Cardiac Tissue Engineering Systems: Comparison
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Please note this is a comparison between Version 2 by Conner Chen and Version 1 by Angel Raya.

Cardiac tissue engineering is very much in a current focus of regenerative medicine research as it represents a promising strategy for cardiac disease modelling, cardiotoxicity testing and cardiovascular repair. Advances in this field over the last two decades have enabled the generation of human engineered cardiac tissue constructs with progressively increased functional capabilities. Numerous studies have demonstrated that the therapeutic benefits exerted by cells are mainly attributable to the release of complementary paracrine factors and the efficacy is limited as only a small percentage of transplanted cells engrafted in the infarcted tissue. Studies on animal models showed that combining cell therapy with tissue engineering techniques for the creation of cell sheets and patches, can increase stem cell survival and boost therapeutic action. Therefore, tissue engineering has been considered as a potential approach for cardiac regeneration after MI. 

  • cardiac tissue engineering
  • human heart
  • tissue maturation
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References

  1. Shimizu, T.; Yamato, M.; Isoi, Y.; Akutsu, T.; Setomaru, T.; Abe, K.; Kikuchi, A.; Umezu, M.; Okano, T. Fabrication of Pulsa-tile Cardiac Tissue Grafts Using a Novel 3-Dimensional Cell Sheet Manipulation Technique and Temperature-Responsive Cell Culture Surfaces. Circ. Res. 2002, 90, e40, doi:10.1161/hh0302.105722.
  2. Yamato, M.; Okano, T. Cell sheet engineering. Mater. Today 2004, 7, 42–47, doi:10.1016/S1369-7021(04)00234-2.
  3. Yang, J.; Yamato, M.; Kohno, C.; Nishimoto, A.; Sekine, H.; Fukai, F.; Okano, T. Cell Sheet Engineering: Recreating Tissues without Biodegradable Scaffolds. Biomaterials 2005, 26, 6415–6422.
  4. Shimizu, T.; Yamato, M.; Kikuchi, A.; Okano, T. Cell Sheet Engineering for Myocardial Tissue Reconstruction. Biomaterials 2003, 24, 2309–2316, doi:10.1016/s0142-9612(03)00110-8.
  5. Sekine, H.; Shimizu, T.; Dobashi, I.; Matsuura, K.; Hagiwara, N.; Takahashi, M.; Kobayashi, E.; Yamato, M.; Okano, T. Cardi-ac Cell Sheet Transplantation Improves Damaged Heart Function via Superior Cell Survival in Comparison with Dissociat-ed Cell Injection. Tissue Eng. Part A 2011, 17, 2973–2980, doi:10.1089/ten.tea.2010.0659.
  6. Sekine, H.; Shimizu, T.; Sakaguchi, K.; Dobashi, I.; Wada, M.; Yamato, M.; Kobayashi, E.; Umezu, M.; Okano, T. In Vitro Fab-rication of Functional Three-Dimensional Tissues with Perfusable Blood Vessels. Nat. Commun. 2013, 4, 1399, doi:10.1038/ncomms2406.
  7. Kawatou, M.; Masumoto, H.; Fukushima, H.; Morinaga, G.; Sakata, R.; Ashihara, T.; Yamashita, J.K. Modelling Torsade de Pointes Arrhythmias In Vitro in 3D Human iPS Cell-Engineered Heart Tissue. Nat. Commun. 2017, 8, 1078, doi:10.1038/s41467-017-01125-y.
  8. Sawa, Y.; Yoshikawa, Y.; Toda, K.; Fukushima, S.; Yamazaki, K.; Ono, M.; Sakata, Y.; Hagiwara, N.; Kinugawa, K.; Miyaga-wa, S. Safety and Efficacy of Autologous Skeletal Myoblast Sheets (TCD-51073) for the Treatment of Severe Chronic Heart Failure Due to Ischemic Heart Disease. Circ. J. 2015, 79, 991–999, doi:10.1253/circj.CJ-15-0243.
  9. Yui, Y. Concerns on a New Therapy for Severe Heart Failure Using Cell Sheets with Skeletal Muscle or Myocardial Cells from iPS Cells in Japan. NPJ Regen Med 2018, 3, 7, doi:10.1038/s41536-018-0047-2.
  10. Pomeroy, J.E.; Helfer, A.; Bursac, N. Biomaterializing the Promise of Cardiac Tissue Engineering. Biotechnol. Adv. 2019, doi:10.1016/j.biotechadv.2019.02.009.
  11. Shadrin, I.Y.; Allen, B.W.; Qian, Y.; Jackman, C.P.; Carlson, A.L.; Juhas, M.E.; Bursac, N. Cardiopatch Platform Enables Matu-ration and Scale-Up of Human Pluripotent Stem Cell-Derived Engineered Heart Tissues. Nat. Commun. 2017, 8, 1825, doi:10.1038/s41467-017-01946-x.
  12. Radisic, M.; Park, H.; Shing, H.; Consi, T.; Schoen, F.J.; Langer, R.; Freed, L.E.; Vunjak-Novakovic, G. Functional Assembly of Engineered Myocardium by Electrical Stimulation of Cardiac Myocytes Cultured on Scaffolds. Proc. Natl. Acad. Sci. USA. 2004, 101, 18129–18134, doi:10.1073/pnas.0407817101.
  13. Tandon, N.; Cannizzaro, C.; Chao, P.-H.G.; Maidhof, R.; Marsano, A.; Au, H.T.H.; Radisic, M.; Vunjak-Novakovic, G. Electri-cal Stimulation Systems for Cardiac Tissue Engineering. Nat. Protoc. 2009, 4, 155–173, doi:10.1038/nprot.2008.183.
  14. Barash, Y.; Dvir, T.; Tandeitnik, P.; Ruvinov, E.; Guterman, H.; Cohen, S. Electric Field Stimulation Integrated into Perfusion Bioreactor for Cardiac Tissue Engineering. Tissue Eng. Part C Methods 2010, 16, 1417–1426, doi:10.1089/ten.TEC.2010.0068.
  15. Maidhof, R.; Tandon, N.; Lee, E.J.; Luo, J.; Duan, Y.; Yeager, K.; Konofagou, E.; Vunjak-Novakovic, G. Biomimetic Perfusion and Electrical Stimulation Applied in Concert Improved the Assembly of Engineered Cardiac Tissue. J. Tissue Eng. Regen. Med. 2012, 6, e12–23, doi:10.1002/term.525.
  16. Bursac, N.; Papadaki, M.; Cohen, R.J.; Schoen, F.J.; Eisenberg, S.R.; Carrier, R.; Vunjak-Novakovic, G.; Freed, L.E. Cardiac Muscle Tissue Engineering: Toward an In Vitro Model for Electrophysiological Studies. Am. J. Physiol. Heart Circul. Physiol. 1999, 277, H433–H444.
  17. Radisic, M.; Park, H.; Martens, T.P.; Salazar-Lazaro, J.E.; Geng, W.; Wang, Y.; Langer, R.; Freed, L.E.; Vunjak-Novakovic, G. Pre-treatment of Synthetic Elastomeric Scaffolds by Cardiac Fibroblasts Improves Engineered Heart Tissue. J. Biomed. Mater. Res. A 2008, 86, 713–724, doi:10.1002/jbm.a.31578.
  18. Zandonella, C. Tissue Engineering: The Beat Goes On. Nature 2003, 421, 884–886, doi:10.1038/421884a.
  19. Sultana, N.; Hassan, M.I.; Lim, M.M. Scaffolding Biomaterials. In Composite Synthetic Scaffolds for Tissue Engineering and Regenerative Medicine; Sultana, N., Hassan, M.I., Lim, M.M., Eds.; Springer International Publishing: Cham, Switzerland, 2015; pp. 1–11 ISBN 9783319097558.
  20. Badrossamay, M.R.; McIlwee, H.A.; Goss, J.A.; Parker, K.K. Nanofiber Assembly by Rotary Jet-Spinning. Nano Lett. 2010, 10, 2257–2261.
  21. Kenar, H.; Kose, G.T.; Toner, M.; Kaplan, D.L.; Hasirci, V. A 3D Aligned Microfibrous Myocardial Tissue Construct Cultured Under Transient Perfusion. Biomaterials 2011, 32, 5320–5329, doi:10.1016/j.biomaterials.2011.04.025.
  22. Papadaki, M.; Bursac, N.; Langer, R.; Merok, J.; Vunjak-Novakovic, G.; Freed, L.E. Tissue Engineering of Functional Cardiac Muscle: Molecular, Structural, and Electrophysiological Studies. Am. J. Physiol. Heart Circul. Physiol. 2001, 280, H168–H178.
  23. Bursac, N.; Loo, Y.; Leong, K.; Tung, L. Novel Anisotropic Engineered Cardiac Tissues: Studies of Electrical Propagation. Biochem. Biophys. Res. Commun. 2007, 361, 847–853, doi:10.1016/j.bbrc.2007.07.138.
  24. Carrier, R.L.; Rupnick, M.; Langer, R.; Schoen, F.J.; Freed, L.E.; Vunjak-Novakovic, G. Perfusion Improves Tissue Architec-ture of Engineered Cardiac Muscle. Tissue Eng. 2002, 8, 175–188, doi:10.1089/107632702753724950.
  25. Radisic, M.; Yang, L.; Boublik, J.; Cohen, R.J.; Langer, R.; Freed, L.E.; Vunjak-Novakovic, G. Medium Perfusion Enables En-gineering of Compact and Contractile Cardiac Tissue. Am. J. Physiol. Heart Circ. Physiol. 2004, 286, H507–16, doi:10.1152/ajpheart.00171.2003.
  26. Radisic, M.; Marsano, A.; Maidhof, R.; Wang, Y.; Vunjak-Novakovic, G. Cardiac Tissue Engineering Using Perfusion Bioreac-tor Systems. Nat. Protoc. 2008, 3, 719–738, doi:10.1038/nprot.2008.40.
  27. Shachar, M.; Benishti, N.; Cohen, S. Effects of Mechanical Stimulation Induced by Compression and Medium Perfusion on Cardiac Tissue Engineering. Biotechnol. Prog. 2012, 28, 1551–1559, doi:10.1002/btpr.1633.
