rev. 2010;26:163–78.

    CAS  PubMed  Google Scholar 

  33. Norotte C, Marga FS, Niklason LE, Forgacs G. Scaffold-free vascular tissue engineering using bioprinting. Biomaterials. 2009;30(30):5910–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Yu Y, Moncal KK, Li J, Peng W, Rivero I, Martin JA, et al. Three-dimensional bioprinting using self-assembling scalable scaffold-free “tissue strands” as a new bioink. Sci Rep. 2016;6:28714.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Noguchi R, Nakayama K, Itoh M, Kamohara K, Furukawa K, Oyama JI, et al. Development of a three-dimensional pre-vascularized scaffold-free contractile cardiac patch for treating heart disease. J Heart Lung Transplant. 2016;35(1):137–45.

    PubMed  Google Scholar 

  36. Esmaeili Pourfarhangi K, Mashayekhan S, Asl SG, Hajebrahimi Z. Construction of scaffolds composed of acellular cardiac extracellular matrix for myocardial tissue engineering. Biologicals. 2018;53:10–8.

    CAS  PubMed  Google Scholar 

  37. Courtman DW, Pereira CA, Kashef V, McComb D, Lee JM, Wilson GJ. Development of a pericardial acellular matrix biomaterial: biochemical and mechanical effects of cell extraction. J Biomed Mater Res. 1994;28(6):655–66.

    CAS  PubMed  Google Scholar 

  38. Burdick JA, et al. Acellular biomaterials: an evolving alternative to cell-based therapies. Sci Transl Med. 2013;5(176):176ps4.

    PubMed  PubMed Central  Google Scholar 

  39. da Silveira JS, Scansen BA, Wassenaar PA, Raterman B, Eleswarpu C, Jin N, et al. Quantification of myocardial stiffness using magnetic resonance elastography in right ventricular hypertrophy: initial feasibility in dogs. Magn Reson Imaging. 2016;34(1):26–34.

    PubMed  Google Scholar 

  40. Lee S, et al. Hydrogel degradation modulates human iPSC-derived cardiomyocyte fates in 3D. Front Bioeng Biotechnol.

  41. • Wei K, et al. Epicardial FSTL1 reconstitution regenerates the adult mammalian heart. Nature. 2015;525(7570):479–85 Reporting a novel effect of an embryonic epicardial patch, loaded with a paracrine cardiokine (FSTL1), on stimulating adult cardiomyocytes to re-enter cell cylce and proliferate.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Galvez-Monton C, et al. Cardiac Tissue Engineering and the Bioartificial Heart. Rev Esp Cardiol. 2013;66(5):391–9.

    PubMed  Google Scholar 

  43. Gershlak JR, Hernandez S, Fontana G, Perreault LR, Hansen KJ, Larson SA, et al. Crossing kingdoms: using decellularized plants as perfusable tissue engineering scaffolds. Biomaterials. 2017;125:13–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Serpooshan V, Chen P, Wu H, Lee S, Sharma A, Hu DA, et al. Bioacoustic-enabled patterning of human iPSC-derived cardiomyocytes into 3D cardiac tissue. Biomaterials. 2017;131:47–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Momtahan N, Poornejad N, Struk JA, Castleton AA, Herrod BJ, Vance BR, et al. Automation of pressure control improves whole porcine heart decellularization. Tissue Eng Part C Methods. 2015;21(11):1148–61.

    CAS  PubMed  Google Scholar 

  46. Dar A, Shachar M, Leor J, Cohen S. Optimization of cardiac cell seeding and distribution in 3D porous alginate scaffolds. Biotechnol Bioeng. 2002;80(3):305–12.

    CAS  PubMed  Google Scholar 

  47. Sapir Y, Kryukov O, Cohen S. Integration of multiple cell-matrix interactions into alginate scaffolds for promoting cardiac tissue regeneration. Biomaterials. 2011;32(7):1838–47.

