Review Insights In Cardiac Tissue Engineering: Cells, Scaffolds, and Pharmacological Agents

Document Type : Review Paper


1 Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Department of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Protein Technology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Research Institute for Prevention of Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran.

5 Research Center for Advanced Technologies in Cardiovascular Medicine, Cardiovascular Diseases Research Institute, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.



Heart failure (HF) is one of the most important cardiovascular diseases (CVD), causing many die every year. Cardiac tissue engineering is a multidisciplinary field for creating functional tissues to improve the cardiac function of the damaged heart and get hope for end-stage patients. Recent works have focused on creating engineered cardiac tissue ex-vivo. Simultaneously, new approaches are used to study ways of induction of regeneration in the damaged heart after injury. The heart as a complex physiological pump consists of many cells such as cardiomyocytes (80–90% of the heart volume). These cardiomyocytes are elongated, aligned, and have beating properties. To create the heart muscle, which should be functional, soft and elastic scaffolds are required to resemble the native heart tissue. These mechanical characteristics are not compatible with all materials and should be well selected. Some scaffolds promote the viability and differentiation of stem cells. Each material has advantages and disadvantages with relevant influence behavior for cells. In this review, we present an overview of the general approaches developed to generate functional cardiac tissues, discussing the different cell sources, biomaterials, pharmacological agents, and engineering strategies in this manner. Moreover, we discuss the main challenges in cardiac tissue engineering that cause difficulties to construct heart muscle. We trust that researchers interested in developing cardiac tissue engineering will find the information reviewed here useful. Furthermore, we think that providing a unified framework will further the development of human engineered cardiac tissue constructs.

Graphical Abstract

Review Insights In Cardiac Tissue Engineering: Cells, Scaffolds, and Pharmacological Agents


(1)        Song X, Mei J, Ye G, Wang L, Ananth A, Yu L, and Qiu X. In situ pPy-modification of chitosan porous membrane from mussel shell as a cardiac patch to repair myocardial infarction. Applied Materials Today. (2019) 15: 87-99.
(2)        Zhang J, Zhu W, Radisic M, and Vunjak-Novakovic G. Can we engineer a human cardiac patch for therapy? Circulation research. (2018) 123: 244-65.
(3)        Salmons S and Jarvis JC. Cardiomyoplasty reviewed: Lessons from the past, prospects for the future. Basic Appl Myol. (2009) 19: 5-16.
(4)        Nguyen PK, Rhee J-W, and Wu JC. Adult Stem Cell Therapy and Heart Failure, 2000 to 2016: A Systematic Review. JAMA Cardiology. (2016) 1: 831-41.
(5)        Gao L, Gregorich ZR, Zhu W, Mattapally S, Oduk Y, Lou X, Kannappan R, Borovjagin AV, Walcott GP, and Pollard AE. Large cardiac muscle patches engineered from human induced-pluripotent stem cell–derived cardiac cells improve recovery from myocardial infarction in swine. Circulation. (2018) 137: 1712-30.
(6)        Ye L, Chang Y-H, Xiong Q, Zhang P, Zhang L, Somasundaram P, Lepley M, Swingen C, Su L, and Wendel JS. Cardiac repair in a porcine model of acute myocardial infarction with human induced pluripotent stem cell-derived cardiovascular cells. Cell stem cell. (2014) 15: 750-61.
(7)        Hudson W, Collins MC, Sun YS, Muller-Borer B, and Kypson AP. Beating and arrested intramyocardial injections are associated with significant mechanical loss: implications for cardiac cell transplantation. Journal of Surgical Research. (2007) 142: 263-7.
(8)        Zhang H, Song P, Tang Y, Zhang X-l, Zhao S-h, Wei Y-j, and Hu S-s. Injection of bone marrow mesenchymal stem cells in the borderline area of infarcted myocardium: heart status and cell distribution. The Journal of thoracic and cardiovascular surgery. (2007) 134: 1234-40. e1.
(9)        Kitsara M, Agbulut O, Kontziampasis D, Chen Y, and Menasché P. Fibers for hearts: A critical review on electrospinning for cardiac tissue engineering. Acta biomaterialia. (2017) 48: 20-40.
(10)      Li R-K, Jia Z-Q, Weisel RD, Mickle DA, Choi A, and Yau TM. Survival and function of bioengineered cardiac grafts. Circulation. (1999) 100: II-63-Ii-9.
(11)      Carrier RL, Papadaki M, Rupnick M, Schoen FJ, Bursac N, Langer R, Freed LE, and Vunjak‐Novakovic G. Cardiac tissue engineering: cell seeding, cultivation parameters, and tissue construct characterization. Biotechnology and bioengineering. (1999) 64: 580-9.
(12)      Bursac N, Papadaki M, Cohen R, Schoen F, Eisenberg S, Carrier R, Vunjak-Novakovic G, and Freed L. Cardiac muscle tissue engineering: toward an in vitro model for electrophysiological studies. American Journal of Physiology-Heart and Circulatory Physiology. (1999) 277: H433-H44.
(13)      Hamdi H, Furuta A, Bellamy V, Bel A, Puymirat E, Peyrard S, Agbulut O, and Menasché P. Cell delivery: intramyocardial injections or epicardial deposition? A head-to-head comparison. The Annals of thoracic surgery. (2009) 87: 1196-203.
(14)      Menasché P, Vanneaux V, Hagège A, Bel A, Cholley B, Cacciapuoti I, Parouchev A, Benhamouda N, Tachdjian G, and Tosca L. Human embryonic stem cell-derived cardiac progenitors for severe heart failure treatment: first clinical case report. European heart journal. (2015) 36: 2011-7.
(15)      Menasché P, Vanneaux V, Hagège A, Bel A, Cholley B, Parouchev A, Cacciapuoti I, Al-Daccak R, Benhamouda N, and Blons H. Transplantation of human embryonic stem cell–derived cardiovascular progenitors for severe ischemic left ventricular dysfunction. Journal of the American College of Cardiology. (2018) 71: 429-38.
(16)      Miyagawa S, Domae K, Yoshikawa Y, Fukushima S, Nakamura T, Saito A, Sakata Y, Hamada S, Toda K, and Pak K. Phase I clinical trial of autologous stem cell–sheet transplantation therapy for treating cardiomyopathy. Journal of the American Heart Association. (2017) 6: e003918.
(17)      Rossignol P, Hernandez AF, Solomon SD, and Zannad F. Heart failure drug treatment. The Lancet. (2019) 393: 1034-44.
(18)      Li Y, He L, Huang X, Bhaloo SI, Zhao H, Zhang S, Pu W, Tian X, Li Y, and Liu Q. Genetic lineage tracing of nonmyocyte population by dual recombinases. Circulation. (2018) 138: 793-805.
(19)      Ye L, D’Agostino G, Loo SJ, Wang CX, Su LP, Tan SH, Tee GZ, Pua CJ, Pena EM, and Cheng RB. Early regenerative capacity in the porcine heart. Circulation. (2018) 138: 2798-808.
(20)      Reimer KA, Lowe JE, Rasmussen MM, and Jennings RB. The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs. Circulation. (1977) 56: 786-94.
(21)      Tissier R, Ghaleh B, Cohen MV, Downey JM, and Berdeaux A. Myocardial protection with mild hypothermia. Cardiovasc Res. (2012) 94: 217-25.
(22)      Heusch G. Molecular Basis of Cardioprotection. Circulation Research. (2015) 116: 674-99.
(23)      Tsang A, Hausenloy DJ, Mocanu MM, and Yellon DM. Postconditioning: a form of "modified reperfusion" protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway. Circ Res. (2004) 95: 230-2.
(24)      Soetkamp D, Nguyen TT, Menazza S, Hirschhäuser C, Hendgen-Cotta UB, Rassaf T, Schlüter KD, Boengler K, Murphy E, and Schulz R. S-nitrosation of mitochondrial connexin 43 regulates mitochondrial function. Basic Research in Cardiology. (2014) 109: 433.
(25)      Leung MK and Irwin MG. Perioperative cardioprotection. F1000prime reports. (2013) 5:
(26)      Lionetti V and Barile L. Perioperative cardioprotection: back to bedside. Minerva anestesiologica. (2019)
(27)      Prabhu SD, Chandrasekar B, Murray DR, and Freeman GL. beta-adrenergic blockade in developing heart failure: effects on myocardial inflammatory cytokines, nitric oxide, and remodeling. Circulation. (2000) 101: 2103-9.
(28)      Gnecchi M, Danieli P, Malpasso G, and Ciuffreda MC. Paracrine Mechanisms of Mesenchymal Stem Cells in Tissue Repair. Methods Mol Biol. (2016) 1416: 123-46.