  28. O’Brien, F.J. Biomaterials & Scaffolds for Tissue Engineering. Mater. Today 2011, 14, 88–95, doi:10.1016/S1369-7021(11)70058-X.
  29. Gaetani, R.; Doevendans, P.A.; Metz, C.H.G.; Alblas, J.; Messina, E.; Giacomello, A.; Sluijter, J.P.G. Cardiac Tissue Engineer-ing Using Tissue Printing Technology and Human Cardiac Progenitor Cells. Biomaterials 2012, 33, 1782–1790, doi:10.1016/j.biomaterials.2011.11.003.
  30. Liberski, A.; Latif, N.; Raynaud, C.; Bollensdorff, C.; Yacoub, M. Alginate for Cardiac Regeneration: From Seaweed to Clini-cal Trials. Glob Cardiol Sci Pract 2016, 2016, e201604, doi:10.21542/gcsp.2016.4.
  31. Fleischer, S.; Shapira, A.; Feiner, R.; Dvir, T. Modular Assembly of Thick Multifunctional Cardiac Patches. Proc. Natl. Acad. Sci. USA. 2017, 114, 1898–1903, doi:10.1073/pnas.1615728114.
  32. Fleischer, S.; Shapira, A.; Regev, O.; Nseir, N.; Zussman, E.; Dvir, T. Albumin Fiber Scaffolds for Engineering Functional Cardiac Tissues. Biotechnol. Bioeng. 2014, 111, 1246–1257, doi:10.1002/bit.25185.
  33. Bian, W.; Jackman, C.P.; Bursac, N. Controlling the Structural and Functional Anisotropy of Engineered Cardiac Tissues. Biofabrication 2014, 6, 024109.
  34. Liu, Y.; Wang, L.; Kikuiri, T.; Akiyama, K.; Chen, C.; Xu, X.; Yang, R.; Chen, W.; Wang, S.; Shi, S. Mesenchymal Stem Cell-Based Tissue Regeneration is Governed by Recipient T Lymphocytes via IFN-γ and TNF-α. Nat. Med. 2011, 17, 1594–1601, doi:10.1038/nm.2542.
  35. Zhang, D.; Shadrin, I.Y.; Lam, J.; Xian, H.-Q.; Snodgrass, H.R.; Bursac, N. Tissue-engineered Cardiac Patch for Advanced Functional Maturation of Human ESC-Derived Cardiomyocytes. Biomaterials 2013, 34, 5813–5820, doi:10.1016/j.biomaterials.2013.04.026.
  36. Radisic, M.; Euloth, M.; Yang, L.; Langer, R.; Freed, L.E.; Vunjak-Novakovic, G. High-Density Seeding of Myocyte Cells for Cardiac Tissue Engineering. Biotechnol. Bioeng. 2003, 82, 403–414, Doi:10.1002/Bit.10594.
  37. Valls-Margarit, M.; Iglesias-García, O.; Di Guglielmo, C.; Sarlabous, L.; Tadevosyan, K.; Paoli, R.; Comelles, J.; Blanco-Almazán, D.; Jiménez-Delgado, S.; Castillo-Fernández, O.; et al. Engineered Macroscale Cardiac Constructs Elicit Human Myocardial Tissue-like Functionality. Stem Cell Rep. 2019, 13, 207–220, doi:10.1016/j.stemcr.2019.05.024.
  38. Yu, Y.; Alkhawaji, A.; Ding, Y.; Mei, J. Decellularized Scaffolds in Regenerative Medicine. Oncotarget 2016, 7, 58671–58683.
  39. Hodgson, M.J.; Knutson, C.C.; Momtahan, N.; Cook, A.D. Extracellular Matrix from Whole Porcine Heart Decellularization for Cardiac Tissue Engineering. Methods Mol. Biol. 2017, 95–102, doi:10.1007/7651_2017_31.
  40. Fontana, G.; Gershlak, J.; Adamski, M.; Lee, J.-S.; Matsumoto, S.; Le, H.D.; Binder, B.; Wirth, J.; Gaudette, G.; Murphy, W.L. Biofunctionalized Plants as Diverse Biomaterials for Human Cell Culture. Adv. Healthc. Mater. 2017, 6, doi:10.1002/adhm.201601225.
  41. Modulevsky, D.J.; Lefebvre, C.; Haase, K.; Al-Rekabi, Z.; Pelling, A.E. Apple Derived Cellulose Scaffolds for 3D Mammalian Cell Culture. PLos ONE 2014, 9, e97835, doi:10.1371/journal.pone.0097835.
  42. Modulevsky, D.J.; Cuerrier, C.M.; Pelling, A.E. Biocompatibility of Subcutaneously Implanted Plant-Derived Cellulose Biomaterials. PLos ONE 2016, 11, e0157894, doi:10.1371/journal.pone.0157894.
  43. Gershlak, J.R.; Hernandez, S.; Fontana, G.; Perreault, L.R.; Hansen, K.J.; Larson, S.A.; Binder, B.Y.K.; Dolivo, D.M.; Yang, T.; Dominko, T.; et al. Crossing Kingdoms: Using Decellularized Plants as Perfusable Tissue Engineering Scaffolds. Biomaterials 2017, 125, 13–22.
  44. Entcheva, E.; Bien, H.; Yin, L.; Chung, C.-Y.; Farrell, M.; Kostov, Y. Functional Cardiac Cell Constructs on Cellulose-Based Scaffolding. Biomaterials 2004, 25, 5753–5762, doi:10.1016/j.biomaterials.2004.01.024.
  45. Wippermann, J.; Schumann, D.; Klemm, D.; Albes, J.M.; Wittwer, T.; Strauch, J.; Wahlers, T. Preliminary Results of Small Arterial Substitutes Performed with a New Cylindrical Biomaterial Composed of Bacterial Cellulose. Thorac. Cardiovasc. Surg. 2008, 56, 592–596.
  46. Oberwallner, B.; Brodarac, A.; Anić, P.; Šarić, T.; Wassilew, K.; Neef, K.; Choi, Y.-H.; Stamm, C. Human Cardiac Extracellular Matrix Supports Myocardial Lineage Commitment of Pluripotent Stem Cells. Eur. J. Cardiothorac. Surg. 2015, 47, 416–25; dis-cussion 425, doi:10.1093/ejcts/ezu163.
  47. Kc, P.; Hong, Y.; Zhang, G. Cardiac Tissue-Derived Extracellular Matrix Scaffolds for Myocardial Repair: Advantages and Challenges. Regen Biomater 2019, 6, 185–199, doi:10.1093/rb/rbz017.
  48. Oberwallner, B.; Brodarac, A.; Choi, Y.-H.; Saric, T.; Anić, P.; Morawietz, L.; Stamm, C. Preparation of Cardiac Extracellular Matrix Scaffolds by Decellularization of Human Myocardium. J. Biomed. Mater. Res. A 2014, 102, 3263–3272, doi:10.1002/jbma.35000.
  49. Garreta, E.; de Oñate, L.; Fernández-Santos, M.E.; Oria, R.; Tarantino, C.; Climent, A.M.; Marco, A.; Samitier, M.; Martínez, E.; Valls-Margarit, M.; et al. Myocardial Commitment From Human Pluripotent Stem Cells: Rapid Production Of Human Heart Grafts. Biomaterials 2016, 98, 64–78, doi:10.1016/j.biomaterials.2016.04.003.
  50. Sánchez, P.L.; Fernández-Santos, M.E.; Costanza, S.; Climent, A.M.; Moscoso, I.; Gonzalez-Nicolas, M.A.; Sanz-Ruiz, R.; Rodríguez, H.; Kren, S.M.; Garrido, G.; et al. Acellular Human Heart Matrix: A Critical Step Toward Whole Heart Grafts. Bi-omaterials 2015, 61, 279–289, doi:10.1016/j.biomaterials.2015.04.056.
  51. Guyette, J.P.; Charest, J.M.; Mills, R.W.; Jank, B.J.; Moser, P.T.; Gilpin, S.E.; Gershlak, J.R.; Okamoto, T.; Gonzalez, G.; Milan, D.J.; et al. Bioengineering Human Myocardium on Native Extracellular Matrix. Circ. Res. 2016, 118, 56–72, doi:10.1161/CIRCRESAHA.115.306874.
  52. Pedron, S.; Van Lierop, S.; Horstman, P.; Penterman, R.; Broer, D.J.; Peeters, E. Stimuli Responsive Delivery Vehicles for Cardiac Microtissue Transplantation. Adv. Funct. Mater. 2011, 21, 1624–1630, doi:10.1002/adfm.201002708.
  53. Birla, R.K.; Borschel, G.H.; Dennis, R.G.; Brown, D.L. Myocardial Engineering in Vivo: Formation and Characterization of Contractile, Vascularized Three-Dimensional Cardiac Tissue. Tissue Eng. 2005, 11, 803–813.
  54. Sepantafar, M.; Maheronnaghsh, R.; Mohammadi, H.; Rajabi-Zeleti, S.; Annabi, N.; Aghdami, N.; Baharvand, H. Stem Cells and Injectable Hydrogels: Synergistic Therapeutics in Myocardial Repair. Biotechnol. Adv. 2016, 34, 362–379, doi:10.1016/j.biotechadv.2016.03.003.
  55. Riegler, J.; Tiburcy, M.; Ebert, A.; Tzatzalos, E.; Raaz, U.; Abilez, O.J.; Shen, Q.; Kooreman, N.G.; Neofytou, E.; Chen, V.C.; et al. Human Engineered Heart Muscles Engraft and Survive Long Term in a Rodent Myocardial Infarction Model. Circ. Res. 2015, 117, 720–730, doi:10.1161/CIRCRESAHA.115.306985.
  56. Weinberger, F.; Breckwoldt, K.; Pecha, S.; Kelly, A.; Geertz, B.; Starbatty, J.; Yorgan, T.; Cheng, K.-H.; Lessmann, K.; Stolen, T.; et al. Cardiac Repair in Guinea Pigs with Human Engineered Heart Tissue from Induced Pluripotent Stem Cells. Sci. Transl. Med. 2016, 8, 363ra148, doi:10.1126/scitranslmed.aaf8781.