    CAS  PubMed  Google Scholar 

  48. Khan K, Gasbarrino K, Mahmoud I, Makhoul G, Yu B, Dufresne L, et al. Bioactive scaffolds in stem-cell-based therapies for cardiac repair: protocol for a meta-analysis of randomized controlled preclinical trials in animal myocardial infarction models. Syst Rev. 2018;7(1):225.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Chen QZ, Harding SE, Ali NN, Lyon AR, Boccaccini AR. Biomaterials in cardiac tissue engineering: ten years of research survey. Mater Sci Eng Rep. 2008;59(1–6):1–37.

    Google Scholar 

  50. Sun Y, Han X, Wang X, Zhu B, Li B, Chen Z, et al. Sustained release of IGF-1 by 3D mesoporous scaffolds promoting cardiac stem cell migration and proliferation. Cell Physiol Biochem. 2018;49(6):2358–70.

    CAS  PubMed  Google Scholar 

  51. Leor J, Amsalem Y, Cohen S. Cells, scaffolds, and molecules for myocardial tissue engineering. Pharmacol Ther. 2005;105(2):151–63.

    CAS  PubMed  Google Scholar 

  52. Huyer LD, Montgomery M, Zhao Y, Xiao Y, Conant G, Korolj A, et al. Biomaterial based cardiac tissue engineering and its applications. Biomed Mater. 2015;10(3):034004.

    PubMed  PubMed Central  Google Scholar 

  53. Keane TJ, Badylak SF. Biomaterials for tissue engineering applications. Semin Pediatr Surg. 2014;23(3):112–8.

    PubMed  Google Scholar 

  54. Di Felice V, et al. Silk fibroin scaffolds enhance cell commitment of adult rat cardiac progenitor cells. J Tissue Eng Regen Med. 2015;9(11):E51–64.

    PubMed  Google Scholar 

  55. Izadifar M, Chapman D, Babyn P, Chen X, Kelly ME. UV-assisted 3D bioprinting of nanoreinforced hybrid cardiac patch for myocardial tissue engineering. Tissue Eng Part C Methods. 2018;24(2):74–88.

    CAS  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  57. Wang Z, Lee SJ, Cheng HJ, Yoo JJ, Atala A. 3D bioprinted functional and contractile cardiac tissue constructs. Acta Biomater. 2018;70:48–56.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. •• Kang HW, et al. A 3D bioprinting system to produce human-scale tissue constructs with structural integrity. Nat Biotechnol. 2016;34(3):312–9 Demonstrated capabilities of integrated tissue–organ printers by fabricating mandible and calvarial bone, cartilage and skeletal muscle.

    CAS  PubMed  Google Scholar 

  59. •• Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nat Biotechnol. 2014;32(8):773–85 A seminal work reviewing the application of 3D bioprinting to tissue and organ engineering.

    CAS  PubMed  Google Scholar 

  60. Gungor-Ozkerim PS, Inci I, Zhang YS, Khademhosseini A, Dokmeci MR. Bioinks for 3D bioprinting: an overview. Biomater Sci. 2018;6(5):915–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Gopinathan J, Noh I. Recent trends in bioinks for 3D printing. Biomater Res. 2018;22:11.

    PubMed  PubMed Central  Google Scholar 

  62. Li X, Liu L, Zhang X, Xu T. Research and development of 3D printed vasculature constructs. Biofabrication. 2018;10(3):032002.

    PubMed  Google Scholar 

  63. Tijore A, Irvine SA, Sarig U, Mhaisalkar P, Baisane V, Venkatraman S. Contact guidance for cardiac tissue engineering using 3D bioprinted gelatin patterned hydrogel. Biofabrication. 2018;10(2).

    PubMed  Google Scholar 

  64. Hu JB, et al. Bioengineering of vascular myocardial tissue; a 3D bioprinting approach. Tissue Eng A. 2017;23:S158–9.

    Google Scholar 

  65. Lee S, et al. 3D bioprinted functional and contractile cardiac tissue constructs. Tissue Eng A. 2017;23:S96–6.

  66. Zhang Y, Yu Y, Akkouch A, Dababneh A, Dolati F, Ozbolat IT. In vitro study of directly bioprinted perfusable vasculature conduits. Biomater Sci. 2015;3(1):134–43.

    CAS  PubMed  Google Scholar 

  67. Ho CM, et al. 3D printed polycaprolactone carbon nanotube composite scaffolds for cardiac tissue engineering. Macromol Biosci. 2017;17(4).

