{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T08:57:03Z","timestamp":1767862623740,"version":"3.49.0"},"reference-count":80,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"project INCardio, European Regional Development Fund","award":["Id24529"],"award-info":[{"award-number":["Id24529"]}]},{"name":"Interreg V-A Italy-Austria 2014\u20132020","award":["Id24529"],"award-info":[{"award-number":["Id24529"]}]},{"name":"Grant AIRC IG2020","award":["Id24529"],"award-info":[{"award-number":["Id24529"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cardiac development is characterized by the active proliferation of different cardiac cell types, in particular cardiomyocytes and endothelial cells, that eventually build the beating heart. In mammals, these cells lose their regenerative potential early after birth, representing a major obstacle to our current capacity to restore the myocardial structure and function after an injury. Increasing evidence indicates that the cardiac extracellular matrix (ECM) actively regulates and orchestrates the proliferation, differentiation, and migration of cardiac cells within the heart, and that any change in either the composition of the ECM or its mechanical properties ultimately affect the behavior of these cells throughout one\u2019s life. Thus, understanding the role of ECMs\u2019 proteins and related signaling pathways on cardiac cell proliferation is essential to develop effective strategies fostering the regeneration of a damaged heart. This review provides an overview of the components of the ECM and its mechanical properties, whose function in cardiac regeneration has been elucidated, with a major focus on the strengths and weaknesses of the experimental models so far exploited to demonstrate the actual pro-regenerative capacity of the components of the ECM and to translate this knowledge into new therapies.<\/jats:p>","DOI":"10.3390\/ijms232415783","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T01:56:06Z","timestamp":1670896566000},"page":"15783","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Extracellular Matrix-Based Approaches in Cardiac Regeneration: Challenges and Opportunities"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6698-424X","authenticated-orcid":false,"given":"Thi Van Anh","family":"Vu","sequence":"first","affiliation":[{"name":"Cardiovascular Biology Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149 Trieste, Italy"}]},{"given":"Daniela","family":"Lorizio","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino, 20138 Milano, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5519-248X","authenticated-orcid":false,"given":"Roman","family":"Vuerich","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149 Trieste, Italy"},{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy"}]},{"given":"Melania","family":"Lippi","sequence":"additional","affiliation":[{"name":"Centro Cardiologico Monzino, 20138 Milano, Italy"}]},{"given":"Diana S.","family":"Nascimento","sequence":"additional","affiliation":[{"name":"ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar da Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"INEB\u2014Instituto Nacional de Engenharia Biom\u00e9dica, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Serena","family":"Zacchigna","sequence":"additional","affiliation":[{"name":"Cardiovascular Biology Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149 Trieste, Italy"},{"name":"Centro Cardiologico Monzino, 20138 Milano, Italy"},{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.yjmcc.2015.09.017","article-title":"Harnessing the microRNA pathway for cardiac regeneration","volume":"89","author":"Giacca","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/j.tips.2022.06.001","article-title":"Biologics and cardiac disease: Challenges and opportunities","volume":"43","author":"Ciucci","year":"2022","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1126\/science.1200708","article-title":"Transient regenerative potential of the neonatal mouse heart","volume":"331","author":"Porrello","year":"2011","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Misra, A., Baker, C.D., Pritchett, E.M., Burgos Villar, K.N., Ashton, J.M., and Small, E.M. (2021). Characterizing Neonatal Heart Maturation, Regeneration, and Scar Resolution Using Spatial Transcriptomics. J. Cardiovasc. Dev. Dis., 9.","DOI":"10.3390\/jcdd9010001"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"621644","DOI":"10.3389\/fcell.2020.621644","article-title":"Bearing My Heart: The Role of Extracellular Matrix on Cardiac Development, Homeostasis, and Injury Response","volume":"8","author":"Silva","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"892763","DOI":"10.3389\/fmolb.2022.892763","article-title":"Comprehensive Mapping and Dynamics of Site-Specific Prolyl-Hydroxylation, Lysyl-Hydroxylation and Lysyl O-Glycosylation