  57. Zimmermann, W.-H.; Melnychenko, I.; Wasmeier, G.; Didié, M.; Naito, H.; Nixdorff, U.; Hess, A.; Budinsky, L.; Brune, K.; Michaelis, B.; et al. Engineered Heart Tissue Grafts Improve Systolic and Diastolic Function in Infarcted Rat Hearts. Nat. Med. 2006, 12, 452–458, doi:10.1038/nm1394.
  58. Kopeček, J.; Yang, J. Smart Self-Assembled Hybrid Hydrogel Biomaterials. Angew. Chem. Int. Ed. 2012, 51, 7396–7417.
  59. Camci-Unal, G.; Annabi, N.; Dokmeci, M.R.; Liao, R.; Khademhosseini, A. Hydrogels for Cardiac Tissue Engineering. NPG Asia Mater. 2014, 6, e99–e99, doi:10.1038/am.2014.19.
  60. Hansen, A.; Eder, A.; Bönstrup, M.; Flato, M.; Mewe, M.; Schaaf, S.; Aksehirlioglu, B.; Schwörer, A.; Uebeler, J.; Eschenhagen, T. Development of a Drug Screening Platform Based on Engineered Heart Tissue. Circ. Res. 2010, 107, 35–44.
  61. Tulloch, N.L.; Muskheli, V.; Razumova, M.V.; Korte, F.S.; Regnier, M.; Hauch, K.D.; Pabon, L.; Reinecke, H.; Murry, C.E. Growth of Engineered Human Myocardium with Mechanical Loading and Vascular Coculture. Circ. Res. 2011, 109, 47–59, doi:10.1161/CIRCRESAHA.110.237206.
  62. Nunes, S.S.; Miklas, J.W.; Liu, J.; Aschar-Sobbi, R.; Xiao, Y.; Zhang, B.; Jiang, J.; Massé, S.; Gagliardi, M.; Hsieh, A.; et al. Bio-wire: a Platform for Maturation of Human Pluripotent Stem Cell–Derived Cardiomyocytes. Nat. Methods 2013, 10, 781–787.
  63. Jackman, C.P.; Carlson, A.L.; Bursac, N. Dynamic Culture Yields Engineered Myocardium with Near-Adult Functional Out-put. Biomaterials 2016, 111, 66–79, doi:10.1016/j.biomaterials.2016.09.024.
  64. Nakane, T.; Masumoto, H.; Tinney, J.P.; Yuan, F.; Kowalski, W.J.; Ye, F.; LeBlanc, A.J.; Sakata, R.; Yamashita, J.K.; Keller, B.B. Impact of Cell Composition and Geometry on Human Induced Pluripotent Stem Cells-Derived Engineered Cardiac Tissue. Sci. Rep. 2017, 7, 45641, doi:10.1038/srep45641.
  65. Tiburcy, M.; Hudson, J.E.; Balfanz, P.; Schlick, S.; Meyer, T.; Chang Liao, M.-L.; Levent, E.; Raad, F.; Zeidler, S.; Wingender, E.; et al. Defined Engineered Human Myocardium with Advanced Maturation for Applications in Heart Failure Modeling and Repair. Circulation 2017, 135, 1832–1847, doi:10.1161/CIRCULATIONAHA.116.024145.
  66. Ronaldson-Bouchard, K.; Ma, S.P.; Yeager, K.; Chen, T.; Song, L.; Sirabella, D.; Morikawa, K.; Teles, D.; Yazawa, M.; Vunjak-Novakovic, G. Author Correction: Advanced Maturation of Human Cardiac Tissue Grown from Pluripotent Stem Cells. Na-ture 2019, 572, E16–E17, doi:10.1038/s41586-019-1415-9.
  67. Black, L.D., 3rd; Meyers, J.D.; Weinbaum, J.S.; Shvelidze, Y.A.; Tranquillo, R.T. Cell-Induced Alignment Augments Twitch Force in Fibrin Gel-Based Engineered Myocardium via Gap Junction Modification. Tissue Eng. Part A 2009, 15, 3099–3108, doi:10.1089/ten.TEA.2008.0502.
  68. Hansen, K.J.; Laflamme, M.A.; Gaudette, G.R. Development of a Contractile Cardiac Fiber from Pluripotent Stem Cell De-rived Cardiomyocytes. Front Cardiovasc Med 2018, 5, 52, doi:10.3389/fcvm.2018.00052.
  69. Naito, H.; Melnychenko, I.; Didié, M.; Schneiderbanger, K.; Schubert, P.; Rosenkranz, S.; Eschenhagen, T.; Zimmermann, W.-H. Optimizing Engineered Heart Tissue for Therapeutic Applications as Surrogate Heart Muscle. Circulation 2006, 114, I72–8, doi:10.1161/CIRCULATIONAHA.105.001560.
  70. Zimmermann, W.-H.; Didié, M.; Wasmeier, G.H.; Nixdorff, U.; Hess, A.; Melnychenko, I.; Boy, O.; Neuhuber, W.L.; Weyand, M.; Eschenhagen, T. Cardiac Grafting of Engineered Heart Tissue in Syngenic Rats. Circulation 2002, 106, I151–I157.
  71. Kensah, G.; Gruh, I.; Viering, J.; Schumann, H.; Dahlmann, J.; Meyer, H.; Skvorc, D.; Bär, A.; Akhyari, P.; Heisterkamp, A.; et al. A Novel Miniaturized Multimodal Bioreactor for Continuous In Situ Assessment of Bioartificial Cardiac Tissue During Stimulation and Maturation. Tissue Eng. Part C Methods 2011, 17, 463–473, doi:10.1089/ten.TEC.2010.0405.
  72. Schaaf, S.; Shibamiya, A.; Mewe, M.; Eder, A.; Stöhr, A.; Hirt, M.N.; Rau, T.; Zimmermann, W.-H.; Conradi, L.; Eschenhagen, T.; et al. Human Engineered Heart Tissue as a Versatile Tool in Basic Research and Preclinical Toxicology. PLos ONE 2011, 6, e26397, doi:10.1371/journal.pone.0026397.
  73. Thavandiran, N.; Dubois, N.; Mikryukov, A.; Massé, S.; Beca, B.; Simmons, C.A.; Deshpande, V.S.; McGarry, J.P.; Chen, C.S.; Nanthakumar, K.; et al. Design and Formulation of Functional Pluripotent Stem Cell-Derived Cardiac Microtissues. Proc. Natl. Acad. Sci. USA. 2013, 110, E4698–707, doi:10.1073/pnas.1311120110.
  74. Turnbull, I.C.; Karakikes, I.; Serrao, G.W.; Backeris, P.; Lee, J.-J.; Xie, C.; Senyei, G.; Gordon, R.E.; Li, R.A.; Akar, F.G.; et al. Advancing Functional Engineered Cardiac Tissues Toward a Preclinical Model of Human Myocardium. FASEB J. 2014, 28, 644–654, doi:10.1096/fj.13-228007.
  75. Mannhardt, I.; Breckwoldt, K.; Letuffe-Brenière, D.; Schaaf, S.; Schulz, H.; Neuber, C.; Benzin, A.; Werner, T.; Eder, A.; Schul-ze, T.; et al. Human Engineered Heart Tissue: Analysis of Contractile Force. Stem Cell Reports 2016, 7, 29–42, doi:10.1016/j.stemcr.2016.04.011.
  76. Ruan, J.-L.; Tulloch, N.L.; Razumova, M.V.; Saiget, M.; Muskheli, V.; Pabon, L.; Reinecke, H.; Regnier, M.; Murry, C.E. Me-chanical Stress Conditioning and Electrical Stimulation Promote Contractility and Force Maturation of Induced Pluripotent Stem Cell-Derived Human Cardiac Tissue. Circulation 2016, 134, 1557–1567, doi:10.1161/CIRCULATIONAHA.114.014998.
  77. Lemoine, M.D.; Mannhardt, I.; Breckwoldt, K.; Prondzynski, M.; Flenner, F.; Ulmer, B.; Hirt, M.N.; Neuber, C.; Horváth, A.; Kloth, B.; et al. Human iPSC-Derived Cardiomyocytes Cultured in 3D Engineered Heart Tissue Show Physiological Up-stroke Velocity and Sodium Current Density. Sci. Rep. 2017, 7, 5464, doi:10.1038/s41598-017-05600-w.
  78. Gao, L.; Gregorich, Z.R.; Zhu, W.; Mattapally, S.; Oduk, Y.; Lou, X.; Kannappan, R.; Borovjagin, A.V.; Walcott, G.P.; Pollard, A.E.; et al. Large Cardiac Muscle Patches Engineered from Human Induced-Pluripotent Stem Cell-Derived Cardiac Cells Improve Recovery from Myocardial Infarction in Swine. Circulation 2018, 137, 1712–1730, doi:10.1161/CIRCULATIONAHA.117.030785.
  79. Xiao, Y.; Zhang, B.; Liu, H.; Miklas, J.W.; Gagliardi, M.; Pahnke, A.; Thavandiran, N.; Sun, Y.; Simmons, C.; Keller, G.; et al. Microfabricated Perfusable Cardiac Biowire: a Platform that Mimics Native Cardiac Bundle. Lab Chip 2014, 14, 869–882, doi:10.1039/c3lc51123e.
  80. Ma, Z.; Koo, S.; Finnegan, M.A.; Loskill, P.; Huebsch, N.; Marks, N.C.; Conklin, B.R.; Grigoropoulos, C.P.; Healy, K.E. Three-Dimensional Filamentous Human Diseased Cardiac Tissue Model. Biomaterials 2014, 35, 1367–1377, doi:10.1016/j.biomaterials.2013.10.052.
  81. Ma, Z.; Wang, J.; Loskill, P.; Huebsch, N.; Koo, S.; Svedlund, F.L.; Marks, N.C.; Hua, E.W.; Grigoropoulos, C.P.; Conklin, B.R.; et al. Self-Organizing Human Cardiac Microchambers Mediated by Geometric Confinement. Nat. Commun. 2015, 6, 7413, doi:10.1038/ncomms8413.
  82. Lau, H.K.; Kiick, K.L. Opportunities for Multicomponent Hybrid Hydrogels in Biomedical Applications. Biomacromolecules 2015, 16, 28–42.
  83. Fennema, E.; Rivron, N.; Rouwkema, J.; van Blitterswijk, C.; de Boer, J. Spheroid Culture as a Tool for Creating 3D Complex Tissues. Trends Biotechnol. 2013, 31, 108–115.