    Google Scholar 

  68. Jang J, Park HJ, Kim SW, 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 

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

    CAS  PubMed  Google Scholar 

  70. Ma X, Dewan S, Liu J, Tang M, Miller KL, Yu C, et al. 3D printed micro-scale force gauge arrays to improve human cardiac tissue maturation and enable high throughput drug testing. Acta Biomater. 2018.

  71. Pattanaik S, Arbra C, Bainbridge H, Dennis SG, Fann SA, Yost MJ. Vascular tissue engineering using scaffold-free prevascular endothelial-fibroblast constructs. Biores Open Access. 2019;8(1):1–15.

    PubMed  PubMed Central  Google Scholar 

  72. Jang J. 3D bioprinting and in vitro cardiovascular tissue modeling. Bioengineering (Basel). 2017;4(3).

    PubMed Central  Google Scholar 

  73. Kim YK, Park JA, Yoon WH, Kim J, Jung S. Drop-on-demand inkjet-based cell printing with 30-mum nozzle diameter for cell-level accuracy. Biomicrofluidics. 2016;10(6):064110.

    PubMed  PubMed Central  Google Scholar 

  74. Hinton TJ, Jallerat Q, Palchesko RN, Park JH, Grodzicki MS, Shue HJ, et al. Three-dimensional printing of complex biological structures by freeform reversible embedding of suspended hydrogels. Sci Adv. 2015;1(9):e1500758.

    PubMed  PubMed Central  Google Scholar 

  75. Tan Y, Kong CW, Chen S, Cheng SH, Li RA, Sun D. Probing the mechanobiological properties of human embryonic stem cells in cardiac differentiation by optical tweezers. J Biomech. 2012;45(1):123–8.

    PubMed  Google Scholar 

  76. Jing P, Liu Y, Keeler EG, Cruz NM, Freedman BS, Lin LY. Optical tweezers system for live stem cell organization at the single-cell level. Biomed Opt Express. 2018;9(2):771–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. 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 

  78. Gaebel R, Ma N, Liu J, Guan J, Koch L, Klopsch C, et al. Patterning human stem cells and endothelial cells with laser printing for cardiac regeneration. Biomaterials. 2011;32(35):9218–30.

    CAS  PubMed  Google Scholar 

  79. 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 

  80. Tomov ML, Olmsted ZT, Dogan H, Gongorurler E, Tsompana M, Otu HH, et al. Distinct and shared determinants of cardiomyocyte contractility in multi-lineage competent ethnically diverse human iPSCs. Sci Rep. 2016;6:37637.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Dergilev K, et al. C-kit cardiac progenitor cell based cell sheet improves vascularization and attenuates cardiac remodeling following myocardial infarction in rats. Biomed Res Int. 2018;2018:3536854.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Furuta A, Miyoshi S, Itabashi Y, Shimizu T, Kira S, Hayakawa K, et al. Pulsatile cardiac tissue grafts using a novel three-dimensional cell sheet manipulation technique functionally integrates with the host heart, in vivo. Circ Res. 2006;98(5):705–12.

    CAS  PubMed  Google Scholar 

  83. Kamata S, Miyagawa S, Fukushima S, Nakatani S, Kawamoto A, Saito A, et al. Improvement of cardiac stem cell sheet therapy for chronic ischemic injury by adding endothelial progenitor cell transplantation: analysis of layer-specific regional cardiac function. Cell Transplant. 2014;23(10):1305–19.

    PubMed  Google Scholar 

  84. Sekiya S, Shimizu T, Yamato M, Kikuchi A, Okano T. Bioengineered cardiac cell sheet grafts have intrinsic angiogenic potential. Biochem Biophys Res Commun. 2006;341(2):573–82.

    CAS  PubMed  Google Scholar 

  85. Shimizu T, Yamato M, Isoi Y, Akutsu T, Setomaru T, Abe K, et al. Fabrication of pulsatile cardiac tissue grafts using a novel 3-dimensional cell sheet manipulation technique and temperature-responsive cell culture surfaces. Circ Res. 2002;90(3):e40.