(29)      Heusch G. Critical Issues for the Translation of Cardioprotection. Circulation Research. (2017) 120: 1477-86.
(30)      Zimmermann W-H, Melnychenko I, Wasmeier G, Didié M, Naito H, Nixdorff U, Hess A, Budinsky L, Brune K, and Michaelis B. Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nature medicine. (2006) 12: 452.
(31)      O'Neill HS, O'Sullivan J, Porteous N, Ruiz‐Hernandez E, Kelly HM, O'Brien FJ, and Duffy GP. A collagen cardiac patch incorporating alginate microparticles permits the controlled release of hepatocyte growth factor and insulin‐like growth factor‐1 to enhance cardiac stem cell migration and proliferation. Journal of tissue engineering and regenerative medicine. (2018) 12: e384-e94.
(32)      Xiong Q, Hill KL, Li Q, Suntharalingam P, Mansoor A, Wang X, Jameel MN, Zhang P, Swingen C, Kaufman DS, and Zhang J. A fibrin patch-based enhanced delivery of human embryonic stem cell-derived vascular cell transplantation in a porcine model of postinfarction left ventricular remodeling. Stem Cells. (2011) 29: 367-75.
(33)      Idrees H, Zaidi SZJ, Sabir A, Khan RU, Zhang X, and Hassan SU. A Review of Biodegradable Natural Polymer-Based Nanoparticles for Drug Delivery Applications. Nanomaterials (Basel). (2020) 10:
(34)      Jiao Y, Li C, Liu L, Wang F, Liu X, Mao J, and Wang L. Construction and application of textile-based tissue engineering scaffolds: a review. Biomater Sci. (2020) 8: 3574-600.
(35)      Sell SA, McClure MJ, Garg K, Wolfe PS, and Bowlin GL. Electrospinning of collagen/biopolymers for regenerative medicine and cardiovascular tissue engineering. Advanced drug delivery reviews. (2009) 61: 1007-19.
(36)      Norahan MH, Amroon M, Ghahremanzadeh R, Mahmoodi M, and Baheiraei N. Electroactive graphene oxide‐incorporated collagen assisting vascularization for cardiac tissue engineering. Journal of Biomedical Materials Research Part A. (2019) 107: 204-19.
(37)      Qu H, Xie B-d, Wu J, Lv B, Chuai J-b, Li J-z, Cai J, Wu H, Jiang S-l, and Leng X-p. Improved left ventricular aneurysm repair with cell-and cytokine-seeded collagen patches. Stem cells international. (2018) 2018:
(38)      Lee AS, Inayathullah M, Lijkwan MA, Zhao X, Sun W, Park S, Hong WX, Parekh MB, Malkovskiy AV, and Lau E. Prolonged survival of transplanted stem cells after ischaemic injury via the slow release of pro-survival peptides from a collagen matrix. Nature biomedical engineering. (2018) 2: 104.
(39)      Sherrell PC, Cieślar‐Pobuda A, Ejneby MS, Sammalisto L, Gelmi A, de Muinck E, Brask J, Łos MJ, and Rafat M. Rational design of a conductive collagen heart patch. Macromolecular bioscience. (2017) 17: 1600446.
(40)      Kitsara M, Joanne P, Boitard SE, Ben Dhiab I, Poinard B, Menasché P, Gagnieu C, Forest P, Agbulut O, and Chen Y. Fabrication of cardiac patch by using electrospun collagen fibers. Microelectronic Engineering. (2015) 144: 46-50.
(41)      Hosoyama K and Ahumada M. Nanoengineered Electroconductive Collagen-Based Cardiac Patch for Infarcted Myocardium Repair. (2018) 10: 44668-77.
(42)      Ott HC, Matthiesen TS, Goh S-K, Black LD, Kren SM, Netoff TI, and Taylor DA. Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart. Nature medicine. (2008) 14: 213-21.
(43)      Weymann A, Patil NP, Sabashnikov A, Jungebluth P, Korkmaz S, Li S, Veres G, Soos P, Ishtok R, and Chaimow N. Bioartificial heart: a human-sized porcine model–the way ahead. PLoS One. (2014) 9: e111591.
(44)      Sanchez PL, Fernández-Santos ME, Costanza S, Climent AM, Moscoso I, Gonzalez-Nicolas MA, Sanz-Ruiz R, Rodríguez H, Kren SM, and Garrido G. Acellular human heart matrix: a critical step toward whole heart grafts. Biomaterials. (2015) 61: 279-89.
(45)      Sarig U, Au-Yeung GC, Wang Y, Bronshtein T, Dahan N, Boey FY, Venkatraman SS, and Machluf M. Thick acellular heart extracellular matrix with inherent vasculature: a potential platform for myocardial tissue regeneration. Tissue Engineering Part A. (2012) 18: 2125-37.
(46)      Hong X, Yuan Y, Sun X, Zhou M, Guo G, Zhang Q, Hescheler J, and Xi J. Skeletal extracellular matrix supports cardiac differentiation of embryonic stem cells: a potential scaffold for engineered cardiac tissue. Cellular Physiology and Biochemistry. (2018) 45: 319-31.
(47)      Oberwallner B, Brodarac A, Anić P, Šarić T, Wassilew K, Neef K, Choi Y-H, and Stamm C. Human cardiac extracellular matrix supports myocardial lineage commitment of pluripotent stem cells. European Journal of Cardio-Thoracic Surgery. (2015) 47: 416-25.
(48)      Cutts J, Nikkhah M, and Brafman DA. Biomaterial Approaches for Stem Cell-Based Myocardial Tissue Engineering: Supplementary Issue: Stem Cell Biology. Biomarker insights. (2015) 10: BMI. S20313.
(49)      Scarritt ME, Pashos NC, and Bunnell BA. A review of cellularization strategies for tissue engineering of whole organs. Frontiers in bioengineering and biotechnology. (2015) 3: 43.
(50)      Abdou ES, Nagy KS, and Elsabee MZ. Extraction and characterization of chitin and chitosan from local sources. Bioresource Technology. (2008) 99: 1359-67.
(51)      Liu N, Chen J, Zhuang J, and Zhu P. Fabrication of engineered nanoparticles on biological macromolecular (PEGylated chitosan) composite for bio-active hydrogel system in cardiac repair applications. International Journal of Biological Macromolecules. (2018) 117: 553-8.
(52)      Balasubramanian P, Prabhakaran MP, Kai D, and Ramakrishna S. Human cardiomyocyte interaction with electrospun fibrinogen/gelatin nanofibers for myocardial regeneration. J Biomater Sci Polym Ed. (2013) 24: 1660-75.
(53)      Ravichandran R, Venugopal JR, Sundarrajan S, Mukherjee S, Sridhar R, and Ramakrishna S. Expression of cardiac proteins in neonatal cardiomyocytes on PGS/fibrinogen core/shell substrate for Cardiac tissue engineering. Int J Cardiol. (2013) 167: 1461-8.
(54)      Ravichandran R, Venugopal JR, Mukherjee S, Sundarrajan S, and Ramakrishna S. Elastomeric core/shell nanofibrous cardiac patch as a biomimetic support for infarcted porcine myocardium. Tissue Eng Part A. (2015) 21: 1288-98.
(55)      Xiong Q, Ye L, Zhang P, Lepley M, Tian J, Li J, Zhang L, Swingen C, Vaughan JT, Kaufman DS, and Zhang J. Functional consequences of human induced pluripotent stem cell therapy: myocardial ATP turnover rate in the in vivo swine heart with postinfarction remodeling. Circulation. (2013) 127: 997-1008.
(56)      Zhang J. Engineered Tissue Patch for Cardiac Cell Therapy. Current treatment options in cardiovascular medicine. (2015) 17: 399-.
(57)      Chantawong P, Tanaka T, Uemura A, Shimada K, Higuchi A, Tajiri H, Sakura K, Murakami T, Nakazawa Y, and Tanaka R. Silk fibroin-Pellethane® cardiovascular patches: Effect of silk fibroin concentration on vascular remodeling in rat model. Journal of Materials Science: Materials in Medicine. (2017) 28: 191.
(58)      Yang M-C, Wang S-S, Chou N-K, Chi N-H, Huang Y-Y, Chang Y-L, Shieh M-J, and Chung T-W. The cardiomyogenic differentiation of rat mesenchymal stem cells on silk fibroin–polysaccharide cardiac patches in vitro. Biomaterials. (2009) 30: 3757-65.
(59)      Chi N-H, Yang M-C, Chung T-W, Chen J-Y, Chou N-K, and Wang S-S. Cardiac repair achieved by bone marrow mesenchymal stem cells/silk fibroin/hyaluronic acid patches in a rat of myocardial infarction model. Biomaterials. (2012) 33: 5541-51.