  84. Beauchamp, P.; Moritz, W.; Kelm, J.M.; Ullrich, N.D.; Agarkova, I.; Anson, B.D.; Suter, T.M.; Zuppinger, C. Development and Characterization of a Scaffold-Free 3D Spheroid Model of Induced Pluripotent Stem Cell-Derived Human Cardiomyocytes. Tissue Eng. Part C Methods 2015, 21, 852–861, doi:10.1089/ten.TEC.2014.0376.
  85. Nguyen, D.C.; Hookway, T.A.; Wu, Q.; Jha, R.; Preininger, M.K.; Chen, X.; Easley, C.A.; Spearman, P.; Deshpande, S.R.; Ma-her, K.; et al. Microscale Generation of Cardiospheres Promotes Robust Enrichment of Cardiomyocytes Derived from Hu-man Pluripotent Stem Cells. Stem Cell Reports 2014, 3, 260–268, doi:10.1016/j.stemcr.2014.06.002.
  86. Kofron, C.M.; Kim, T.Y.; King, M.E.; Xie, A.; Feng, F.; Park, E.; Qu, Z.; -R. Choi, B.; Mende, U. Gq-Activated Fibroblasts In-duce Cardiomyocyte Action Potential Prolongation and Automaticity in a Three-Dimensional Microtissue Environment. Am. J. Physiol. Heart Circ. Physiol. 2017, 313, H810–H827.
  87. Giacomelli, E.; Bellin, M.; Sala, L.; van Meer, B.J.; Tertoolen, L.G.J.; Orlova, V.V.; Mummery, C.L. Three-Dimensional Cardi-ac Microtissues Composed of Cardiomyocytes and Endothelial Cells Co-Differentiated from Human Pluripotent Stem Cells. Development 2017, 144, 1008–1017, doi:10.1242/dev.143438.
  88. Yan, Y.; Bejoy, J.; Xia, J.; Griffin, K.; Guan, J.; Li, Y. Cell Population Balance of Cardiovascular Spheroids Derived from Hu-man Induced Pluripotent Stem Cells. Sci. Rep. 2019, 9, 1295, doi:10.1038/s41598-018-37686-1.
  89. Oltolina, F.; Zamperone, A.; Colangelo, D.; Gregoletto, L.; Reano, S.; Pietronave, S.; Merlin, S.; Talmon, M.; Novelli, E.; Di-ena, M.; et al. Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential. PLos ONE 2015, doi:10.1371/journal.pone.0141632.
  90. Mattapally, S.; Zhu, W.; Fast, V.G.; Gao, L.; Worley, C.; Kannappan, R.; Borovjagin, A.V.; Zhang, J. Spheroids of Cardiomyo-cytes Derived from Human-Induced Pluripotent Stem Cells Improve Recovery from Myocardial Injury in Mice. Am. J. Phys-iol. Heart Circul. Physiol. 2018, 315, H327–H339.
  91. Noguchi, R.; Nakayama, K.; Itoh, M.; Kamohara, K.; Furukawa, K.; Oyama, J.-I.; Node, K.; Morita, S. Development of a Three-Dimensional Pre-Vascularized Scaffold-Free Contractile Cardiac Patch for Treating Heart Disease. J. Heart Lung Transplant. 2016, 35, 137–145, doi:10.1016/j.healun.2015.06.001.
  92. Ong, C.S.; Fukunishi, T.; Zhang, H.; Huang, C.Y.; Nashed, A.; Blazeski, A.; DiSilvestre, D.; Vricella, L.; Conte, J.; Tung, L.; et al. Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes. Sci. Rep. 2017, 7, 4566, doi:10.1038/s41598-017-05018-4.
  93. Kim, T.Y.; Kofron, C.M.; King, M.E.; Markes, A.R.; Okundaye, A.O.; Qu, Z.; Mende, U.; Choi, B.-R. Directed Fusion of Cardiac Spheroids into Larger Heterocellular Microtissues Enables Investigation of Cardiac Action Potential Propagation via Car-diac Fibroblasts. PLos ONE 2018, 13, e0196714.
  94. Lancaster, M.A.; Knoblich, J.A. Organogenesis in a Dish: Modeling Development and Disease Using Organoid Technologies. Science 2014, 345, 1247125.
  95. Evans, M. Discovering Pluripotency: 30 Years of Mouse Embryonic Stem Cells. Nat. Rev. Mol. Cell Biol. 2011, 12, 680–686.
  96. Knight, E.; Przyborski, S. Advances in 3D Cell Culture Technologies Enabling Tissue-Like Structures to Be Created In Vitro. J. Anat. 2015, 227, 746–756.
  97. Shkumatov, A.; Baek, K.; Kong, H. Matrix Rigidity-Modulated Cardiovascular Organoid Formation from Embryoid Bodies. PLos ONE 2014, 9, e94764, doi:10.1371/journal.pone.0094764.
  98. Mills, R.J.; Parker, B.L.; Quaife-Ryan, G.A.; Voges, H.K.; Needham, E.J.; Bornot, A.; Ding, M.; Andersson, H.; Polla, M.; El-liott, D.A.; et al. Drug Screening in Human PSC-Cardiac Organoids Identifies Pro-Proliferative Compounds Acting via the Mevalonate Pathway. Cell Stem Cell 2019, 24, 895–907.e6, doi:10.1016/j.stem.2019.03.009.
  99. Hoang, P.; Wang, J.; Conklin, B.R.; Healy, K.E.; Ma, Z. Generation of Spatial-Patterned Early-Developing Cardiac Organoids Using Human Pluripotent Stem Cells. Nat. Protoc. 2018, 13, 723–737, doi:10.1038/nprot.2018.006.
  100. Varzideh, F.; Pahlavan, S.; Ansari, H.; Halvaei, M.; Kostin, S.; Feiz, M.-S.; Latifi, H.; Aghdami, N.; Braun, T.; Baharvand, H. Human Cardiomyocytes Undergo Enhanced Maturation in Embryonic Stem Cell-Derived Organoid Transplants. Biomateri-als 2019, 192, 537–550, doi:10.1016/j.biomaterials.2018.11.033.
  101. Richards, D.J.; Li, Y.; Kerr, C.M.; Yao, J.; Beeson, G.C.; Coyle, R.C.; Chen, X.; Jia, J.; Damon, B.; Wilson, R.; et al. Human Car-diac Organoids for the Modelling of Myocardial Infarction and Drug Cardiotoxicity. Nat. Biomed. Eng 2020, 4, 446–462, doi:10.1038/s41551-020-0539-4.
  102. Richards, D.J.; Coyle, R.C.; Tan, Y.; Jia, J.; Wong, K.; Toomer, K.; Menick, D.R.; Mei, Y. Inspiration from Heart Development: Biomimetic Development of Functional Human Cardiac Organoids. Biomaterials 2017, 142, 112–123, doi:10.1016/j.biomaterials.2017.07.021.
  103. Lee, J.; Sutani, A.; Kaneko, R.; Takeuchi, J.; Sasano, T.; Kohda, T.; Ihara, K.; Takahashi, K.; Yamazoe, M.; Morio, T.; et al. In Vitro Generation of Functional Murine Heart Organoids via FGF4 and Extracellular Matrix. Nat. Commun. 2020, 11, 4283, doi:10.1038/s41467-020-18031-5.
  104. Huh, D.; Torisawa, Y.-S.; Hamilton, G.A.; Kim, H.J.; Ingber, D.E. Microengineered Physiological Biomimicry: Organs-on-Chips. Lab Chip 2012, 12, 2156–2164, doi:10.1039/c2lc40089h.
  105. Ewart, L.; Dehne, E.-M.; Fabre, K.; Gibbs, S.; Hickman, J.; Hornberg, E.; Ingelman-Sundberg, M.; Jang, K.-J.; Jones, D.R.; Lauschke, V.M.; et al. Application of Microphysiological Systems to Enhance Safety Assessment in Drug Discovery. Annu. Rev. Pharmacol. Toxicol. 2018, 58, 65–82.
  106. Zhang, X.; Wang, Q.; Gablaski, B.; Zhang, X.; Lucchesi, P.; Zhao, Y. A Microdevice for Studying Intercellular Electromechani-cal Transduction in Adult Cardiac Myocytes. Lab Chip 2013, 13, 3090–3097, doi:10.1039/c3lc50414j.
  107. Jastrzebska, E.; Tomecka, E.; Jesion, I. Heart-on-a-Chip Based on Stem Cell Biology. Biosens. Bioelectron. 2016, 75, 67–81, doi:10.1016/j.bios.2015.08.012.
  108. Ribas, J.; Sadeghi, H.; Manbachi, A.; Leijten, J.; Brinegar, K.; Zhang, Y.S.; Ferreira, L.; Khademhosseini, A. Cardiovascular Organ-on-a-Chip Platforms for Drug Discovery and Development. Appl In Vitro Toxicol 2016, 2, 82–96, doi:10.1089/aivt.2016.0002.
  109. Kujala, V.J.; Pasqualini, F.S.; Goss, J.A.; Nawroth, J.C.; Parker, K.K. Laminar Ventricular Myocardium on a Microelectrode Array-Based Chip. J. Mater. Chem. B Mater. Biol. Med. 2016, 4, 3534–3543, doi:10.1039/C6TB00324A.
  110. Chen, Y.; Chan, H.N.; Michael, S.A.; Shen, Y.; Chen, Y.; Tian, Q.; Huang, L.; Wu, H. A Microfluidic Circulatory System Inte-grated with Capillary-Assisted Pressure Sensors. Lab Chip 2017, 17, 653–662, doi:10.1039/c6lc01427e.
  111. Ghiaseddin, A.; Pouri, H.; Soleimani, M.; Vasheghani-Farahani, E.; Ahmadi Tafti, H.; Hashemi-Najafabadi, S. Cell Laden Hydrogel Construct on-a-Chip for Mimicry of Cardiac Tissue in-Vitro Study. Biochem. Biophys. Res. Commun. 2017, 484, 225–230, doi:10.1016/j.bbrc.2017.01.029.
  112. Simmons, C.S.; Petzold, B.C.; Pruitt, B.L. Microsystems for Biomimetic Stimulation of Cardiac Cells. Lab Chip 2012, 12, 3235–3248, doi:10.1039/c2lc40308k.