    CAS  PubMed  Google Scholar 

  86. Harada S, Nakamura Y, Shiraya S, Fujiwara Y, Kishimoto Y, Onohara T, et al. Smooth muscle cell sheet transplantation preserve cardiac function and minimize cardiac remodeling in a rat myocardial infarction model. J Cardiothorac Surg. 2016;11(1):131.

    PubMed  PubMed Central  Google Scholar 

  87. Zakharova L, Mastroeni D, Mutlu N, Molina M, Goldman S, Diethrich E, et al. Transplantation of cardiac progenitor cell sheet onto infarcted heart promotes cardiogenesis and improves function. Cardiovasc Res. 2010;87(1):40–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Masuda S, Shimizu T. Three-dimensional cardiac tissue fabrication based on cell sheet technology. Adv Drug Deliv Rev. 2016;96:103–9.

    CAS  PubMed  Google Scholar 

  89. Sakaguchi K, Shimizu T, Okano T. Construction of three-dimensional vascularized cardiac tissue with cell sheet engineering. J Control Release. 2015;205:83–8.

    CAS  PubMed  Google Scholar 

  90. Banerjee MN, Bolli R, Hare JM. Clinical studies of cell therapy in cardiovascular medicine: recent developments and future directions. Circ Res. 2018;123(2):266–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Pena B, et al. Injectable hydrogels for cardiac tissue engineering. Macromol Biosci. 2018;18(6):e1800079.

    PubMed  PubMed Central  Google Scholar 

  92. Hasan A, Khattab A, Islam MA, Hweij KA, Zeitouny J, Waters R, et al. Injectable hydrogels for cardiac tissue repair after myocardial infarction. Adv Sci (Weinh). 2015;2(11):1500122.

    Google Scholar 

  93. Lee KY, Mooney DJ. Hydrogels for tissue engineering. Chem Rev. 2001;101(7):1869–79.

    CAS  PubMed  Google Scholar 

  94. Park H, Kang SW, Kim BS, Mooney DJ, Lee KY. Shear-reversibly crosslinked alginate hydrogels for tissue engineering. Macromol Biosci. 2009;9(9):895–901.

    CAS  PubMed  Google Scholar 

  95. Reis LA, Chiu LLY, Feric N, Fu L, Radisic M. Biomaterials in myocardial tissue engineering. J Tissue Eng Regen Med. 2016;10(1):11–28.

    CAS  PubMed  Google Scholar 

  96. Muller P, Lemcke H, David R. Stem cell therapy in heart diseases—cell types, mechanisms and improvement strategies. Cell Physiol Biochem. 2018;48(6):2607–55.

    PubMed  Google Scholar 

  97. Golpanian S, Wolf A, Hatzistergos KE, Hare JM. Rebuilding the damaged heart: mesenchymal stem cells, cell-based therapy, and engineered heart tissue. Physiol Rev. 2016;96(3):1127–68.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, et al. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med. 2005;11(4):367–8.

    CAS  PubMed  Google Scholar 

  99. Hodgkinson CP, Bareja A, Gomez JA, Dzau VJ. Emerging concepts in paracrine mechanisms in regenerative cardiovascular medicine and biology. Circ Res. 2016;118(1):95–107.

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Kanda P, Davis DR. Cellular mechanisms underlying cardiac engraftment of stem cells. Expert Opin Biol Ther. 2017;17(9):1127–43.

    CAS  PubMed  Google Scholar 

  101. Li X, et al. Improving cell engraftment in cardiac stem cell therapy. Stem Cells Int. 2016;2016:7168797.

    PubMed  Google Scholar 

  102. Hatzistergos KE, Quevedo H, Oskouei BN, Hu Q, Feigenbaum GS, Margitich IS, et al. Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circ Res. 2010;107(7):913–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Zhang S, Wang D, Estrov Z, Raj S, Willerson JT, Yeh ETH. Both cell fusion and transdifferentiation account for the transformation of human peripheral blood CD34-positive cells into cardiomyocytes in vivo. Circulation. 2004;110(25):3803–7.

    PubMed  Google Scholar 

  104. Mathison M, Rosengart TK. Heart regeneration: the endothelial cell comes first. J Thorac Cardiovasc Surg. 2018;155(3):1128–9.