(60)      Patra C, Talukdar S, Novoyatleva T, Velagala SR, Mühlfeld C, Kundu B, Kundu SC, and Engel FB. Silk protein fibroin from Antheraea mylitta for cardiac tissue engineering. Biomaterials. (2012) 33: 2673-80.
(61)      Chi N-H, Yang M-C, Chung T-W, Chou N-K, and Wang S-S. Cardiac repair using chitosan-hyaluronan/silk fibroin patches in a rat heart model with myocardial infarction. Carbohydrate polymers. (2013) 92: 591-7.
(62)      Stoppel WL, Hu D, Domian IJ, Kaplan DL, and Black III LD. Anisotropic silk biomaterials containing cardiac extracellular matrix for cardiac tissue engineering. Biomedical materials. (2015) 10: 034105.
(63)      Malki M, Fleischer S, Shapira A, and Dvir T. Gold nanorod-based engineered cardiac patch for suture-free engraftment by near IR. Nano letters. (2018) 18: 4069-73.
(64)      Fleischer S, Shapira A, Feiner R, and Dvir T. Modular assembly of thick multifunctional cardiac patches. Proceedings of the National Academy of Sciences. (2017) 114: 1898-903.
(65)      Fleischer S, Shapira A, Regev O, Nseir N, Zussman E, and Dvir T. Albumin fiber scaffolds for engineering functional cardiac tissues. Biotechnology and bioengineering. (2014) 111: 1246-57.
(66)      Feiner R, Fleischer S, Shapira A, Kalish O, and Dvir T. Multifunctional degradable electronic scaffolds for cardiac tissue engineering. Journal of controlled release. (2018) 281: 189-95.
(67)      Yoon SJ, Fang YH, Lim CH, Kim BS, Son HS, Park Y, and Sun K. Regeneration of ischemic heart using hyaluronic acid‐based injectable hydrogel. Journal of Biomedical Materials Research Part B: Applied Biomaterials. (2009) 91: 163-71.
(68)      Dahlmann J, Krause A, Möller L, Kensah G, Möwes M, Diekmann A, Martin U, Kirschning A, Gruh I, and Dräger G. Fully defined in situ cross-linkable alginate and hyaluronic acid hydrogels for myocardial tissue engineering. Biomaterials. (2013) 34: 940-51.
(69)      Gaetani R, Feyen DA, Verhage V, Slaats R, Messina E, Christman KL, Giacomello A, Doevendans PA, and Sluijter JP. Epicardial application of cardiac progenitor cells in a 3D-printed gelatin/hyaluronic acid patch preserves cardiac function after myocardial infarction. Biomaterials. (2015) 61: 339-48.
(70)      Ceccaldi C, Bushkalova R, Alfarano C, Lairez O, Calise D, Bourin P, Frugier C, Rouzaud-Laborde C, Cussac D, and Parini A. Evaluation of polyelectrolyte complex-based scaffolds for mesenchymal stem cell therapy in cardiac ischemia treatment. Acta Biomaterialia. (2014) 10: 901-11.
(71)      Liu Y, Xu Y, Wang Z, Wen D, Zhang W, Schmull S, Li H, Chen Y, and Xue S. Electrospun nanofibrous sheets of collagen/elastin/polycaprolactone improve cardiac repair after myocardial infarction. American journal of translational research. (2016) 8: 1678-94.
(72)      Heydarkhan-Hagvall S, Schenke-Layland K, Dhanasopon AP, Rofail F, Smith H, Wu BM, Shemin R, Beygui RE, and MacLellan WR. Three-dimensional electrospun ECM-based hybrid scaffolds for cardiovascular tissue engineering. Biomaterials. (2008) 29: 2907-14.
(73)      Yeo GC, Mithieux SM, and Weiss AS. The elastin matrix in tissue engineering and regeneration. Current Opinion in Biomedical Engineering. (2018) 6: 27-32.
(74)      Kaiser NJ and Coulombe KL. Physiologically inspired cardiac scaffolds for tailored in vivo function and heart regeneration. Biomedical Materials. (2015) 10: 034003.
(75)      Shin M, Ishii O, Sueda T, and Vacanti J. Contractile cardiac grafts using a novel nanofibrous mesh. Biomaterials. (2004) 25: 3717-23.
(76)      Heydarkhan-Hagvall S, Schenke-Layland K, Dhanasopon AP, Rofail F, Smith H, Wu BM, Shemin R, Beygui RE, and MacLellan WR. Three-dimensional electrospun ECM-based hybrid scaffolds for cardiovascular tissue engineering. Biomaterials. (2008) 29: 2907-14.
(77)      Pushp P, Ferreira FC, Cabral JMS, and Gupta MK. Improved survival of cardiac cells on surface modified electrospun nanofibers. Polymer Science, Series A. (2017) 59: 515-23.
(78)      Guex A, Frobert A, Valentin J, Fortunato G, Hegemann D, Cook S, Carrel T, Tevaearai H, and Giraud M-N. Plasma-functionalized electrospun matrix for biograft development and cardiac function stabilization. Acta biomaterialia. (2014) 10: 2996-3006.
(79)      Srinivasa Reddy C, Reddy Venugopal J, Ramakrishna S, and Zussman E. Polycaprolactone/oligomer compound scaffolds for cardiac tissue engineering. Journal of Biomedical Materials Research Part A. (2014) 102: 3713-25.
(80)      Rai R, Tallawi M, Frati C, Falco A, Gervasi A, Quaini F, Roether JA, Hochburger T, Schubert DW, and Seik L. Bioactive electrospun fibers of poly (glycerol sebacate) and poly (ε‐caprolactone) for cardiac patch application. Advanced healthcare materials. (2015) 4: 2012-25.
(81)      Constantinides C, Basnett P, Lukasiewicz B, Carnicer R, Swider E, Majid QA, Srinivas M, Carr CA, and Roy I. In Vivo Tracking and 1H/19F Magnetic Resonance Imaging of Biodegradable Polyhydroxyalkanoate/Polycaprolactone Blend Scaffolds Seeded with Labeled Cardiac Stem Cells. ACS applied materials & interfaces. (2018) 10: 25056-68.
(82)      Lo HY, Huang AL, Lee PC, Chung TW, and Wang SS. Morphological transformation of h BMSC from 2 D monolayer to 3 D microtissue on low‐crystallinity SF‐PCL patch with promotion of cardiomyogenesis. Journal of tissue engineering and regenerative medicine. (2018) 12: e1852-e64.
(83)      Asadpour S, Yeganeh H, Ai J, Kargozar S, Rashtbar M, Seifalian A, and Ghanbari H. Polyurethane-Polycaprolactone Blend Patches: Scaffold Characterization and Cardiomyoblast Adhesion, Proliferation, and Function. ACS Biomaterials Science & Engineering. (2018) 4: 4299-310.
(84)      Sridhar S, Venugopal JR, Sridhar R, and Ramakrishna S. Cardiogenic differentiation of mesenchymal stem cells with gold nanoparticle loaded functionalized nanofibers. Colloids and Surfaces B: Biointerfaces. (2015) 134: 346-54.
(85)      Spearman BS, Hodge AJ, Porter JL, Hardy JG, Davis ZD, Xu T, Zhang X, Schmidt CE, Hamilton MC, and Lipke EA. Conductive interpenetrating networks of polypyrrole and polycaprolactone encourage electrophysiological development of cardiac cells. Acta biomaterialia. (2015) 28: 109-20.
(86)      Gouveia PJ, Rosa S, Ricotti L, Abecasis B, Almeida H, Monteiro L, Nunes J, Carvalho FS, Serra M, and Luchkin S. Flexible nanofilms coated with aligned piezoelectric microfibers preserve the contractility of cardiomyocytes. Biomaterials. (2017) 139: 213-28.
(87)      Mehdikhani M and Ghaziof S. Electrically conductive poly-∊-caprolactone/polyethylene glycol/multi-wall carbon nanotube nanocomposite scaffolds coated with fibrin glue for myocardial tissue engineering. Applied Physics A: Materials Science & Processing. (2018) 124:
(88)      Liu Q, Tian S, Zhao C, Chen X, Lei I, Wang Z, and Ma PX. Porous nanofibrous poly (L-lactic acid) scaffolds supporting cardiovascular progenitor cells for cardiac tissue engineering. Acta biomaterialia. (2015) 26: 105-14.
(89)      Bertuoli PT, Ordoño Js, Armelin E, Pérez-Amodio S, Baldissera AF, Ferreira CA, Puiggalí J, Engel E, del Valle LJ, and Alemán C. Electrospun Conducting and Biocompatible Uniaxial and Core–Shell Fibers Having Poly (lactic acid), Poly (ethylene glycol), and Polyaniline for Cardiac Tissue Engineering. ACS Omega. (2019) 4: 3660-72.