  113. Kobuszewska, A.; Tomecka, E.; Zukowski, K.; Jastrzebska, E.; Chudy, M.; Dybko, A.; Renaud, P.; Brzozka, Z. Heart-on-a-Chip: An Investigation of the Influence of Static and Perfusion Conditions on Cardiac (H9C2) Cell Proliferation, Morpholo-gy, and Alignment. SLAS Technol 2017, 22, 536–546, doi:10.1177/2472630317705610.
  114. Zhao, Y.; Rafatian, N.; Feric, N.T.; Cox, B.J.; Aschar-Sobbi, R.; Wang, E.Y.; Aggarwal, P.; Zhang, B.; Conant, G.; Ronaldson-Bouchard, K.; et al. A Platform for Generation of Chamber-Specific Cardiac Tissues and Disease Modeling. Cell 2019, 176, 913–927.e18, doi:10.1016/j.cell.2018.11.042.
  115. Nguyen, M.-D.; Tinney, J.P.; Ye, F.; Elnakib, A.A.; Yuan, F.; El-Baz, A.; Sethu, P.; Keller, B.B.; Giridharan, G.A. Effects of Phys-iologic Mechanical Stimulation on Embryonic Chick Cardiomyocytes Using a Microfluidic Cardiac Cell Culture Model. Anal. Chem. 2015, 87, 2107–2113, doi:10.1021/ac503716z.
  116. Marsano, A.; Conficconi, C.; Lemme, M.; Occhetta, P.; Gaudiello, E.; Votta, E.; Cerino, G.; Redaelli, A.; Rasponi, M. Beating Heart on a Chip: A Novel Microfluidic Platform to Generate Functional 3D Cardiac Microtissues. Lab Chip 2016, 16, 599–610, doi:10.1039/c5lc01356a.
  117. Grosberg, A.; Alford, P.W.; McCain, M.L.; Parker, K.K. Ensembles of Engineered Cardiac Tissues for Physiological and Pharmacological Study: Heart on a Chip. Lab Chip 2011, 11, 4165–4173, doi:10.1039/c1lc20557a.
  118. Tu, C.; Chao, B.S.; Wu, J.C. Strategies for Improving the Maturity of Human Induced Pluripotent Stem Cell-Derived Cardi-omyocytes. Circ. Res. 2018, 123, 512–514, doi:10.1161/CIRCRESAHA.118.313472.
  119. Zhang, Y.S.; Aleman, J.; Arneri, A.; Bersini, S.; Piraino, F.; Shin, S.R.; Dokmeci, M.R.; Khademhosseini, A. From Cardiac Tis-sue Engineering to Heart-on-a-Chip: Beating Challenges. Biomed. Mater. 2015, 10, 034006, doi:10.1088/1748-6041/10/3/034006.
  120. Chu, X.; Bleasby, K.; Evers, R. Species Differences in Drug Transporters and Implications for Translating Preclinical Find-ings to Humans. Expert Opin. Drug Metab. Toxicol. 2013, 9, 237–252, doi:10.1517/17425255.2013.741589.
  121. Hirt, M.N.; Boeddinghaus, J.; Mitchell, A.; Schaaf, S.; Börnchen, C.; Müller, C.; Schulz, H.; Hubner, N.; Stenzig, J.; Stoehr, A.; et al. Functional Improvement and Maturation of Rat and Human Engineered Heart Tissue by Chronic Electrical Stimula-tion. J. Mol. Cell. Cardiol. 2014, 74, 151–161, doi:10.1016/j.yjmcc.2014.05.009.
  122. Zhang, B.; Montgomery, M.; Chamberlain, M.D.; Ogawa, S.; Korolj, A.; Pahnke, A.; Wells, L.A.; Massé, S.; Kim, J.; Reis, L.; et al. Biodegradable Scaffold with Built-In Vasculature for Organ-on-a-Chip Engineering and Direct Surgical Anastomosis.
  123. Nat. Mater. 2016, 15, 669–678, doi:10.1038/nmat4570.
  124. Mathur, A.; Loskill, P.; Shao, K.; Huebsch, N.; Hong, S.; Marcus, S.G.; Marks, N.; Mandegar, M.; Conklin, B.R.; Lee, L.P.; et al. Human iPSC-Based Cardiac Microphysiological System for Drug Screening Applications. Sci. Rep. 2015, 5, 8883, doi:10.1038/srep08883.
  125. Homan, K.A.; Kolesky, D.B.; Skylar-Scott, M.A.; Herrmann, J.; Obuobi, H.; Moisan, A.; Lewis, J.A. Bioprinting of 3D Convo-luted Renal Proximal Tubules on Perfusable Chips. Sci. Rep. 2016, 6, 34845.
  126. Kolesky, D.B.; Homan, K.A.; Skylar-Scott, M.A.; Lewis, J.A. Three-Dimensional Bioprinting of Thick Vascularized Tissues. Proc. Natl. Acad. Sci. USA 2016, 113, 3179–3184, doi:10.1073/pnas.1521342113.
  127. Dhariwala, B.; Hunt, E.; Boland, T. Rapid Prototyping of Tissue-Engineering Constructs, Using Photopolymerizable Hydro-gels and Stereolithography. Tissue Eng. 2004, 10, 1316–1322, doi:10.1089/ten.2004.10.1316.
  128. Boland, T.; Xu, T.; Damon, B.; Cui, X. Application of Inkjet Printing to Tissue Engineering. Biotechnol. J. 2006, 1, 910–917, doi:10.1002/biot.200600081.
  129. Yan, J.; Huang, Y.; Chrisey, D.B. Laser-Assisted Printing of Alginate Long Tubes and Annular Constructs. Biofabrication 2013, 5, 015002, doi:10.1088/1758-5082/5/1/015002.
  130. Beyer, S.T.; Bsoul, A.; Ahmadi, A.; Walus, K. 3D Alginate Constructs for Tissue Engineering Printed Using a Coaxial Flow Focusing Microfluidic Device. 2013 Transducers & Eurosensors XXVII: The 17th International Conference on Solid-State Sen-sors, Actuators and Microsystems (TRANSDUCERS & EUROSENSORS XXVII), Barcelona, 2013, pp. 1206–1209, doi: 10.1109/Transducers.2013.6626990.
  131. Gaetani, R.; Feyen, D.A.M.; Verhage, V.; Slaats, R.; Messina, E.; Christman, K.L.; Giacomello, A.; Doevendans, P.A.F.M.; Sluijter, J.P.G. Epicardial Application of Cardiac Progenitor Cells in a 3D-Printed Gelatin/Hyaluronic Acid Patch Preserves Cardiac Function after Myocardial Infarction. Biomaterials 2015, 61, 339–348, doi:10.1016/j.biomaterials.2015.05.005.
  132. Noor, N.; Shapira, A.; Edri, R.; Gal, I.; Wertheim, L.; Dvir, T. 3D Printing of Personalized Thick and Perfusable Cardiac Patches and Hearts. Adv. Sci. 2019, 6, 1900344, doi:10.1002/advs.201900344.
  133. Maiullari, F.; Costantini, M.; Milan, M.; Pace, V.; Chirivì, M.; Maiullari, S.; Rainer, A.; Baci, D.; Marei, H.E.-S.; Seliktar, D.; et al. A Multi-Cellular 3D Bioprinting Approach for Vascularized Heart Tissue Engineering Based on HUVECs and iPSC-Derived Cardiomyocytes. Sci. Rep. 2018, 8, 13532, doi:10.1038/s41598-018-31848-x.
  134. Lee, H.; Cho, D.-W. One-Step Fabrication of an Organ-on-a-Chip with Spatial Heterogeneity Using a 3D Bioprinting Tech-nology. Lab Chip 2016, 16, 2618–2625, doi:10.1039/c6lc00450d.
  135. Bhardwaj, N.; Kundu, S.C. Electrospinning: A Fascinating Fiber Fabrication Technique. Biotechnol. Adv. 2010, 28, 325–347, doi:10.1016/j.biotechadv.2010.01.004.
  136. Huang, S.; Yang, Y.; Yang, Q.; Zhao, Q.; Ye, X. Engineered Circulatory Scaffolds for Building Cardiac Tissue. J. Thorac. Dis. 2018, 10, S2312–S2328, doi:10.21037/jtd.2017.12.92.
  137. Castilho, M.; Hochleitner, G.; Wilson, W.; van Rietbergen, B.; Dalton, P.D.; Groll, J.; Malda, J.; Ito, K. Mechanical Behavior of a Soft Hydrogel Reinforced with Three-Dimensional Printed Microfibre Scaffolds. Sci. Rep. 2018, 8, 1245, doi:10.1038/s41598-018-19502-y.
  138. Yildirim, Y.; Naito, H.; Didie, M.; Karikkineth, B.C.; Biermann, D.; Eschenhagen, T.; -H. Zimmermann, W. Development of a Biological Ventricular Assist Device: Preliminary Data from a Small Animal Model. Circulation 2007, 116, I16–I23.
  139. Lee, E.J.; Kim, D.E.; Azeloglu, E.U.; Costa, K.D. Engineered Cardiac Organoid Chambers: Toward a Functional Biological Model Ventricle. Tissue Eng. Part A 2008, 14, 215–225.
  140. Li, R.A.; Keung, W.; Cashman, T.J.; Backeris, P.C.; Johnson, B.V.; Bardot, E.S.; Wong, A.O.T.; Chan, P.K.W.; Chan, C.W.Y.; Costa, K.D. Bioengineering an Electro-Mechanically Functional Miniature Ventricular Heart Chamber from Human Plu-ripotent Stem Cells. Biomaterials 2018, 163, 116–127, doi:10.1016/j.biomaterials.2018.02.024.
  141. MacQueen, L.A.; Sheehy, S.P.; Chantre, C.O.; Zimmerman, J.F.; Pasqualini, F.S.; Liu, X.; Goss, J.A.; Campbell, P.H.; Gonzalez, G.M.; Park, S.-J.; et al. A Tissue-Engineered Scale Model of the Heart Ventricle. Nat. Biomed. Eng. 2018, 2, 930–941.