    PubMed  Google Scholar 

  105. Domenech M, Polo-Corrales L, Ramirez-Vick JE, Freytes DO. Tissue engineering strategies for myocardial regeneration: acellular versus cellular scaffolds? Tissue Eng Part B Rev. 2016;22(6):438–58.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Pal A, Vernon BL, Nikkhah M. Therapeutic neovascularization promoted by injectable hydrogels. Bioact Mater. 2018;3(4):389–400.

    PubMed  PubMed Central  Google Scholar 

  107. Radhakrishnan J, Krishnan UM, Sethuraman S. Hydrogel based injectable scaffolds for cardiac tissue regeneration. Biotechnol Adv. 2014;32(2):449–61.

    CAS  PubMed  Google Scholar 

  108. Mahmoudi M, Zhao M, Matsuura Y, Laurent S, Yang PC, Bernstein D, et al. Infection-resistant MRI-visible scaffolds for tissue engineering applications. Bioimpacts. 2016;6(2):111–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Serpooshan V, Mahmoudi M, Zhao M, Wei K, Sivanesan S, Motamedchaboki K, et al. Protein corona influences cell-biomaterial interactions in nanostructured tissue engineering scaffolds. Adv Funct Mater. 2015;25(28):4379–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Serpooshan V, Zhao M, Metzler SA, Wei K, Shah PB, Wang A, et al. The effect of bioengineered acellular collagen patch on cardiac remodeling and ventricular function post myocardial infarction. Biomaterials. 2013;34(36):9048–55.

    CAS  PubMed  Google Scholar 

  111. Vunjak Novakovic G, Eschenhagen T, Mummery C. Myocardial tissue engineering: in vitro models. Cold Spring Harb Perspect Med. 2014;4(3).

    PubMed  PubMed Central  Google Scholar 

  112. Serpooshan V, Ruiz-Lozano P. Ultra-rapid manufacturing of engineered epicardial substitute to regenerate cardiac tissue following acute ischemic injury. Methods Mol Biol. 2014;1210:239–48.

    CAS  PubMed  Google Scholar 

  113. Nelson CM, VanDuijn MM, Inman JL, Fletcher DA, Bissell MJ. Tissue geometry determines sites of mammary branching morphogenesis in organotypic cultures. Science. 2006;314(5797):298–300.

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Lee K, Silva EA, Mooney DJ. Growth factor delivery-based tissue engineering: general approaches and a review of recent developments. J R Soc Interface. 2011;8(55):153–70.

    CAS  PubMed  Google Scholar 

  115. Miller JS, Stevens KR, Yang MT, Baker BM, Nguyen DHT, Cohen DM, et al. Rapid casting of patterned vascular networks for perfusable engineered 3D tissues. Nat Mater. 2012;11(9):768–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Miller JS, Stevens KR, Yang MT, Baker BM, Nguyen DHT, 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 

  117. Jayakumar MK, Idris NM, Zhang Y. Remote activation of biomolecules in deep tissues using near-infrared-to-UV upconversion nanotransducers. Proc Natl Acad Sci U S A. 2012;109(22):8483–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Guyette JP, Gilpin SE, Charest JM, Tapias LF, Ren X, Ott HC. Perfusion decellularization of whole organs. Nat Protoc. 2014;9(6):1451–68.

    CAS  PubMed  Google Scholar 

  119. Gilbert TW. Strategies for tissue and organ decellularization. J Cell Biochem. 2012;113(7):2217–22.

    CAS  PubMed  Google Scholar 

  120. Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat Med. 2008;14(2):213–21.

    CAS  PubMed  Google Scholar 

  121. Gerli MFM, Guyette JP, Evangelista-Leite D, Ghoshhajra BB, Ott HC. Perfusion decellularization of a human limb: a novel platform for composite tissue engineering and reconstructive surgery. PLoS One. 2018;13(1):e0191497.

    PubMed  PubMed Central  Google Scholar 

  122. Ng SL, et al. Lineage restricted progenitors for the repopulation of decellularized heart. Biomaterials. 2011;32(30):7571–80.

    CAS  PubMed  Google Scholar 

  123. Seetapun D, Ross JJ. Eliminating the organ transplant waiting list: the future with perfusion decellularized organs. Surgery. 2017;161(6):1474–8.