(90)      Chung H-J, Kim J-T, Kim H-J, Kyung H-W, Katila P, Lee J-H, Yang T-H, Yang Y-I, and Lee S-J. Epicardial delivery of VEGF and cardiac stem cells guided by 3-dimensional PLLA mat enhancing cardiac regeneration and angiogenesis in acute myocardial infarction. Journal of controlled release. (2015) 205: 218-30.
(91)      Spadaccio C, Nappi F, De Marco F, Sedati P, Taffon C, Nenna A, Crescenzi A, Chello M, Trombetta M, and Gambardella I. Implantation of a poly-L-lactide GCSF-functionalized scaffold in a model of chronic myocardial infarction. Journal of cardiovascular translational research. (2017) 10: 47-65.
(92)      Liu Y, Wang S, and Zhang R. Composite poly (lactic acid)/chitosan nanofibrous scaffolds for cardiac tissue engineering. International journal of biological macromolecules. (2017) 103: 1130-7.
(93)      Wang L, Wu Y, Hu T, Guo B, and Ma PX. Electrospun conductive nanofibrous scaffolds for engineering cardiac tissue and 3D bioactuators. Acta biomaterialia. (2017) 59: 68-81.
(94)      Aghdam RM, Shakhesi S, Najarian S, Mohammadi MM, Ahmadi Tafti SH, and Mirzadeh H. Fabrication of a nanofibrous scaffold for the in vitro culture of cardiac progenitor cells for myocardial regeneration. International Journal of Polymeric Materials and Polymeric Biomaterials. (2014) 63: 229-39.
(95)      Hosseinkhani H, Hosseinkhani M, Hattori S, Matsuoka R, and Kawaguchi N. Micro and nano‐scale in vitro 3D culture system for cardiac stem cells. Journal of Biomedical Materials Research Part A: An Official Journal of The Society for Biomaterials, The Japanese Society for Biomaterials, and The Australian Society for Biomaterials and the Korean Society for Biomaterials. (2010) 94: 1-8.
(96)      Nazeri N, Derakhshan MA, Faridi-Majidi R, and Ghanbari H. Novel electro-conductive nanocomposites based on electrospun PLGA/CNT for biomedical applications. Journal of Materials Science: Materials in Medicine. (2018) 29: 168.
(97)      Nazeri N, Tajerian R, Arabpour Z, Hadjighassem MR, Gheibi N, Manouchehrabadi M, and Ghanbari H. Bioinspired immobilization of carbon nanotubes on scaffolds for nerve regeneration. Bioinspired, Biomimetic and Nanobiomaterials. (2019) 1-8.
(98)      Cristallini C, Cibrario Rocchietti E, Gagliardi M, Mortati L, Saviozzi S, Bellotti E, Turinetto V, Sassi MP, Barbani N, and Giachino C. Micro-and macrostructured PLGA/Gelatin scaffolds promote early cardiogenic commitment of human mesenchymal stem cells in vitro. Stem cells international. (2016) 2016:
(99)      Chen Y, Wang J, Shen B, Chan CW, Wang C, Zhao Y, Chan HN, Tian Q, Chen Y, and Yao C. Engineering a freestanding biomimetic cardiac patch using biodegradable poly (lactic‐co‐glycolic acid)(PLGA) and human embryonic stem cell‐derived ventricular cardiomyocytes (hESC‐VCMs). Macromolecular bioscience. (2015) 15: 426-36.
(100)    Cristallini C, Cibrario Rocchietti E, Gagliardi M, Mortati L, Saviozzi S, Bellotti E, Turinetto V, Sassi MP, Barbani N, and Giachino C. Micro- and Macrostructured PLGA/Gelatin Scaffolds Promote Early Cardiogenic Commitment of Human Mesenchymal Stem Cells In Vitro. Stem Cells Int. (2016) 2016: 7176154.
(101)    Khan M, Xu Y, Hua S, Johnson J, Belevych A, Janssen PM, Gyorke S, Guan J, and Angelos MG. Evaluation of changes in morphology and function of human induced pluripotent stem cell derived cardiomyocytes (HiPSC-CMs) cultured on an aligned-nanofiber cardiac patch. PloS one. (2015) 10: e0126338.
(102)    Yu J, Lee A-R, Lin W-H, Lin C-W, Wu Y-K, and Tsai W-B. Electrospun PLGA fibers incorporated with functionalized biomolecules for cardiac tissue engineering. Tissue Engineering Part A. (2014) 20: 1896-907.
(103)    Hashizume R, Hong Y, Takanari K, Fujimoto KL, Tobita K, and Wagner WR. The effect of polymer degradation time on functional outcomes of temporary elastic patch support in ischemic cardiomyopathy. Biomaterials. (2013) 34: 7353-63.
(104)    Kim HN, Jiao A, Hwang NS, Kim MS, Kim D-H, and Suh K-Y. Nanotopography-guided tissue engineering and regenerative medicine. Advanced drug delivery reviews. (2013) 65: 536-58.
(105)    Kim D-H, Lipke EA, Kim P, Cheong R, Thompson S, Delannoy M, Suh K-Y, Tung L, and Levchenko A. Nanoscale cues regulate the structure and function of macroscopic cardiac tissue constructs. Proceedings of the National Academy of Sciences. (2010) 107: 565-70.
(106)    Tsui JH, Ostrovsky-Snider NA, Yama DM, Donohue JD, Choi JS, Chavanachat R, Larson JD, Murphy AR, and Kim D-H. Conductive silk–polypyrrole composite scaffolds with bioinspired nanotopographic cues for cardiac tissue engineering. Journal of Materials Chemistry B. (2018) 6: 7185-96.
(107)    Ghosh LD, Jain A, Sundaresan NR, and Chatterjee K. Elucidating molecular events underlying topography mediated cardiomyogenesis of stem cells on 3D nanofibrous scaffolds. Materials Science and Engineering: C. (2018) 88: 104-14.
(108)    Fleischer S, Feiner R, Shapira A, Ji J, Sui X, Wagner HD, and Dvir T. Spring-like fibers for cardiac tissue engineering. Biomaterials. (2013) 34: 8599-606.
(109)    Stoppel WL, Kaplan DL, and Black III LD. Electrical and mechanical stimulation of cardiac cells and tissue constructs. Advanced drug delivery reviews. (2016) 96: 135-55.
(110)    Hernández D, Millard R, Sivakumaran P, Wong RC, Crombie DE, Hewitt AW, Liang H, Hung SS, Pébay A, and Shepherd RK. Electrical stimulation promotes cardiac differentiation of human induced pluripotent stem cells. Stem cells international. (2016) 2016:
(111)    Pavesi A, Soncini M, Zamperone A, Pietronave S, Medico E, Redaelli A, Prat M, and Fiore GB. Electrical conditioning of adipose‐derived stem cells in a multi‐chamber culture platform. Biotechnology and bioengineering. (2014) 111: 1452-63.
(112)    Mooney E, Mackle JN, Blond DJ-P, O'Cearbhaill E, Shaw G, Blau WJ, Barry FP, Barron V, and Murphy JM. The electrical stimulation of carbon nanotubes to provide a cardiomimetic cue to MSCs. Biomaterials. (2012) 33: 6132-9.
(113)    Genovese JA, Spadaccio C, Chachques E, Schussler O, Carpentier A, Chachques JC, and Patel AN. Cardiac pre-differentiation of human mesenchymal stem cells by electrostimulation. Front Biosci. (2009) 14: 2996-3002.
(114)    Stone H, Lin S, and Mequanint K. Preparation and characterization of electrospun rGO-poly (ester amide) conductive scaffolds. Materials Science and Engineering: C. (2019) 98: 324-32.
(115)    Serena E, Figallo E, Tandon N, Cannizzaro C, Gerecht S, Elvassore N, and Vunjak-Novakovic G. Electrical stimulation of human embryonic stem cells: cardiac differentiation and the generation of reactive oxygen species. Experimental cell research. (2009) 315: 3611-9.
(116)    Chan Y-C, Ting S, Lee Y-K, Ng K-M, Zhang J, Chen Z, Siu C-W, Oh SK, and Tse H-F. Electrical stimulation promotes maturation of cardiomyocytes derived from human embryonic stem cells. Journal of cardiovascular translational research. (2013) 6: 989-99.
(117)    Genovese JA, Spadaccio C, Langer J, Habe J, Jackson J, and Patel AN. Electrostimulation induces cardiomyocyte predifferentiation of fibroblasts. Biochemical and biophysical research communications. (2008) 370: 450-5.