  142. Lee, A.; Hudson, A.R.; Shiwarski, D.J.; Tashman, J.W.; Hinton, T.J.; Yerneni, S.; Bliley, J.M.; Campbell, P.G.; Feinberg, A.W. 3D Bioprinting of Collagen to Rebuild Components of the Human Heart. Science 2019, 365, 482–487, doi:10.1126/science.aav9051.
  143. Kopeček, J.; Yang, J. Smart Self-Assembled Hybrid Hydrogel Biomaterials. Angew. Chem. Int. Ed. 2012, 51, 7396–7417.
  144. Camci-Unal, G.; Annabi, N.; Dokmeci, M.R.; Liao, R.; Khademhosseini, A. Hydrogels for Cardiac Tissue Engineering. NPG Asia Mater. 2014, 6, e99–e99, doi:10.1038/am.2014.19.
  145. Black, L.D., 3rd; Meyers, J.D.; Weinbaum, J.S.; Shvelidze, Y.A.; Tranquillo, R.T. Cell-Induced Alignment Augments Twitch Force in Fibrin Gel-Based Engineered Myocardium via Gap Junction Modification. Tissue Eng. Part A 2009, 15, 3099–3108, doi:10.1089/ten.TEA.2008.0502.
  146. Hansen, K.J.; Laflamme, M.A.; Gaudette, G.R. Development of a Contractile Cardiac Fiber from Pluripotent Stem Cell De-rived Cardiomyocytes. Front Cardiovasc Med 2018, 5, 52, doi:10.3389/fcvm.2018.00052.
  147. Naito, H.; Melnychenko, I.; Didié, M.; Schneiderbanger, K.; Schubert, P.; Rosenkranz, S.; Eschenhagen, T.; Zimmermann, W.-H. Optimizing Engineered Heart Tissue for Therapeutic Applications as Surrogate Heart Muscle. Circulation 2006, 114, I72–8, doi:10.1161/CIRCULATIONAHA.105.001560.
  148. Lau, H.K.; Kiick, K.L. Opportunities for Multicomponent Hybrid Hydrogels in Biomedical Applications. Biomacromolecules 2015, 16, 28–42.
  149. Fennema, E.; Rivron, N.; Rouwkema, J.; van Blitterswijk, C.; de Boer, J. Spheroid Culture as a Tool for Creating 3D Complex Tissues. Trends Biotechnol. 2013, 31, 108–115.
  150. Beauchamp, P.; Moritz, W.; Kelm, J.M.; Ullrich, N.D.; Agarkova, I.; Anson, B.D.; Suter, T.M.; Zuppinger, C. Development and Characterization of a Scaffold-Free 3D Spheroid Model of Induced Pluripotent Stem Cell-Derived Human Cardiomyocytes. Tissue Eng. Part C Methods 2015, 21, 852–861, doi:10.1089/ten.TEC.2014.0376.
  151. Nguyen, D.C.; Hookway, T.A.; Wu, Q.; Jha, R.; Preininger, M.K.; Chen, X.; Easley, C.A.; Spearman, P.; Deshpande, S.R.; Ma-her, K.; et al. Microscale Generation of Cardiospheres Promotes Robust Enrichment of Cardiomyocytes Derived from Hu-man Pluripotent Stem Cells. Stem Cell Reports 2014, 3, 260–268, doi:10.1016/j.stemcr.2014.06.002.
  152. Kofron, C.M.; Kim, T.Y.; King, M.E.; Xie, A.; Feng, F.; Park, E.; Qu, Z.; -R. Choi, B.; Mende, U. Gq-Activated Fibroblasts In-duce Cardiomyocyte Action Potential Prolongation and Automaticity in a Three-Dimensional Microtissue Environment. Am. J. Physiol. Heart Circ. Physiol. 2017, 313, H810–H827.
  153. Yan, Y.; Bejoy, J.; Xia, J.; Griffin, K.; Guan, J.; Li, Y. Cell Population Balance of Cardiovascular Spheroids Derived from Hu-man Induced Pluripotent Stem Cells. Sci. Rep. 2019, 9, 1295, doi:10.1038/s41598-018-37686-1.
  154. Polonchuk, L.; Chabria, M.; Badi, L.; Hoflack, J.-C.; Figtree, G.; Davies, M.J.; Gentile, C. Cardiac Spheroids as Promising In Vitro Models to Study the Human Heart Microenvironment. Sci. Rep. 2017, 7, 7005.
  155. Oltolina, F.; Zamperone, A.; Colangelo, D.; Gregoletto, L.; Reano, S.; Pietronave, S.; Merlin, S.; Talmon, M.; Novelli, E.; Di-ena, M.; et al. Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential. PLos ONE 2015, doi:10.1371/journal.pone.0141632.
  156. Mattapally, S.; Zhu, W.; Fast, V.G.; Gao, L.; Worley, C.; Kannappan, R.; Borovjagin, A.V.; Zhang, J. Spheroids of Cardiomyo-cytes Derived from Human-Induced Pluripotent Stem Cells Improve Recovery from Myocardial Injury in Mice. Am. J. Phys-iol. Heart Circul. Physiol. 2018, 315, H327–H339.
  157. Noguchi, R.; Nakayama, K.; Itoh, M.; Kamohara, K.; Furukawa, K.; Oyama, J.-I.; Node, K.; Morita, S. Development of a Three-Dimensional Pre-Vascularized Scaffold-Free Contractile Cardiac Patch for Treating Heart Disease. J. Heart Lung Transplant. 2016, 35, 137–145, doi:10.1016/j.healun.2015.06.001.
  158. Ong, C.S.; Fukunishi, T.; Zhang, H.; Huang, C.Y.; Nashed, A.; Blazeski, A.; DiSilvestre, D.; Vricella, L.; Conte, J.; Tung, L.; et al. Biomaterial-Free Three-Dimensional Bioprinting of Cardiac Tissue using Human Induced Pluripotent Stem Cell Derived Cardiomyocytes. Sci. Rep. 2017, 7, 4566, doi:10.1038/s41598-017-05018-4.
  159. Kim, T.Y.; Kofron, C.M.; King, M.E.; Markes, A.R.; Okundaye, A.O.; Qu, Z.; Mende, U.; Choi, B.-R. Directed Fusion of Cardiac Spheroids into Larger Heterocellular Microtissues Enables Investigation of Cardiac Action Potential Propagation via Car-diac Fibroblasts. PLos ONE 2018, 13, e0196714.
  160. Lancaster, M.A.; Knoblich, J.A. Organogenesis in a Dish: Modeling Development and Disease Using Organoid Technologies. Science 2014, 345, 1247125.
  161. Evans, M. Discovering Pluripotency: 30 Years of Mouse Embryonic Stem Cells. Nat. Rev. Mol. Cell Biol. 2011, 12, 680–686.
  162. Knight, E.; Przyborski, S. Advances in 3D Cell Culture Technologies Enabling Tissue-Like Structures to Be Created In Vitro. J. Anat. 2015, 227, 746–756.
  163. Shkumatov, A.; Baek, K.; Kong, H. Matrix Rigidity-Modulated Cardiovascular Organoid Formation from Embryoid Bodies. PLos ONE 2014, 9, e94764, doi:10.1371/journal.pone.0094764.
  164. Mills, R.J.; Parker, B.L.; Quaife-Ryan, G.A.; Voges, H.K.; Needham, E.J.; Bornot, A.; Ding, M.; Andersson, H.; Polla, M.; El-liott, D.A.; et al. Drug Screening in Human PSC-Cardiac Organoids Identifies Pro-Proliferative Compounds Acting via the Mevalonate Pathway. Cell Stem Cell 2019, 24, 895–907.e6, doi:10.1016/j.stem.2019.03.009.
  165. Hoang, P.; Wang, J.; Conklin, B.R.; Healy, K.E.; Ma, Z. Generation of Spatial-Patterned Early-Developing Cardiac Organoids Using Human Pluripotent Stem Cells. Nat. Protoc. 2018, 13, 723–737, doi:10.1038/nprot.2018.006.
  166. Varzideh, F.; Pahlavan, S.; Ansari, H.; Halvaei, M.; Kostin, S.; Feiz, M.-S.; Latifi, H.; Aghdami, N.; Braun, T.; Baharvand, H. Human Cardiomyocytes Undergo Enhanced Maturation in Embryonic Stem Cell-Derived Organoid Transplants. Biomateri-als 2019, 192, 537–550, doi:10.1016/j.biomaterials.2018.11.033.
  167. Richards, D.J.; Li, Y.; Kerr, C.M.; Yao, J.; Beeson, G.C.; Coyle, R.C.; Chen, X.; Jia, J.; Damon, B.; Wilson, R.; et al. Human Car-diac Organoids for the Modelling of Myocardial Infarction and Drug Cardiotoxicity. Nat. Biomed. Eng 2020, 4, 446–462, doi:10.1038/s41551-020-0539-4.
  168. Richards, D.J.; Coyle, R.C.; Tan, Y.; Jia, J.; Wong, K.; Toomer, K.; Menick, D.R.; Mei, Y. Inspiration from Heart Development: Biomimetic Development of Functional Human Cardiac Organoids. Biomaterials 2017, 142, 112–123, doi:10.1016/j.biomaterials.2017.07.021.
  169. Lee, J.; Sutani, A.; Kaneko, R.; Takeuchi, J.; Sasano, T.; Kohda, T.; Ihara, K.; Takahashi, K.; Yamazoe, M.; Morio, T.; et al. In Vitro Generation of Functional Murine Heart Organoids via FGF4 and Extracellular Matrix. Nat. Commun. 2020, 11, 4283, doi:10.1038/s41467-020-18031-5.
  170. Huh, D.; Torisawa, Y.-S.; Hamilton, G.A.; Kim, H.J.; Ingber, D.E. Microengineered Physiological Biomimicry: Organs-on-Chips. Lab Chip 2012, 12, 2156–2164, doi:10.1039/c2lc40089h.
  171. Ewart, L.; Dehne, E.-M.; Fabre, K.; Gibbs, S.; Hickman, J.; Hornberg, E.; Ingelman-Sundberg, M.; Jang, K.-J.; Jones, D.R.; Lauschke, V.M.; et al. Application of Microphysiological Systems to Enhance Safety Assessment in Drug Discovery. Annu. Rev. Pharmacol. Toxicol. 2018, 58, 65–82.