of Collagens Deposited in ECM During Zebrafish Heart Regeneration","volume":"9","author":"Sarohi","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11237","DOI":"10.1073\/pnas.1605431113","article-title":"Fast revascularization of the injured area is essential to support zebrafish heart regeneration","volume":"113","author":"Marass","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1006\/scdb.2000.0244","article-title":"Hyaluronan in morphogenesis","volume":"12","author":"Toole","year":"2001","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ydbio.2007.07.041","article-title":"Cartilage link protein 1 (Crtl1), an extracellular matrix component playing an important role in heart development","volume":"310","author":"Wirrig","year":"2007","journal-title":"Dev. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1161\/CIRCULATIONAHA.121.055468","article-title":"hapln1 Defines an Epicardial Cell Subpopulation Required for Cardiomyocyte Expansion During Heart Morphogenesis and Regeneration","volume":"146","author":"Sun","year":"2022","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature22978","article-title":"The extracellular matrix protein agrin promotes heart regeneration in mice","volume":"547","author":"Bassat","year":"2017","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1161\/CIRCULATIONAHA.119.045116","article-title":"Agrin Promotes Coordinated Therapeutic Processes Leading to Improved Cardiac Repair in Pigs","volume":"142","author":"Baehr","year":"2020","journal-title":"Circulation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1093\/cvr\/cvx001","article-title":"Ablation of periostin inhibits post-infarction myocardial regeneration in neonatal mice mediated by the phosphatidylinositol 3 kinase\/glycogen synthase kinase 3beta\/cyclin D1 signalling pathway","volume":"113","author":"Chen","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1038\/nm1619","article-title":"Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair","volume":"13","author":"Kuhn","year":"2007","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ladage, D., Yaniz-Galende, E., Rapti, K., Ishikawa, K., Tilemann, L., Shapiro, S., Takewa, Y., Muller-Ehmsen, J., Schwarz, M., and Garcia, M.J. (2013). Stimulating myocardial regeneration with periostin Peptide in large mammals improves function post-myocardial infarction but increases myocardial fibrosis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059656"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1161\/CIRCRESAHA.108.188649","article-title":"Genetic manipulation of periostin expression in the heart does not affect myocyte content, cell cycle activity, or cardiac repair","volume":"104","author":"Lorts","year":"2009","journal-title":"Circ. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1161\/HYPERTENSIONAHA.115.06265","article-title":"Selective Blockade of Periostin Exon 17 Preserves Cardiac Performance in Acute Myocardial Infarction","volume":"67","author":"Taniyama","year":"2016","journal-title":"Hypertension"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1161\/CIRCRESAHA.119.316303","article-title":"Modulation of Mammalian Cardiomyocyte Cytokinesis by the Extracellular Matrix","volume":"127","author":"Wu","year":"2020","journal-title":"Circ. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.ydbio.2013.08.012","article-title":"Fibronectin is deposited by injury-activated epicardial cells and is necessary for zebrafish heart regeneration","volume":"382","author":"Wang","year":"2013","journal-title":"Dev. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/gt.2012.17","article-title":"VEGF gene therapy: Therapeutic angiogenesis in the clinic and beyond","volume":"19","author":"Giacca","year":"2012","journal-title":"Gene Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1016\/j.jacc.2020.03.024","article-title":"Basic Biology of Extracellular Matrix in the Cardiovascular System, Part 1\/4: JACC Focus Seminar","volume":"75","author":"Fischer","year":"2020","journal-title":"J. Am.Coll. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1016\/j.jacc.2020.03.018","article-title":"Extracellular Matrix in Vascular Disease, Part 2\/4: JACC Focus Seminar","volume":"75","author":"Loeys","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mongiat, M., Andreuzzi, E., Tarticchio, G., and Paulitti, A. (2016). Extracellular Matrix, a Hard Player in Angiogenesis. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17111822"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1152\/physrev.00067.2017","article-title":"Wound Healing: A Cellular Perspective","volume":"99","author":"Rodrigues","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_25","first-page":"173ra125","article-title":"Safety and efficacy of an injectable extracellular matrix hydrogel for treating myocardial infarction","volume":"5","author":"Singelyn","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.jacc.2011.10.888","article-title":"Catheter-deliverable hydrogel derived from decellularized ventricular extracellular matrix increases endogenous cardiomyocytes and preserves cardiac function post-myocardial infarction","volume":"59","author":"Singelyn","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/j.jacc.2015.12.035","article-title":"Evidence for Mechanisms Underlying the Functional Benefits of a Myocardial Matrix Hydrogel for Post-MI Treatment","volume":"67","author":"Wassenaar","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/j.jacbts.2019.07.012","article-title":"First-in-Man Study of a Cardiac Extracellular Matrix Hydrogel in Early and Late Myocardial Infarction Patients","volume":"4","author":"Traverse","year":"2019","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nrm3904","article-title":"Remodelling the extracellular matrix in development and disease","volume":"15","author":"Bonnans","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1161\/CIRCRESAHA.119.315023","article-title":"Heparan Sulfate-Editing Extracellular Sulfatases Enhance VEGF Bioavailability for Ischemic Heart Repair","volume":"125","author":"Reboll","year":"2019","journal-title":"Circ. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19520","DOI":"10.1038\/s41598-021-98852-6","article-title":"Collagen fibers provide guidance cues for capillary regrowth during regenerative angiogenesis in zebrafish","volume":"11","author":"Senk","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.devcel.2019.10.019","article-title":"Coronary Revascularization During Heart Regeneration Is Regulated by Epicardial and Endocardial Cues and Forms a Scaffold for Cardiomyocyte Repopulation","volume":"51","author":"Helker","year":"2019","journal-title":"Dev. Cell"},{"key":"ref_33","first-page":"dev193219","article-title":"Ccn2a is an injury-induced matricellular factor that promotes cardiac regeneration in zebrafish","volume":"148","author":"Mukherjee","year":"2021","journal-title":"Development"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1161\/CIRCRESAHA.121.319929","article-title":"A Vegfc-Emilin2a-Cxcl8a Signaling Axis Required for Zebrafish Cardiac Regeneration","volume":"130","author":"Yang","year":"2022","journal-title":"Circ. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.jtcvs.2017.08.127","article-title":"Angiogenesis precedes cardiomyocyte migration in regenerating mammalian hearts","volume":"155","author":"Ingason","year":"2018","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"eaao5553","DOI":"10.1126\/sciadv.aao5553","article-title":"The local microenvironment limits the regenerative potential of the mouse neonatal heart","volume":"4","author":"Notari","year":"2018","journal-title":"Sci. Adv."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1161\/CIRCRESAHA.120.317685","article-title":"Multiscale Analysis of Extracellular Matrix Remodeling in the Failing Heart","volume":"128","author":"Perestrelo","year":"2021","journal-title":"Circ. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"20603","DOI":"10.1021\/acsami.9b02446","article-title":"Tunable and Reversible Substrate Stiffness Reveals a Dynamic Mechanosensitivity of Cardiomyocytes","volume":"11","author":"Corbin","year":"2019","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e07455","DOI":"10.7554\/eLife.07455","article-title":"Reduced matrix rigidity promotes neonatal cardiomyocyte dedifferentiation, proliferation and clonal expansion","volume":"4","author":"Rajchman","year":"2015","journal-title":"Elife"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1089\/ten.tea.2018.0274","article-title":"Quantifying the Vasculogenic Potential of Induced Pluripotent Stem Cell-Derived Endothelial Progenitors in Collagen Hydrogels","volume":"25","author":"Crosby","year":"2019","journal-title":"Tissue Eng. Part A"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.jacbts.2017.05.005","article-title":"Bioactive Extracellular Matrix Scaffold Promotes Adaptive Cardiac Remodeling and Repair","volume":"2","author":"Mewhort","year":"2017","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.actbio.2020.06.032","article-title":"Microenvironment stiffness requires decellularized cardiac extracellular matrix to promote heart regeneration in the neonatal mouse heart","volume":"113","author":"Wang","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4635","DOI":"10.1016\/j.actbio.2012.08.007","article-title":"Tuning three-dimensional collagen matrix stiffness independently of collagen concentration modulates endothelial cell behavior","volume":"9","author":"Mason","year":"2013","journal-title":"Acta Biomater."