(118)    Pietronave S, Zamperone A, Oltolina F, Colangelo D, Follenzi A, Novelli E, Diena M, Pavesi A, Consolo F, and Fiore GB. Monophasic and biphasic electrical stimulation induces a precardiac differentiation in progenitor cells isolated from human heart. Stem cells and development. (2013) 23: 888-98.
(119)    Llucià-Valldeperas A, Sanchez B, Soler-Botija C, Gálvez-Montón C, Roura S, Prat-Vidal C, Perea-Gil I, Rosell-Ferrer J, Bragos R, and Bayes-Genis A. Physiological conditioning by electric field stimulation promotes cardiomyogenic gene expression in human cardiomyocyte progenitor cells. Stem cell research & therapy. (2014) 5: 93.
(120)    Zhang Y, Fan W, Wang K, Wei H, Zhang R, and Wu Y. Novel preparation of Au nanoparticles loaded Laponite nanoparticles/ECM injectable hydrogel on cardiac differentiation of resident cardiac stem cells to cardiomyocytes. Journal of Photochemistry and Photobiology B: Biology. (2019) 192: 49-54.
(121)    Kalishwaralal K, Jeyabharathi S, Sundar K, Selvamani S, Prasanna M, and Muthukumaran A. A novel biocompatible chitosan–Selenium nanoparticles (SeNPs) film with electrical conductivity for cardiac tissue engineering application. Materials Science and Engineering: C. (2018) 92: 151-60.
(122)    Baei P, Jalili-Firoozinezhad S, Rajabi-Zeleti S, Tafazzoli-Shadpour M, Baharvand H, and Aghdami N. Electrically conductive gold nanoparticle-chitosan thermosensitive hydrogels for cardiac tissue engineering. Materials Science and Engineering: C. (2016) 63: 131-41.
(123)    Ye G and Qiu X. Conductive biomaterials in cardiac tissue engineering. Biotarget. (2017) 1:
(124)    Cabiati M, Vozzi F, Gemma F, Montemurro F, De Maria C, Vozzi G, Domenici C, and Del Ry S. Cardiac tissue regeneration: A preliminary study on carbon‐based nanotubes gelatin scaffold. Journal of Biomedical Materials Research Part B: Applied Biomaterials. (2018) 106: 2750-62.
(125)    Shin SR, Jung SM, Zalabany M, Kim K, Zorlutuna P, Kim SB, Nikkhah M, Khabiry M, Azize M, and Kong J. Carbon-nanotube-embedded hydrogel sheets for engineering cardiac constructs and bioactuators. ACS nano. (2013) 7: 2369-80.
(126)    Hitscherich P, Aphale A, Gordan R, Whitaker R, Singh P, Xie Lh, Patra P, and Lee EJ. Electroactive graphene composite scaffolds for cardiac tissue engineering. Journal of Biomedical Materials Research Part A. (2018) 106: 2923-33.
(127)    Yang B, Yao F, Hao T, Fang W, Ye L, Zhang Y, Wang Y, Li J, and Wang C. Development of Electrically Conductive Double‐Network Hydrogels via One‐Step Facile Strategy for Cardiac Tissue Engineering. Advanced healthcare materials. (2016) 5: 474-88.
(128)    Kharaziha M, Memic A, Akbari M, Brafman DA, and Nikkhah M. Nano‐enabled approaches for stem cell‐based cardiac tissue engineering. Advanced healthcare materials. (2016) 5: 1533-53.
(129)    Thrivikraman G, Madras G, and Basu B. Electrically driven intracellular and extracellular nanomanipulators evoke neurogenic/cardiomyogenic differentiation in human mesenchymal stem cells. Biomaterials. (2016) 77: 26-43.
(130)    Yao Y, Liao W, Yu R, Du Y, Zhang T, and Peng Q. Potentials of combining nanomaterials and stem cell therapy in myocardial repair. Nanomedicine. (2018) 13: 1623-38.
(131)    Mueller P, Lemcke H, and David R. Stem cell therapy in heart diseases–cell types, mechanisms and improvement strategies. Cellular Physiology and Biochemistry. (2018) 48: 2607-55.
(132)    Bellamy V, Vanneaux V, Bel A, Nemetalla H, Boitard SE, Farouz Y, Joanne P, Perier M-C, Robidel E, and Mandet C. Long-term functional benefits of human embryonic stem cell-derived cardiac progenitors embedded into a fibrin scaffold. The Journal of Heart and Lung Transplantation. (2015) 34: 1198-207.
(133)    Ke Q, Yang Y, Rana JS, Chen Y, Morgan JP, and Xiao Y. Embryonic stem cells cultured in biodegradable scaffold repair infarcted myocardium in mice. ACTA PHYSIOLOGICA SINICA-CHINESE EDITION-. (2005) 57: 673.
(134)    Lu W-N, Lü S-H, Wang H-B, Li D-X, Duan C-M, Liu Z-Q, Hao T, He W-J, Xu B, and Fu Q. Functional improvement of infarcted heart by co-injection of embryonic stem cells with temperature-responsive chitosan hydrogel. Tissue Engineering Part A. (2008) 15: 1437-47.
(135)    Reubinoff BE, Pera MF, Fong C-Y, Trounson A, and Bongso A. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nature biotechnology. (2000) 18: 399-404.
(136)    Singla DK and Sobel BE. Enhancement by growth factors of cardiac myocyte differentiation from embryonic stem cells: a promising foundation for cardiac regeneration. Biochemical and biophysical research communications. (2005) 335: 637-42.
(137)    Gorabi AM, Tafti SHA, Soleimani M, Panahi Y, and Sahebkar A. Cells, scaffolds and their interactions in myocardial tissue regeneration. Journal of cellular biochemistry. (2017) 118: 2454-62.
(138)    Zhang Y, Wang D, Chen M, Yang B, Zhang F, and Cao K. Intramyocardial transplantation of undifferentiated rat induced pluripotent stem cells causes tumorigenesis in the heart. PloS one. (2011) 6: e19012.
(139)    Lalit PA, Hei DJ, Raval AN, and Kamp TJ. Induced Pluripotent Stem Cells for Post–Myocardial Infarction Repair: Remarkable Opportunities and Challenges. Circulation research. (2014) 114: 1328-45.
(140)    Ahmed RP, Ashraf M, Buccini S, Shujia J, and Haider HK. Cardiac tumorgenic potential of induced pluripotent stem cells in an immunocompetent host with myocardial infarction. Regenerative medicine. (2011) 6: 171-8.
(141)    Wu DC, Boyd AS, and Wood KJ. Embryonic stem cells and their differentiated derivatives have a fragile immune privilege but still represent novel targets of immune attack. Stem Cells. (2008) 26: 1939-50.
(142)    Wang X, Lu M, Tian X, Ren Y, Li Y, Xiang M, and Chen S. Diminished expression of major histocompatibility complex facilitates the use of human induced pluripotent stem cells in monkey. (2020) 11: 334.
(143)    Romagnuolo R, Masoudpour H, Porta-Sánchez A, Qiang B, Barry J, Laskary A, Qi X, Massé S, Magtibay K, Kawajiri H, Wu J, Valdman Sadikov T, Rothberg J, Panchalingam KM, Titus E, Li R-K, Zandstra PW, Wright GA, Nanthakumar K, Ghugre NR, Keller G, and Laflamme MA. Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate the Infarcted Pig Heart but Induce Ventricular Tachyarrhythmias. Stem Cell Reports. (2019) 12: 967-81.
(144)    Paci M, Penttinen K, Pekkanen-Mattila M, and Koivumäki JT. Arrhythmia Mechanisms in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. J Cardiovasc Pharmacol. (2020) 77: 300-16.
(145)    Mummery CL, Zhang J, Ng ES, Elliott DA, Elefanty AG, and Kamp TJ. Differentiation of human embryonic stem cells and induced pluripotent stem cells to cardiomyocytes: a methods overview. Circ Res. (2012) 111: 344-58.
(146)    Karbassi E, Fenix A, Marchiano S, Muraoka N, Nakamura K, Yang X, and Murry CE. Cardiomyocyte maturation: advances in knowledge and implications for regenerative medicine. (2020) 17: 341-59.
(147)    Yang X, Pabon L, and Murry CE. Engineering adolescence: maturation of human pluripotent stem cell-derived cardiomyocytes. Circ Res. (2014) 114: 511-23.
(148)    Richards DJ, Tan Y, Coyle R, Li Y, Xu R, Yeung N, Parker A, Menick DR, Tian B, and Mei Y. Nanowires and Electrical Stimulation Synergistically Improve Functions of hiPSC Cardiac Spheroids. Nano Letters. (2016) 16: 4670-8.