    PubMed  Google Scholar 

  124. Cimetta E, Pizzato S, Bollini S, Serena E, de Coppi P, Elvassore N. Production of arrays of cardiac and skeletal muscle myofibers by micropatterning techniques on a soft substrate. Biomed Microdevices. 2009;11(2):389–400.

    CAS  PubMed  Google Scholar 

  125. Kim JJ, Hou L, Huang NF. Vascularization of three-dimensional engineered tissues for regenerative medicine applications. Acta Biomater. 2016;41:17–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Lee BW, Liu B, Pluchinsky A, Kim N, Eng G, Vunjak-Novakovic G. Modular assembly approach to engineer geometrically precise cardiovascular tissue. Adv Healthc Mater. 2016;5(8):900–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Salick MR, Napiwocki BN, Sha J, Knight GT, Chindhy SA, Kamp TJ, et al. Micropattern width dependent sarcomere development in human ESC-derived cardiomyocytes. Biomaterials. 2014;35(15):4454–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Pacharra S, et al. Surface patterning of a novel PEG-functionalized poly-l-lactide polymer to improve its biocompatibility: applications to bioresorbable vascular stents. J Biomed Mater Res B Appl Biomater. 2018.

  129. Yamaguchi M, Ikeda K, Suzuki M, Kiyohara A, Kudoh SN, Shimizu K, et al. Cell patterning using a template of microstructured organosilane layer fabricated by vacuum ultraviolet light lithography. Langmuir. 2011;27(20):12521–32.

    CAS  PubMed  Google Scholar 

  130. Atmanli A, Hu D, Domian IJ. Molecular etching: a novel methodology for the generation of complex micropatterned growth surfaces for human cellular assays. Adv Healthc Mater. 2014;3(11):1759–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Sugiura S, Cha JM, Yanagawa F, Zorlutuna P, Bae H, Khademhosseini A. Dynamic three-dimensional micropatterned cell co-cultures within photocurable and chemically degradable hydrogels. J Tissue Eng Regen Med. 2016;10(8):690–9.

    CAS  PubMed  Google Scholar 

  132. Yu H, Tay CY, Pal M, Leong WS, Li H, Li H, et al. A bio-inspired platform to modulate myogenic differentiation of human mesenchymal stem cells through focal adhesion regulation. Adv Healthc Mater. 2013;2(3):442–9.

    CAS  PubMed  Google Scholar 

  133. Guillemette MD, Park H, Hsiao JC, Jain SR, Larson BL, Langer R, et al. Combined technologies for microfabricating elastomeric cardiac tissue engineering scaffolds. Macromol Biosci. 2010;10(11):1330–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  134. Badie N, Bursac N. Novel micropatterned cardiac cell cultures with realistic ventricular microstructure. Biophys J. 2009;96(9):3873–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Entcheva E, Bien H. Acoustic micromachining of three-dimensional surfaces for biological applications. Lab Chip. 2005;5(2):179–83.

    CAS  PubMed  Google Scholar 

  136. Zhu Y, et al. Tissue engineering of 3D organotypic microtissues by acoustic assembly. Methods Mol Biol. 2017.

  137. Tian L, Martin N, Bassindale PG, Patil AJ, Li M, Barnes A, et al. Spontaneous assembly of chemically encoded two-dimensional coacervate droplet arrays by acoustic wave patterning. Nat Commun. 2016;7:13068.

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Senthamizhan A, Balusamy B, Uyar T. Electrospinning: a versatile processing technology for producing nanofibrous materials for biomedical and tissue-engineering applications. In: Electrospun materials for tissue engineering and biomedical applications: research, design and commercialization; 2017. p. 3–41.

    Google Scholar 

  139. Xie J, Wang CH. Encapsulation of proteins in biodegradable polymeric microparticles using electrospray in the Taylor cone-jet mode. Biotechnol Bioeng. 2007;97(5):1278–90.

    CAS  PubMed  Google Scholar 

  140. Kitsara M, Agbulut O, Kontziampasis D, Chen Y, Menasché P. Fibers for hearts: a critical review on electrospinning for cardiac tissue engineering. Acta Biomater. 2017;48:20–40.