},{"key":"ref_44","first-page":"5029","article-title":"Lysyl oxidase inhibition via beta-aminoproprionitrile hampers human umbilical vein endothelial cell angiogenesis and migration in vitro","volume":"17","author":"Shi","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1074\/mcp.RA118.001193","article-title":"Proteomics Analysis of Extracellular Matrix Remodeling During Zebrafish Heart Regeneration","volume":"18","author":"Mosquera","year":"2019","journal-title":"Mol. Cell. Proteom."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1161\/CIRCULATIONAHA.111.056952","article-title":"Proteomics analysis of cardiac extracellular matrix remodeling in a porcine model of ischemia\/reperfusion injury","volume":"125","author":"Didangelos","year":"2012","journal-title":"Circulation"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nm1684","article-title":"Perfusion-decellularized matrix: Using nature\u2019s platform to engineer a bioartificial heart","volume":"14","author":"Ott","year":"2008","journal-title":"Nat. Med."},{"key":"ref_48","first-page":"e56924","article-title":"Comparable Decellularization of Fetal and Adult Cardiac Tissue Explants as 3D-like Platforms for In Vitro Studies","volume":"145","author":"Silva","year":"2019","journal-title":"J. Vis. Exp."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e1600844","DOI":"10.1126\/sciadv.1600844","article-title":"Decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration","volume":"2","author":"Chen","year":"2016","journal-title":"Sci. Adv."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.actbio.2013.08.037","article-title":"Young developmental age cardiac extracellular matrix promotes the expansion of neonatal cardiomyocytes in vitro","volume":"10","author":"Williams","year":"2014","journal-title":"Acta Biomater."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1039\/D1BM01539G","article-title":"In vivo evaluation of bioprinted cardiac patches composed of cardiac-specific extracellular matrix and progenitor cells in a model of pediatric heart failure","volume":"10","author":"Bejleri","year":"2022","journal-title":"Biomater. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e1800672","DOI":"10.1002\/adhm.201800672","article-title":"A Bioprinted Cardiac Patch Composed of Cardiac-Specific Extracellular Matrix and Progenitor Cells for Heart Repair","volume":"7","author":"Bejleri","year":"2018","journal-title":"Adv. Healthc. Mater."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e2102265","DOI":"10.1002\/adhm.202102265","article-title":"Injectable Extracellular Matrix Microparticles Promote Heart Regeneration in Mice with Post-ischemic Heart Injury","volume":"11","author":"Wang","year":"2022","journal-title":"Adv. Healthc. Mater."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1002\/adhm.201500035","article-title":"3rd. Partially Digested Adult Cardiac Extracellular Matrix Promotes Cardiomyocyte Proliferation In Vitro","volume":"4","author":"Williams","year":"2015","journal-title":"Adv. Healthc. Mater."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.biomaterials.2015.01.016","article-title":"PET imaging of a collagen matrix reveals its effective injection and targeted retention in a mouse model of myocardial infarction","volume":"49","author":"Ahmadi","year":"2015","journal-title":"Biomaterials"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"9048","DOI":"10.1016\/j.biomaterials.2013.08.017","article-title":"The effect of bioengineered acellular collagen patch on cardiac remodeling and ventricular function post myocardial infarction","volume":"34","author":"Serpooshan","year":"2013","journal-title":"Biomaterials"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"120554","DOI":"10.1016\/j.biomaterials.2020.120554","article-title":"Effect of cellular and ECM aging on human iPSC-derived cardiomyocyte performance, maturity and senescence","volume":"268","author":"Ozcebe","year":"2021","journal-title":"Biomaterials"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/j.athoracsur.2014.11.064","article-title":"Tissue reaction to porcine intestinal Submucosa (CorMatrix) implants in pediatric cardiac patients: A single-center experience","volume":"99","author":"Magid","year":"2015","journal-title":"Ann. Thorac. Surg."},{"key":"ref_59","first-page":"e98","article-title":"Deciphering Endothelial Heterogeneity in Health and Disease at Single Cell Resolution: Progress and Perspectives","volume":"118","author":"Becker","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1007\/s12015-022-10385-1","article-title":"Cardiac Organoids: A 3D Technology for Modeling Heart Development and Disease","volume":"18","author":"Zhu","year":"2022","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1161\/CIRCRESAHA.119.316155","article-title":"In Situ Expansion, Differentiation, and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid","volume":"127","author":"Kupfer","year":"2020","journal-title":"Circ. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4283","DOI":"10.1038\/s41467-020-18031-5","article-title":"In vitro generation of functional murine heart organoids via FGF4 and extracellular matrix","volume":"11","author":"Lee","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1016\/j.stem.2021.11.007","article-title":"Co-emergence of cardiac and gut tissues promotes cardiomyocyte maturation within human iPSC-derived organoids","volume":"28","author":"Silva","year":"2021","journal-title":"Cell Stem Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1002\/term.2680","article-title":"Aortic valve cell seeding into decellularized animal pericardium by perfusion-assisted bioreactor","volume":"12","author":"Amadeo","year":"2018","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Robertson, M.J., Dries-Devlin, J.L., Kren, S.M., Burchfield, J.S., and Taylor, D.A. (2014). Optimizing recellularization of whole decellularized heart extracellular matrix. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090406"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1007\/s10741-020-09953-9","article-title":"Extracellular matrix-based biomaterials for cardiac regeneration and repair","volume":"26","author":"Li","year":"2021","journal-title":"Heart Fail. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/nature08899","article-title":"Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation","volume":"464","author":"Jopling","year":"2010","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/s11936-013-0288-8","article-title":"Cardiac regeneration in model organisms","volume":"16","author":"Gamba","year":"2014","journal-title":"Curr. Treat. Options Cardiovasc. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature12111","article-title":"The zebrafish reference genome sequence and its relationship to the human genome","volume":"496","author":"Howe","year":"2013","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1038\/s41467-019-09716-7","article-title":"Humanising the mouse genome piece by piece","volume":"10","author":"Zhu","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.stemcr.2018.01.042","article-title":"Neonatal Apex Resection Triggers Cardiomyocyte Proliferation, Neovascularization and Functional Recovery Despite Local Fibrosis","volume":"10","author":"Rodrigues","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_72","first-page":"2307","article-title":"Qualitative research of alternatively splice variants of fibronectin in different development stage of mice heart","volume":"7","author":"Lu","year":"2015","journal-title":"J. Thorac. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ijcard.2021.06.015","article-title":"Functional heart recovery in an adult mammal, the spiny mouse","volume":"338","author":"Qi","year":"2021","journal-title":"Int. J. Cardiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1093\/icvts\/ivw020","article-title":"Small intestinal submucosa extracellular matrix (CorMatrix(R)) in cardiovascular surgery: A systematic review","volume":"22","author":"Poncelet","year":"2016","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1900344","DOI":"10.1002\/advs.201900344","article-title":"3D Printing of Personalized Thick and Perfusable Cardiac Patches and Hearts","volume":"6","author":"Noor","year":"2019","journal-title":"Adv. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jacbts.2016.11.008","article-title":"Designing Acellular Injectable Biomaterial Therapeutics for Treating Myocardial Infarction and Peripheral Artery Disease","volume":"2","author":"Hernandez","year":"2017","journal-title":"JACC Basic Transl. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature11739","article-title":"Functional screening identifies miRNAs inducing cardiac regeneration","volume":"492","author":"Eulalio","year":"2012","journal-title":"Nature"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/s41586-019-1191-6","article-title":"MicroRNA therapy stimulates uncontrolled cardiac repair after myocardial infarction in pigs","volume":"569","author":"Gabisonia","year":"2019","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.semcancer.2008.03.016","article-title":"Can cancer be reversed by engineering the tumor microenvironment?","volume":"18","author":"Ingber","year":"2008","journal-title":"Semin. Cancer Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1002\/bies.201100025","article-title":"The tissue organization field theory of cancer: A testable replacement for the somatic mutation theory","volume":"33","author":"Soto","year":"2011","journal-title":"BioEssays"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15783\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:40:10Z","timestamp":1760146810000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15783"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,13]]},"references-count":80,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232415783"],"URL":"https:\/\/doi.org\/10.3390\/ijms232415783","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,13]]}}}