(149)    Reinecke H, Zhang M, Bartosek T, and Murry CE. Survival, integration, and differentiation of cardiomyocyte grafts: a study in normal and injured rat hearts. Circulation. (1999) 100: 193-202.
(150)    Eschenhagen T, Bolli R, Braun T, Field LJ, Fleischmann BK, Frisén J, Giacca M, Hare JM, Houser S, and Lee RT. Cardiomyocyte regeneration: a consensus statement. Circulation. (2017) 136: 680-6.
(151)    Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabé-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, and Druid H. Evidence for cardiomyocyte renewal in humans. Science. (2009) 324: 98-102.
(152)    Smith AJ, Lewis FC, Aquila I, Waring CD, Nocera A, Agosti V, Nadal-Ginard B, Torella D, and Ellison GM. Isolation and characterization of resident endogenous c-Kit+ cardiac stem cells from the adult mouse and rat heart. Nat Protoc. (2014) 9: 1662-81.
(153)    Ellison GM, Vicinanza C, Smith AJ, Aquila I, Leone A, Waring CD, Henning BJ, Stirparo GG, Papait R, Scarfò M, Agosti V, Viglietto G, Condorelli G, Indolfi C, Ottolenghi S, Torella D, and Nadal-Ginard B. Adult c-kit(pos) cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair. Cell. (2013) 154: 827-42.
(154)    Hong KU, Guo Y, Li Q-H, Cao P, Al-Maqtari T, Vajravelu BN, Du J, Book MJ, Zhu X, and Nong Y. c-kit+ Cardiac stem cells alleviate post-myocardial infarction left ventricular dysfunction despite poor engraftment and negligible retention in the recipient heart. PloS one. (2014) 9: e96725.
(155)    Su T, Huang K, Daniele MA, Hensley MT, Young AT, Tang J, Allen TA, Vandergriff AC, Erb PD, and Ligler FS. Cardiac Stem Cell Patch Integrated with Microengineered Blood Vessels Promotes Cardiomyocyte Proliferation and Neovascularization after Acute Myocardial Infarction. ACS applied materials & interfaces. (2018) 10: 33088-96.
(156)    Zhang Z, Yang J, Yan W, Li Y, Shen Z, and Asahara T. Pretreatment of cardiac stem cells with exosomes derived from mesenchymal stem cells enhances myocardial repair. Journal of the American Heart Association. (2016) 5: e002856.
(157)    Mehryab F, Rabbani S, Shahhosseini S, Shekari F, Fatahi Y, Baharvand H, and Haeri A. Exosomes as a next-generation drug delivery system: An update on drug loading approaches, characterization, and clinical application challenges. Acta Biomater. (2020) 113: 42-62.
(158)    Mauretti A, Spaans S, Bax NA, Sahlgren C, and Bouten CV. Cardiac progenitor cells and the interplay with their microenvironment. Stem cells international. (2017) 2017:
(159)    Chong JJ, Forte E, and Harvey RP. Developmental origins and lineage descendants of endogenous adult cardiac progenitor cells. Stem cell research. (2014) 13: 592-614.
(160)    Van Berlo JH, Kanisicak O, Maillet M, Vagnozzi RJ, Karch J, Lin S-CJ, Middleton RC, Marbán E, and Molkentin JD. C-kit+ cells minimally contribute cardiomyocytes to the heart. Nature. (2014) 509: 337-41.
(161)    Vicinanza C, Aquila I, Scalise M, Cristiano F, Marino F, Cianflone E, Mancuso T, Marotta P, Sacco W, and Lewis FC. Adult cardiac stem cells are multipotent and robustly myogenic: c-kit expression is necessary but not sufficient for their identification. Cell Death & Differentiation. (2017) 24: 2101-16.
(162)    Torán JL, Aguilar S, López JA, Torroja C, Quintana JA, Santiago C, Abad JL, Gomes-Alves P, Gonzalez A, and Bernal JA. CXCL6 is an important paracrine factor in the pro-angiogenic human cardiac progenitor-like cell secretome. Scientific reports. (2017) 7: 1-14.
(163)    Martin CM, Meeson AP, Robertson SM, Hawke TJ, Richardson JA, Bates S, Goetsch SC, Gallardo TD, and Garry DJ. Persistent expression of the ATP-binding cassette transporter, Abcg2, identifies cardiac SP cells in the developing and adult heart. Developmental biology. (2004) 265: 262-75.
(164)    Matsuura K, Honda A, Nagai T, Fukushima N, Iwanaga K, Tokunaga M, Shimizu T, Okano T, Kasanuki H, and Hagiwara N. Transplantation of cardiac progenitor cells ameliorates cardiac dysfunction after myocardial infarction in mice. The Journal of clinical investigation. (2009) 119: 2204-17.
(165)    Barile L, Lionetti V, Cervio E, Matteucci M, Gherghiceanu M, Popescu LM, Torre T, Siclari F, Moccetti T, and Vassalli G. Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction. Cardiovascular research. (2014) 103: 530-41.
(166)    Hare JM, Fishman JE, Gerstenblith G, Velazquez DLD, Zambrano JP, Suncion VY, Tracy M, Ghersin E, Johnston PV, and Brinker JA. Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. Jama. (2012) 308: 2369-79.
(167)    Rabbani S, Soleimani M, Imani M, Sahebjam M, Ghiaseddin A, Nassiri SM, Majd Ardakani J, Tajik Rostami M, Jalali A, Mousanassab B, Kheradmandi M, and Ahmadi Tafti SH. Regenerating Heart Using a Novel Compound and Human Wharton Jelly Mesenchymal Stem Cells. Archives of Medical Research. (2017) 48: 228-37.
(168)    Rabbani S, Soleimani M, Sahebjam M, Imani M, Haeri A, Ghiaseddin A, Nassiri SM, Majd Ardakani J, Tajik Rostami M, Jalali A, and Ahmadi Tafti SH. Simultaneous Delivery of Wharton's Jelly Mesenchymal Stem Cells and Insulin-Like Growth Factor-1 in Acute Myocardial Infarction. Iranian journal of pharmaceutical research : IJPR. (2018) 17: 426-41.
(169)    Liu J, Hu Q, Wang Z, Xu C, Wang X, Gong G, Mansoor A, Lee J, Hou M, and Zeng L. Autologous stem cell transplantation for myocardial repair. American Journal of Physiology-Heart and Circulatory Physiology. (2004) 287: H501-H11.
(170)    Kai D, Wang Q-L, Wang H-J, Prabhakaran MP, Zhang Y, Tan Y-Z, and Ramakrishna S. Stem cell-loaded nanofibrous patch promotes the regeneration of infarcted myocardium with functional improvement in rat model. Acta biomaterialia. (2014) 10: 2727-38.
(171)    Godier-Furnémont AF, Martens TP, Koeckert MS, Wan L, Parks J, Arai K, Zhang G, Hudson B, Homma S, and Vunjak-Novakovic G. Composite scaffold provides a cell delivery platform for cardiovascular repair. Proceedings of the National Academy of Sciences. (2011) 108: 7974-9.
(172)    Menasché P, Hagège AA, Scorsin M, Pouzet B, Desnos M, Duboc D, Schwartz K, Vilquin J-T, and Marolleau J-P. Myoblast transplantation for heart failure. The Lancet. (2001) 357: 279-80.
(173)    Sawa Y, Yoshikawa Y, Toda K, Fukushima S, Yamazaki K, Ono M, Sakata Y, Hagiwara N, Kinugawa K, and Miyagawa S. Safety and efficacy of autologous skeletal myoblast sheets (TCD-51073) for the treatment of severe chronic heart failure due to ischemic heart disease. Circulation Journal. (2015) 79: 991-9.
(174)    Yoshikawa Y, Miyagawa S, Toda K, Saito A, Sakata Y, and Sawa Y. Myocardial regenerative therapy using a scaffold-free skeletal-muscle-derived cell sheet in patients with dilated cardiomyopathy even under a left ventricular assist device: a safety and feasibility study. Surgery today. (2018) 48: 200-10.
(175)    Komae H, Ono M, and Shimizu T. Cell Sheet-Based Vascularized Myocardial Tissue Fabrication. European Surgical Research. (2018) 59: 276-85.
(176)    Ishigami M, Masumoto H, Ikuno T, Aoki T, Kawatou M, Minakata K, Ikeda T, Sakata R, Yamashita JK, and Minatoya K. Human iPS cell-derived cardiac tissue sheets for functional restoration of infarcted porcine hearts. PloS one. (2018) 13: e0201650.
(177)    Kawamura M, Miyagawa S, Fukushima S, Saito A, Miki K, Funakoshi S, Yoshida Y, Yamanaka S, Shimizu T, and Okano T. Enhanced therapeutic effects of human iPS cell derived-cardiomyocyte by combined cell-sheets with omental flap technique in porcine ischemic cardiomyopathy model. Scientific reports. (2017) 7: 8824.