    CAS  PubMed  Google Scholar 

  141. Senel Ayaz HG, et al. Textile-templated electrospun anisotropic scaffolds for regenerative cardiac tissue engineering. Biomaterials. 2014;35(30):8540–52.

    CAS  PubMed  Google Scholar 

  142. Prabhakaran MP, Nair AS, Kai D, Ramakrishna S. Electrospun composite scaffolds containing poly(octanediol-co-citrate) for cardiac tissue engineering. Biopolymers. 2012;97(7):529–38.

    CAS  PubMed  Google Scholar 

  143. Kai D, Prabhakaran MP, Jin G, Ramakrishna S. Guided orientation of cardiomyocytes on electrospun aligned nanofibers for cardiac tissue engineering. J Biomed Mater Res B Appl Biomater. 2011;98b(2):379–86.

    CAS  Google Scholar 

  144. Joanne P, Kitsara M, Boitard SE, Naemetalla H, Vanneaux V, Pernot M, et al. Nanofibrous clinical-grade collagen scaffolds seeded with human cardiomyocytes induces cardiac remodeling in dilated cardiomyopathy. Biomaterials. 2016;80:157–68.

    CAS  PubMed  Google Scholar 

  145. Ishii O, Shin M, Sueda T, Vacanti JP. In vitro tissue engineering of a cardiac graft using a degradable scaffold with an extracellular matrix-like topography. J Thorac Cardiovasc Surg. 2005;130(5):1358–63.

    PubMed  Google Scholar 

  146. Hekmati AH, Norouzi M. 12—electrospun scaffolds for cardiac tissue engineering. In: Uyar T, Kny E, editors. Electrospun materials for tissue engineering and biomedical applications: Woodhead Publishing; 2017. p. 289–97.

  147. Kitsara M, et al. Heart on a chip: micro-nanofabrication and microfluidics steering the future of cardiac tissue engineering. Microelectron Eng. 2019;203:44–62.

    Google Scholar 

  148. Ronaldson-Bouchard K, Vunjak-Novakovic G. Organs-on-a-chip: a fast track for engineered human tissues in drug development. Cell Stem Cell. 2018;22(3):310–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Grabowski H. Are the economics of pharmaceutical research and development changing?: productivity, patents and political pressures. Pharmacoeconomics. 2004;22(2 Suppl 2):15–24.

    PubMed  Google Scholar 

  150. Zhang YS, Arneri A, Bersini S, Shin SR, 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 

  151. 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. 2015;10(3):034006.

    PubMed  PubMed Central  Google Scholar 

  152. Lin DSY, Guo F, Zhang B. Modeling organ-specific vasculature with organ-on-a-chip devices. Nanotechnology. 2019;30(2):024002.

    PubMed  Google Scholar 

  153. 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. 2016;16(2):282–90.

    PubMed  PubMed Central  Google Scholar 

  154. 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.

    PubMed  PubMed Central  Google Scholar 

  155. 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.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine and Georgia Institute of Technology, 1760 Haygood Dr. NE, HSRB Bldg., Suite E480, Atlanta, GA, 30322, USA

    Martin L. Tomov, Carmen J. Gil, Alexander Cetnar, Andrea S. Theus, Bryanna J. Lima, Joy E. Nish & Vahid Serpooshan

  2. Division of Pediatric Cardiology, Children’s Healthcare of Atlanta Sibley Heart Center, Atlanta, GA, 30322, USA

    Holly D. Bauser-Heaton

  3. Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30309, USA

    Vahid Serpooshan

  4. Children’s Healthcare of Atlanta, Atlanta, GA, 30322, USA

    Vahid Serpooshan

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Martin L. Tomov, Carmen J. Gil, Alexander Cetnar, Andrea S. Theus, Bryanna J. Lima, Joy E. Nish, Holly D. Bauser-Heaton, and Vahid Serpooshan declare that they have no conflict of interest.

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Tomov, M.L., Gil, C.J., Cetnar, A. et al. Engineering Functional Cardiac Tissues for Regenerative Medicine Applications. Curr Cardiol Rep 21, 105 (2019). https://doi.org/10.1007/s11886-019-1178-9

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