  172. Jastrzebska, E.; Tomecka, E.; Jesion, I. Heart-on-a-Chip Based on Stem Cell Biology. Biosens. Bioelectron. 2016, 75, 67–81, doi:10.1016/j.bios.2015.08.012.
  173. Ribas, J.; Sadeghi, H.; Manbachi, A.; Leijten, J.; Brinegar, K.; Zhang, Y.S.; Ferreira, L.; Khademhosseini, A. Cardiovascular Organ-on-a-Chip Platforms for Drug Discovery and Development. Appl In Vitro Toxicol 2016, 2, 82–96, doi:10.1089/aivt.2016.0002.
  174. Kujala, V.J.; Pasqualini, F.S.; Goss, J.A.; Nawroth, J.C.; Parker, K.K. Laminar Ventricular Myocardium on a Microelectrode Array-Based Chip. J. Mater. Chem. B Mater. Biol. Med. 2016, 4, 3534–3543, doi:10.1039/C6TB00324A.
  175. Chen, Y.; Chan, H.N.; Michael, S.A.; Shen, Y.; Chen, Y.; Tian, Q.; Huang, L.; Wu, H. A Microfluidic Circulatory System Inte-grated with Capillary-Assisted Pressure Sensors. Lab Chip 2017, 17, 653–662, doi:10.1039/c6lc01427e.
  176. Ghiaseddin, A.; Pouri, H.; Soleimani, M.; Vasheghani-Farahani, E.; Ahmadi Tafti, H.; Hashemi-Najafabadi, S. Cell Laden Hydrogel Construct on-a-Chip for Mimicry of Cardiac Tissue in-Vitro Study. Biochem. Biophys. Res. Commun. 2017, 484, 225–230, doi:10.1016/j.bbrc.2017.01.029.
  177. Simmons, C.S.; Petzold, B.C.; Pruitt, B.L. Microsystems for Biomimetic Stimulation of Cardiac Cells. Lab Chip 2012, 12, 3235–3248, doi:10.1039/c2lc40308k.
  178. Kobuszewska, A.; Tomecka, E.; Zukowski, K.; Jastrzebska, E.; Chudy, M.; Dybko, A.; Renaud, P.; Brzozka, Z. Heart-on-a-Chip: An Investigation of the Influence of Static and Perfusion Conditions on Cardiac (H9C2) Cell Proliferation, Morpholo-gy, and Alignment. SLAS Technol 2017, 22, 536–546, doi:10.1177/2472630317705610.
  179. Nguyen, M.-D.; Tinney, J.P.; Ye, F.; Elnakib, A.A.; Yuan, F.; El-Baz, A.; Sethu, P.; Keller, B.B.; Giridharan, G.A. Effects of Phys-iologic Mechanical Stimulation on Embryonic Chick Cardiomyocytes Using a Microfluidic Cardiac Cell Culture Model. Anal. Chem. 2015, 87, 2107–2113, doi:10.1021/ac503716z.
  180. Marsano, A.; Conficconi, C.; Lemme, M.; Occhetta, P.; Gaudiello, E.; Votta, E.; Cerino, G.; Redaelli, A.; Rasponi, M. Beating Heart on a Chip: A Novel Microfluidic Platform to Generate Functional 3D Cardiac Microtissues. Lab Chip 2016, 16, 599–610, doi:10.1039/c5lc01356a.
  181. Grosberg, A.; Alford, P.W.; McCain, M.L.; Parker, K.K. Ensembles of Engineered Cardiac Tissues for Physiological and Pharmacological Study: Heart on a Chip. Lab Chip 2011, 11, 4165–4173, doi:10.1039/c1lc20557a.
  182. Tu, C.; Chao, B.S.; Wu, J.C. Strategies for Improving the Maturity of Human Induced Pluripotent Stem Cell-Derived Cardi-omyocytes. Circ. Res. 2018, 123, 512–514, doi:10.1161/CIRCRESAHA.118.313472.
  183. Zhang, Y.S.; Aleman, J.; Arneri, A.; Bersini, S.; Piraino, F.; Shin, S.R.; Dokmeci, M.R.; Khademhosseini, A. From Cardiac Tis-sue Engineering to Heart-on-a-Chip: Beating Challenges. Biomed. Mater. 2015, 10, 034006, doi:10.1088/1748-6041/10/3/034006.
  184. Chu, X.; Bleasby, K.; Evers, R. Species Differences in Drug Transporters and Implications for Translating Preclinical Find-ings to Humans. Expert Opin. Drug Metab. Toxicol. 2013, 9, 237–252, doi:10.1517/17425255.2013.741589.
  185. Hirt, M.N.; Boeddinghaus, J.; Mitchell, A.; Schaaf, S.; Börnchen, C.; Müller, C.; Schulz, H.; Hubner, N.; Stenzig, J.; Stoehr, A.; et al. Functional Improvement and Maturation of Rat and Human Engineered Heart Tissue by Chronic Electrical Stimula-tion. J. Mol. Cell. Cardiol. 2014, 74, 151–161, doi:10.1016/j.yjmcc.2014.05.009.
  186. Zhang, B.; Montgomery, M.; Chamberlain, M.D.; Ogawa, S.; Korolj, A.; Pahnke, A.; Wells, L.A.; Massé, S.; Kim, J.; Reis, L.; et al. Biodegradable Scaffold with Built-In Vasculature for Organ-on-a-Chip Engineering and Direct Surgical Anastomosis.
  187. Nat. Mater. 2016, 15, 669–678, doi:10.1038/nmat4570.
  188. Mathur, A.; Loskill, P.; Shao, K.; Huebsch, N.; Hong, S.; Marcus, S.G.; Marks, N.; Mandegar, M.; Conklin, B.R.; Lee, L.P.; et al. Human iPSC-Based Cardiac Microphysiological System for Drug Screening Applications. Sci. Rep. 2015, 5, 8883, doi:10.1038/srep08883.
  189. Homan, K.A.; Kolesky, D.B.; Skylar-Scott, M.A.; Herrmann, J.; Obuobi, H.; Moisan, A.; Lewis, J.A. Bioprinting of 3D Convo-luted Renal Proximal Tubules on Perfusable Chips. Sci. Rep. 2016, 6, 34845.
  190. Kolesky, D.B.; Homan, K.A.; Skylar-Scott, M.A.; Lewis, J.A. Three-Dimensional Bioprinting of Thick Vascularized Tissues. Proc. Natl. Acad. Sci. USA 2016, 113, 3179–3184, doi:10.1073/pnas.1521342113.
  191. Dhariwala, B.; Hunt, E.; Boland, T. Rapid Prototyping of Tissue-Engineering Constructs, Using Photopolymerizable Hydro-gels and Stereolithography. Tissue Eng. 2004, 10, 1316–1322, doi:10.1089/ten.2004.10.1316.
  192. Boland, T.; Xu, T.; Damon, B.; Cui, X. Application of Inkjet Printing to Tissue Engineering. Biotechnol. J. 2006, 1, 910–917, doi:10.1002/biot.200600081.
  193. Yan, J.; Huang, Y.; Chrisey, D.B. Laser-Assisted Printing of Alginate Long Tubes and Annular Constructs. Biofabrication 2013, 5, 015002, doi:10.1088/1758-5082/5/1/015002.
  194. Beyer, S.T.; Bsoul, A.; Ahmadi, A.; Walus, K. 3D Alginate Constructs for Tissue Engineering Printed Using a Coaxial Flow Focusing Microfluidic Device. 2013 Transducers & Eurosensors XXVII: The 17th International Conference on Solid-State Sen-sors, Actuators and Microsystems (TRANSDUCERS & EUROSENSORS XXVII), Barcelona, 2013, pp. 1206–1209, doi: 10.1109/Transducers.2013.6626990.
  195. Gaetani, R.; Feyen, D.A.M.; Verhage, V.; Slaats, R.; Messina, E.; Christman, K.L.; Giacomello, A.; Doevendans, P.A.F.M.; Sluijter, J.P.G. Epicardial Application of Cardiac Progenitor Cells in a 3D-Printed Gelatin/Hyaluronic Acid Patch Preserves Cardiac Function after Myocardial Infarction. Biomaterials 2015, 61, 339–348, doi:10.1016/j.biomaterials.2015.05.005.
  196. Maiullari, F.; Costantini, M.; Milan, M.; Pace, V.; Chirivì, M.; Maiullari, S.; Rainer, A.; Baci, D.; Marei, H.E.-S.; Seliktar, D.; et al. A Multi-Cellular 3D Bioprinting Approach for Vascularized Heart Tissue Engineering Based on HUVECs and iPSC-Derived Cardiomyocytes. Sci. Rep. 2018, 8, 13532, doi:10.1038/s41598-018-31848-x.
  197. Lee, H.; Cho, D.-W. One-Step Fabrication of an Organ-on-a-Chip with Spatial Heterogeneity Using a 3D Bioprinting Tech-nology. Lab Chip 2016, 16, 2618–2625, doi:10.1039/c6lc00450d.
  198. Bhardwaj, N.; Kundu, S.C. Electrospinning: A Fascinating Fiber Fabrication Technique. Biotechnol. Adv. 2010, 28, 325–347, doi:10.1016/j.biotechadv.2010.01.004.
  199. Huang, S.; Yang, Y.; Yang, Q.; Zhao, Q.; Ye, X. Engineered Circulatory Scaffolds for Building Cardiac Tissue. J. Thorac. Dis. 2018, 10, S2312–S2328, doi:10.21037/jtd.2017.12.92.
  200. Castilho, M.; Hochleitner, G.; Wilson, W.; van Rietbergen, B.; Dalton, P.D.; Groll, J.; Malda, J.; Ito, K. Mechanical Behavior of a Soft Hydrogel Reinforced with Three-Dimensional Printed Microfibre Scaffolds. Sci. Rep. 2018, 8, 1245, doi:10.1038/s41598-018-19502-y.
  201. Yildirim, Y.; Naito, H.; Didie, M.; Karikkineth, B.C.; Biermann, D.; Eschenhagen, T.; -H. Zimmermann, W. Development of a Biological Ventricular Assist Device: Preliminary Data from a Small Animal Model. Circulation 2007, 116, I16–I23.