(178)    Addis RC, Ifkovits JL, Pinto F, Kellam LD, Esteso P, Rentschler S, Christoforou N, Epstein JA, and Gearhart JD. Optimization of direct fibroblast reprogramming to cardiomyocytes using calcium activity as a functional measure of success. J Mol Cell Cardiol. (2013) 60: 97-106.
(179)    Cahill TJ, Choudhury RP, and Riley PR. Heart regeneration and repair after myocardial infarction: translational opportunities for novel therapeutics. Nat Rev Drug Discov. (2017) 16: 699-717.
(180)    Lalit PA, Salick MR, Nelson DO, Squirrell JM, Shafer CM, Patel NG, Saeed I, Schmuck EG, Markandeya YS, Wong R, Lea MR, Eliceiri KW, Hacker TA, Crone WC, Kyba M, Garry DJ, Stewart R, Thomson JA, Downs KM, Lyons GE, and Kamp TJ. Lineage Reprogramming of Fibroblasts into Proliferative Induced Cardiac Progenitor Cells by Defined Factors. Cell Stem Cell. (2016) 18: 354-67.
(181)    Wada R, Muraoka N, Inagawa K, Yamakawa H, Miyamoto K, Sadahiro T, Umei T, Kaneda R, Suzuki T, Kamiya K, Tohyama S, Yuasa S, Kokaji K, Aeba R, Yozu R, Yamagishi H, Kitamura T, Fukuda K, and Ieda M. Induction of human cardiomyocyte-like cells from fibroblasts by defined factors. Proc Natl Acad Sci U S A. (2013) 110: 12667-72.
(182)    Kim TK, Sul JY, Peternko NB, Lee JH, Lee M, Patel VV, Kim J, and Eberwine JH. Transcriptome transfer provides a model for understanding the phenotype of cardiomyocytes. Proc Natl Acad Sci U S A. (2011) 108: 11918-23.
(183)    Mathur A, Loskill P, Shao K, Huebsch N, Hong S, Marcus SG, Marks N, Mandegar M, Conklin BR, Lee LP, and Healy KE. Human iPSC-based Cardiac Microphysiological System For Drug Screening Applications. Scientific Reports. (2015) 5: 8883.
(184)    Sidorov VY, Samson PC, Sidorova TN, Davidson JM, Lim CC, and Wikswo JP. I-Wire Heart-on-a-Chip I: Three-dimensional cardiac tissue constructs for physiology and pharmacology. Acta Biomater. (2017) 48: 68-78.
(185)    Zhuang J, Yamada KA, Saffitz JE, and Kléber AG. Pulsatile Stretch Remodels Cell-to-Cell Communication in Cultured Myocytes. Circulation Research. (2000) 87: 316-22.
(186)    Schroer AK, Shotwell MS, Sidorov VY, Wikswo JP, and Merryman WD. I-Wire Heart-on-a-Chip II: Biomechanical analysis of contractile, three-dimensional cardiomyocyte tissue constructs. Acta Biomater. (2017) 48: 79-87.
(187)    Müller P, Beltrami AP, Cesselli D, Pfeiffer P, Kazakov A, and Böhm M. Myocardial regeneration by endogenous adult progenitor cells. Journal of molecular and cellular cardiology. (2005) 39: 377-87.
(188)    Leri A, Kajstura J, and Anversa P. Cardiac stem cells and mechanisms of myocardial regeneration. Physiological reviews. (2005) 85: 1373-416.
(189)    Boehler RM, Graham JG, and Shea LD. Tissue engineering tools for modulation of the immune response. BioTechniques. (2011) 51: 239-54.
(190)    Burt HM and Hunter WL. Drug-eluting stents: A multidisciplinary success story. Advanced Drug Delivery Reviews. (2006) 58: 350-7.
(191)    Haeri A, Sadeghian S, Rabbani S, Anvari MS, Ghassemi S, Radfar F, and Dadashzadeh S. Effective attenuation of vascular restenosis following local delivery of chitosan decorated sirolimus liposomes. Carbohydr Polym. (2017) 157: 1461-9.
(192)    Haeri A, Sadeghian S, Rabbani S, Shirani S, Anvari MS, and Dadashzadeh S. Physicochemical characteristics of liposomes are decisive for their antirestenosis efficacy following local delivery. Nanomedicine (Lond). (2017) 12: 131-45.
(193)    Haeri A, Sadeghian S, Rabbani S, Anvari MS, Lavasanifar A, Amini M, and Dadashzadeh S. Sirolimus-loaded stealth colloidal systems attenuate neointimal hyperplasia after balloon injury: a comparison of phospholipid micelles and liposomes. Int J Pharm. (2013) 455: 320-30.
(194)    Haeri A, Sadeghian S, Rabbani S, Anvari MS, Erfan M, and Dadashzadeh S. PEGylated estradiol benzoate liposomes as a potential local vascular delivery system for treatment of restenosis. J Microencapsul. (2012) 29: 83-94.
(195)    Haeri A, Sadeghian S, Rabbani S, Anvari MS, Boroumand MA, and Dadashzadeh S. Use of remote film loading methodology to entrap sirolimus into liposomes: preparation, characterization and in vivo efficacy for treatment of restenosis. Int J Pharm. (2011) 414: 16-27.
(196)    Venkataraman L, Sivaraman B, Vaidya P, and Ramamurthi A. Nanoparticulate delivery of agents for induced elastogenesis in three-dimensional collagenous matrices. Journal of Tissue Engineering and Regenerative Medicine. (2016) 10: 1041-56.
(197)    Takahashi T, Lord B, Schulze PC, Fryer RM, Sarang SS, Gullans SR, and Lee RT. Ascorbic acid enhances differentiation of embryonic stem cells into cardiac myocytes. Circulation. (2003) 107: 1912-6.
(198)    Wu X, Ding S, Ding Q, Gray NS, and Schultz PG. Small molecules that induce cardiomyogenesis in embryonic stem cells. Journal of the American Chemical Society. (2004) 126: 1590-1.
(199)    Oh H, Bradfute SB, Gallardo TD, Nakamura T, Gaussin V, Mishina Y, Pocius J, Michael LH, Behringer RR, and Garry DJ. Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proceedings of the National Academy of Sciences. (2003) 100: 12313-8.
(200)    Hastings CL, Roche ET, Ruiz-Hernandez E, Schenke-Layland K, Walsh CJ, and Duffy GP. Drug and cell delivery for cardiac regeneration. Advanced Drug Delivery Reviews. (2015) 84: 85-106.
(201)    Theiss HD, Vallaster M, Rischpler C, Krieg L, Zaruba M-M, Brunner S, Vanchev Y, Fischer R, Gröbner M, Huber B, Wollenweber T, Assmann G, Mueller-Hoecker J, Hacker M, and Franz W-M. Dual stem cell therapy after myocardial infarction acts specifically by enhanced homing via the SDF-1/CXCR4 axis. Stem Cell Research. (2011) 7: 244-55.
(202)    Dong X-Q, Du Q, Yu W-H, Zhang Z-Y, Zhu Q, Che Z-H, Chen F, Wang H, and Chen J. Anti-inflammatory Effects of Oxymatrine Through Inhibition of Nuclear Factor–kappa B and Mitogen-activated Protein Kinase Activation in Lipopolysaccharide-induced BV2 Microglia Cells. Iranian Journal of Pharmaceutical Research. (2013) 12: 165-74.
(203)    Shahrasbi M, Azami Movahed M, Ghorban Dadras O, Daraei B, and Zarghi A. Design, Synthesis and Biological Evaluation of New Imidazo[2,1-b]Thiazole Derivatives as Selective COX-2 Inhibitors. Iranian journal of pharmaceutical research : IJPR. (2018) 17: 1288-96.
(204)    Murakoshi M, Saiki K, Urayama K, and Sato TN. An Anthelmintic Drug, Pyrvinium Pamoate, Thwarts Fibrosis and Ameliorates Myocardial Contractile Dysfunction in a Mouse Model of Myocardial Infarction. PLOS ONE. (2013) 8: e79374.
(205)    Sanada F, Kim J, Czarna A, Chan NYK, Signore S, Ogórek B, Isobe K, Wybieralska E, Borghetti G, Pesapane A, Sorrentino A, Mangano E, Cappetta D, Mangiaracina C, Ricciardi M, Cimini M, Ifedigbo E, Perrella MA, Goichberg P, Choi AM, Kajstura J, Hosoda T, Rota M, Anversa P, and Leri A. C-kit-positive cardiac stem cells nested in hypoxic niches are activated by stem cell factor reversing the aging myopathy. Circulation Research. (2014) 114: 41-55.
(206)    Plowright AT, Engkvist O, Gill A, Knerr L, and Wang Q-D. Heart Regeneration: Opportunities and Challenges for Drug Discovery with Novel Chemical and Therapeutic Methods or Agents. Angewandte Chemie International Edition. (2014) 53: 4056-75.
(207)    Segers VFM and Lee RT. Protein Therapeutics for Cardiac Regeneration after Myocardial Infarction. Journal of Cardiovascular Translational Research. (2010) 3: 469-77.
(208)    ebadi a, razzaghi asl N, Shahabipour S, and miri r. Ab-Initio and Conformational Analysis of a Potent VEGFR-2 Inhibitor: A Case Study on Motesanib. Iranian Journal of Pharmaceutical Research. (2014) 13: 405-15.
(209)    Darakhshan S, Bidmeshkipour A, Mansouri K, Saeid HM, and Ghanbari A. The Effects of Tamoxifen in Combination with Tranilast on CXCL12-CXCR4 Axis and Invasion in Breast Cancer Cell Lines. Iranian journal of pharmaceutical research : IJPR. (2014) 13: 683-93.
(210)    Segers VFM, Tokunou T, Higgins LJ, MacGillivray C, Gannon J, and Lee RT. Local Delivery of Protease-Resistant Stromal Cell Derived Factor-1 for Stem Cell Recruitment After Myocardial Infarction. Circulation. (2007) 116: 1683-92.
(211)    Jabbour A, Hayward CS, Keogh AM, Kotlyar E, McCrohon JA, England JF, Amor R, Liu X, Li XY, Zhou MD, Graham RM, and Macdonald PS. Parenteral administration of recombinant human neuregulin-1 to patients with stable chronic heart failure produces favourable acute and chronic haemodynamic responses. European Journal of Heart Failure. (2011) 13: 83-92.
(212)    Ortolon K. Rx battle. Tex Med. (2002) 98: 26-8.
(213)    Ranjbari J, Babaeipour V, Vahidi H, Moghimi H, Mofid M, Namvaran M, and Jafari S. Enhanced Production of Insulin-Like Growth Factor I Protein in Escherichia coli by optimization of five key factors. Iranian Journal of Pharmaceutical Research. (2015) 14: 907-17.
(214)    O'Sullivan JF, Leblond A-L, Kelly G, Kumar AHS, Metharom P, Büneker CK, Alizadeh-Vikali N, Hristova I, Hynes BG, O'Connor R, and Caplice NM. Potent Long-Term Cardioprotective Effects of Single Low-Dose Insulin-Like Growth Factor-1 Treatment Postmyocardial Infarction. Circulation: Cardiovascular Interventions. (2011) 4: 327-35.
(215)    Formiga FR, Pelacho B, Garbayo E, Imbuluzqueta I, Díaz-Herráez P, Abizanda G, Gavira JJ, Simón-Yarza T, Albiasu E, Tamayo E, Prósper F, and Blanco-Prieto MJ. Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration. Journal of Controlled Release. (2014) 173: 132-9.
(216)    Abdel-Latif A, Bolli R, Zuba-Surma EK, Tleyjeh IM, Hornung CA, and Dawn B. Granulocyte colony-stimulating factor therapy for cardiac repair after acute myocardial infarction: A systematic review and meta-analysis of randomized controlled trials. American Heart Journal. (2008) 156: 216-26.e9.
(217)    Mohammadi Nasr S, Rabiee N, Hajebi S, Ahmadi S, Fatahi Y, Hosseini M, Bagherzadeh M, Ghadiri AM, Rabiee M, Jajarmi V, and Webster TJ. Biodegradable Nanopolymers in Cardiac Tissue Engineering: From Concept Towards Nanomedicine. Int J Nanomedicine. (2020) 15: 4205-24.
(218)    Guo B and Ma PX. Conducting Polymers for Tissue Engineering. Biomacromolecules. (2018) 19: 1764-82.
(219)    Pina S, Ribeiro VP, Marques CF, Maia FR, Silva TH, Reis RL, and Oliveira JM. Scaffolding Strategies for Tissue Engineering and Regenerative Medicine Applications. Materials (Basel). (2019) 12:
(220)    Abdulghani S and Mitchell GR. Biomaterials for In Situ Tissue Regeneration: A Review. Biomolecules. (2019) 9:
(221)    Jayasinghe SN. Thoughts on Scaffolds. Adv Biosyst. (2017) 1: e1700067.
(222)    Chiu LL, Iyer RK, Reis LA, Nunes SS, and Radisic M. Cardiac tissue engineering: current state and perspectives. Front Biosci (Landmark Ed). (2012) 17: 1533-50.
(223)    Alrefai MT, Murali D, Paul A, Ridwan KM, Connell JM, and Shum-Tim D. Cardiac tissue engineering and regeneration using cell-based therapy. Stem Cells Cloning. (2015) 8: 81-101.
(224)    Kobayashi K and Suzuki K. Mesenchymal Stem/Stromal Cell-Based Therapy for Heart Failure - What Is the Best Source? Circ J. (2018) 82: 2222-32.
(225)    Barreto S, Hamel L, Schiatti T, Yang Y, and George V. Cardiac Progenitor Cells from Stem Cells: Learning from Genetics and Biomaterials. Cells. (2019) 8:
(226)    Jiang B, Yan L, Shamul JG, Hakun M, and He X. Stem cell therapy of myocardial infarction: a promising opportunity in bioengineering. Adv Ther (Weinh). (2020) 3:
(227)    Durrani S, Konoplyannikov M, Ashraf M, and Haider KH. Skeletal myoblasts for cardiac repair. Regen Med. (2010) 5: 919-32.
(228)    Breckwoldt K, Weinberger F, and Eschenhagen T. Heart regeneration. Biochim Biophys Acta. (2016) 1863: 1749-59.
(229)    Hashimoto H, Olson EN, and Bassel-Duby R. Therapeutic approaches for cardiac regeneration and repair. Nat Rev Cardiol. (2018) 15: 585-600.
(230)    FitzSimons M, Beauchemin M, Smith AM, Stroh EG, Kelpsch DJ, Lamb MC, Tootle TL, and Yin VP. Cardiac injury modulates critical components of prostaglandin E(2) signaling during zebrafish heart regeneration. Sci Rep. (2020) 10: 3095.
(231)    Guo X, Lu X, Yang J, and Kassab GS. Increased aortic stiffness elevates pulse and mean pressure and compromises endothelial function in Wistar rats. Am J Physiol Heart Circ Physiol. (2014) 307: H880-7.
(232)    Murakoshi M, Saiki K, Urayama K, and Sato TN. An anthelmintic drug, pyrvinium pamoate, thwarts fibrosis and ameliorates myocardial contractile dysfunction in a mouse model of myocardial infarction. PloS one. (2013) 8: e79374-e.
(233)    Fiordaliso F, Maggioni S, Balconi G, Schiarea S, Corbelli A, De Luigi A, Figliuzzi M, Antoniou X, Chiabrando C, Masson S, Cervo L, and Latini R. Effects of dipeptidyl peptidase-4 (DPP-4) inhibition on angiogenesis and hypoxic injury in type 2 diabetes. Life Sci. (2016) 154: 87-95.
(234)    Oduk Y, Zhu W, Kannappan R, Zhao M, Borovjagin AV, Oparil S, and Zhang JJ. VEGF nanoparticles repair the heart after myocardial infarction. Am J Physiol Heart Circ Physiol. (2018) 314: H278-h84.
(235)    Huang FY, Xia TL, Li JL, Li CM, Zhao ZG, Lei WH, Chen L, Liao YB, Xiao D, Peng Y, Wang YB, Liu XJ, and Chen M. The bifunctional SDF-1-AnxA5 fusion protein protects cardiac function after myocardial infarction. J Cell Mol Med. (2019) 23: 7673-84.
(236)    Rupert CE and Coulombe KL. The roles of neuregulin-1 in cardiac development, homeostasis, and disease. Biomark Insights. (2015) 10: 1-9.
(237)    Rupert CE and Coulombe KLK. IGF1 and NRG1 Enhance Proliferation, Metabolic Maturity, and the Force-Frequency Response in hESC-Derived Engineered Cardiac Tissues. Stem Cells Int. (2017) 2017: 7648409.
(238)    Spadaccio C, Nappi F, De Marco F, Sedati P, Taffon C, Nenna A, Crescenzi A, Chello M, Trombetta M, Gambardella I, and Rainer A. Implantation of a Poly-L-Lactide GCSF-Functionalized Scaffold in a Model of Chronic Myocardial Infarction. J Cardiovasc Transl Res. (2017) 10: 47-65.