  202. Lee, E.J.; Kim, D.E.; Azeloglu, E.U.; Costa, K.D. Engineered Cardiac Organoid Chambers: Toward a Functional Biological Model Ventricle. Tissue Eng. Part A 2008, 14, 215–225.
  203. Li, R.A.; Keung, W.; Cashman, T.J.; Backeris, P.C.; Johnson, B.V.; Bardot, E.S.; Wong, A.O.T.; Chan, P.K.W.; Chan, C.W.Y.; Costa, K.D. Bioengineering an Electro-Mechanically Functional Miniature Ventricular Heart Chamber from Human Plu-ripotent Stem Cells. Biomaterials 2018, 163, 116–127, doi:10.1016/j.biomaterials.2018.02.024.
  204. MacQueen, L.A.; Sheehy, S.P.; Chantre, C.O.; Zimmerman, J.F.; Pasqualini, F.S.; Liu, X.; Goss, J.A.; Campbell, P.H.; Gonzalez, G.M.; Park, S.-J.; et al. A Tissue-Engineered Scale Model of the Heart Ventricle. Nat. Biomed. Eng. 2018, 2, 930–941.
  205. Lee, A.; Hudson, A.R.; Shiwarski, D.J.; Tashman, J.W.; Hinton, T.J.; Yerneni, S.; Bliley, J.M.; Campbell, P.G.; Feinberg, A.W. 3D Bioprinting of Collagen to Rebuild Components of the Human Heart. Science 2019, 365, 482–487, doi:10.1126/science.aav9051.
  206. Kupfer, M.E.; Lin, W.-H.; Ravikumar, V.; Qiu, K.; Wang, L.; Gao, L.; Bhuiyan, D.; Lenz, M.; Ai, J.; Mahutga, R.R.; et al. In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Or-ganoid. Circ. Res. 2020, doi:10.1161/CIRCRESAHA.119.316155.
  207. Garoffolo, G.; Pesce, M. Mechanotransduction in the Cardiovascular System: From Developmental Origins to Homeostasis and Pathology. Cells 2019, 8, doi:10.3390/cells8121607.
  208. Fink, C.; Ergün, S.; Kralisch, D.; Remmers, U.; Weil, J.; Eschenhagen, T. Chronic Stretch of Engineered Heart Tissue Induces Hypertrophy and Functional Improvement. FASEB J. 2000, 14, 669–679, doi:10.1096/fasebj.14.5.669.
  209. Lasher, R.A.; Pahnke, A.Q.; Johnson, J.M.; Sachse, F.B.; Hitchcock, R.W. Electrical Stimulation Directs Engineered Cardiac Tissue to an Age-Matched Native Phenotype. J. Tissue Eng. 2012, 3, doi:10.1177/2041731412455354.
  210. Ruwhof, C. Mechanical Stress-Induced Cardiac Hypertrophy: Mechanisms and Signal Transduction Pathways. Cardiovasc. Res. 2000, 47, 23–37.
  211. Severs, N.J. The cardiac Muscle Cell. Bioessays 2000, 22, 188–199, doi:10.1002/(SICI)1521-1878(200002)22:2<188::AID-BIES10>3.0.CO;2-T.
  212. Lie-Venema, H.; van den Akker, N.M.S.; Bax, N.A.M.; Winter, E.M.; Maas, S.; Kekarainen, T.; Hoeben, R.C.; DeRuiter, M.C.; Poelmann, R.E.; Gittenberger-de Groot, A.C. Origin, Fate, and Function of Epicardium-Derived Cells (EPDCs) in Normal and Abnormal Cardiac Development. Sci. World J. 2007, 7, 1777–1798, doi:10.1100/tsw.2007.294.
  213. Goette, A.; Lendeckel, U. Electrophysiological Effects of Angiotensin II. Part I: Signal Transduction and Basic Electrophysio-logical Mechanisms. Europace 2008, 10, 238–241, doi:10.1093/europace/eum283.
  214. Zhang, P.; Su, J.; Mende, U. Cross Talk between Cardiac Myocytes and Fibroblasts: From Multiscale Investigative Ap-proaches to Mechanisms and Functional Consequences. Am. J. Physiol. Heart Circ. Physiol. 2012, 303, H1385–H1396, doi:10.1152/ajpheart.01167.2011.
  215. Brutsaert, D.L. Cardiac Endothelial-Myocardial Signaling: Its Role in Cardiac Growth, Contractile Performance, and Rhythmicity. Physiol. Rev. 2003, 83, 59–115, doi:10.1152/physrev.00017.2002.
  216. Iyer, R.K.; Odedra, D.; Chiu, L.L.Y.; Vunjak-Novakovic, G.; Radisic, M. Vascular Endothelial Growth Factor Secretion by Nonmyocytes Modulates Connexin-43 Levels in Cardiac Organoids. Tissue Eng. Part A 2012, 18, 1771–1783, doi:10.1089/ten.TEA.2011.0468.
  217. Garzoni, L.R.; Rossi, M.I.D.; de Barros, A.P.D.N.; Guarani, V.; Keramidas, M.; Balottin, L.B.L.; Adesse, D.; Takiya, C.M.; Man-so, P.P.; Otazú, I.B.; et al. Dissecting Coronary Angiogenesis: 3D Co-Culture of Cardiomyocytes with Endothelial or Mesen-chymal Cells. Exp. Cell Res. 2009, 315, 3406–3418, doi:10.1016/j.yexcr.2009.09.016.
  218. Liau, B.; Zhang, D.; Bursac, N. Functional Cardiac Tissue Engineering. Regen. Med. 2012, 7, 187–206, doi:10.2217/rme.11.122.
  219. Xue, T.; Cho, H.C.; Akar, F.G.; Tsang, S.-Y.; Jones, S.P.; Marbán, E.; Tomaselli, G.F.; Li, R.A. Functional Integration of Electri-cally Active Cardiac Derivatives from Genetically Engineered Human Embryonic Stem Cells with Quiescent Recipient Ven-tricular Cardiomyocytes: Insights into the Development of Cell-Based Pacemakers. Circulation 2005, 111, 11–20, doi:10.1161/01.CIR.0000151313.18547.A2.
  220. Ponard, J.G.C.; Kondratyev, A.A.; Kucera, J.P. Mechanisms of Intrinsic Beating Variability in Cardiac Cell Cultures and Model Pacemaker Networks. Biophys. J. 2007, 92, 3734–3752, doi:10.1529/biophysj.106.091892.
  221. Radisic, M.; Fast, V.G.; Sharifov, O.F.; Iyer, R.K.; Park, H.; Vunjak-Novakovic, G. Optical Mapping of Impulse Propagation in Engineered Cardiac Tissue. Tissue Eng. Part A 2009, 15, 851–860.
  222. Schaffer, P.; Ahammer, H.; Müller, W.; Koidl, B.; Windisch, H. Di-4-ANEPPS Causes Photodynamic Damage to Isolated Car-diomyocytes. Pflug. Arch. 1994, 426, 548–551, doi:10.1007/BF00378533.
  223. Hamill, O.P.; Marty, A.; Neher, E.; Sakmann, B.; Sigworth, F.J. Improved Patch-Clamp Techniques for high-Resolution Cur-rent Recording from Cells and Cell-Free Membrane Patches. Pflug. Arch. 1981, 391, 85–100, doi:10.1007/BF00656997.
  224. Del Corsso, C.; Srinivas, M.; Urban-Maldonado, M.; Moreno, A.P.; Fort, A.G.; Fishman, G.I.; Spray, D.C. Transfection of Mammalian Cells with Connexins and Measurement of Voltage Sensitivity of Their Gap Junctions. Nat. Protoc. 2006, 1, 1799–1809, doi:10.1038/nprot.2006.266.
  225. Brown, K.T. Advanced Micropipette Techniques for Cell Physiology; Wiley: Hoboken, NJ, USA, 1986; ISBN 9780471909521.
  226. Kehat, I.; Gepstein, A.; Spira, A.; Itskovitz-Eldor, J.; Gepstein, L. High-Resolution Electrophysiological Assessment of Hu-man Embryonic Stem Cell-Derived Cardiomyocytes. Circ. Res. 2002, 91, 659–661.
  227. Reppel, M.; Pillekamp, F.; Brockmeier, K.; Matzkies, M.; Bekcioglu, A.; Lipke, T.; Nguemo, F.; Bonnemeier, H.; Hescheler, J. The Electrocardiogram of Human Embryonic Stem Cell-Derived Cardiomyocytes. J. Electrocardiol. 2005, 38, 166–170, doi:10.1016/j.jelectrocard.2005.06.029.
  228. Tung, L.; Zhang, Y. Optical Imaging of Arrhythmias in Tissue Culture. J. Electrocardiol. 2006, 39, S2–S6, doi:10.1016/j.jelectrocard.2006.04.010.
  229. Efimov, I.R.; Nikolski, V.P.; Salama, G. Optical Imaging of the Heart. Circ. Res. 2004, 95, 21–33, doi:10.1161/01.RES.0000130529.18016.35.
  230. Lieu, D.K.; Turnbull, I.C.; Costa, K.D.; Li, R.A. Engineered Human Pluripotent Stem Cell-Derived Cardiac Cells and Tissues for Electrophysiological Studies. Drug Discov. Today Dis. Models 2012, 9, e209–e217, doi:10.1016/j.ddmod.2012.06.002.
  231. Van Der Velden, J.; Klein, L.J.; Zaremba, R.; Boontje, N.M.; Huybregts, M.A.; Stooker, W.; Eijsman, L.; de Jong, J.W.; Visser, C.A.; Visser, F.C.; et al. Effects of Calcium, Inorganic Phosphate, and pH on Isometric Force in Single Skinned Cardiomyo-cytes from Donor and Failing Human Hearts. Circulation 2001, 104, 1140–1146, doi:10.1161/hc3501.095485.
  232. Karakikes, I.; Ameen, M.; Termglinchan, V.; Wu, J.C. Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: In-sights into Molecular, Cellular, and Functional Phenotypes. Circ. Res. 2015, 117, 80–88.
  233. Hunter, P.J.; Pullan, A.J.; Smaill, B.H. Modeling Total Heart Function. Annu. Rev. Biomed. Eng. 2003, 5, 147–177, doi:10.1146/annurev.bioeng.5.040202.121537.
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