Cardiac tissue engineering: state-of-the-art methods and outlook

The purpose of this review is to assess the state-of-the-art fabrication methods, advances in genome editing, and the use of machine learning to shape the prospective growth in cardiac tissue engineering. Those interdisciplinary emerging innovations would move forward basic research in this field and their clinical applications. The long-entrenched challenges in this field could be addressed by novel 3-dimensional (3D) scaffold substrates for cardiomyocyte (CM) growth and maturation. Stem cell-based therapy through genome editing techniques can repair gene mutation, control better maturation of CMs or even reveal its molecular clock. Finally, machine learning and precision control for improvements of the construct fabrication process and optimization in tissue-specific clonal selections with an outlook of cardiac tissue engineering are also presented.

[1]  Charles A. Gersbach,et al.  A CRISPR/Cas9-Based System for Reprogramming Cell Lineage Specification , 2014, Stem cell reports.

[2]  Nicholas J. Kaiser,et al.  Optimizing Blended Collagen-Fibrin Hydrogels for Cardiac Tissue Engineering with Human iPSC-derived Cardiomyocytes , 2018, ACS biomaterials science & engineering.

[3]  Donald M Bers,et al.  Integrated Ca2+ Management in Cardiac Myocytes , 2004, Annals of the New York Academy of Sciences.

[4]  Yang Xu,et al.  A Safety Checkpoint to Eliminate Cancer Risk of the Immune Evasive Cells Derived from Human Embryonic Stem Cells , 2017, Stem cells.

[5]  Jan Hošek,et al.  Designing of PLA scaffolds for bone tissue replacement fabricated by ordinary commercial 3D printer , 2017, Journal of Biological Engineering.

[6]  M. Morad,et al.  Generation and Characterization of CPVT1 Cardiomyocytes using Human Induced Pluripotent Stem Cells and CRISPR/Cas9 Gene Editing , 2018 .

[7]  B. Blagoev,et al.  Cellular Proteome Dynamics during Differentiation of Human Primary Myoblasts. , 2015, Journal of proteome research.

[8]  Milica Radisic,et al.  Electrical stimulation systems for cardiac tissue engineering , 2009, Nature Protocols.

[9]  Vladimir Mironov,et al.  Organ printing: tissue spheroids as building blocks. , 2009, Biomaterials.

[10]  John A. Tallarico,et al.  Integrating high-content screening and ligand-target prediction to identify mechanism of action. , 2008, Nature chemical biology.

[11]  T. Ma,et al.  Differential Effects of Heparin and Hyaluronic Acid on Neural Patterning of Human Induced Pluripotent Stem Cells. , 2018, ACS biomaterials science & engineering.

[12]  Jonathan M. Brunger,et al.  Tissue-engineered cartilage with inducible and tunable immunomodulatory properties. , 2014, Biomaterials.

[13]  Cecilia Laschi,et al.  Soft robotics: a bioinspired evolution in robotics. , 2013, Trends in biotechnology.

[14]  Sumona Sarkar,et al.  Machine learning based methodology to identify cell shape phenotypes associated with microenvironmental cues. , 2016, Biomaterials.

[15]  Soni Jyoti,et al.  Predictive Data Mining for Medical Diagnosis: An Overview of Heart Disease Prediction , 2011 .

[16]  Chunhui Xu,et al.  Stem-Cell-Derived Cardiomyocytes Grow Up: Start Young and Train Harder. , 2018, Cell stem cell.

[17]  L. Turng,et al.  Polycaprolactone Nanofibers Containing Vascular Endothelial Growth Factor-Encapsulated Gelatin Particles Enhance Mesenchymal Stem Cell Differentiation and Angiogenesis of Endothelial Cells. , 2018, Biomacromolecules.

[18]  Ronald A. Li,et al.  Machine Learning of Human Pluripotent Stem Cell-Derived Engineered Cardiac Tissue Contractility for Automated Drug Classification , 2017, Stem cell reports.

[19]  Sergey Plis,et al.  Deep Learning Applications for Predicting Pharmacological Properties of Drugs and Drug Repurposing Using Transcriptomic Data. , 2016, Molecular pharmaceutics.

[20]  G. von Heijne,et al.  Tissue-based map of the human proteome , 2015, Science.

[21]  Claire Berry Artificial intelligence and the dental practitioner , 2019, BDJ In Practice.

[22]  V. Balashov,et al.  High resolution 3D microscopy study of cardiomyocytes on polymer scaffold nanofibers reveals formation of unusual sheathed structure. , 2017, Acta biomaterialia.

[23]  Richard T. Lee,et al.  Adult Cardiac Stem Cell Concept and the Process of Science , 2018, Circulation.

[24]  Ashley J. Waardenberg,et al.  Genetic networks governing heart development. , 2014, Cold Spring Harbor perspectives in medicine.

[25]  Andrej J. Savol,et al.  Macrophages Facilitate Electrical Conduction in the Heart , 2017, Cell.

[26]  Giles M. Foody,et al.  Multiclass and Binary SVM Classification: Implications for Training and Classification Users , 2008, IEEE Geoscience and Remote Sensing Letters.

[27]  C. Bouten,et al.  Cardiac Progenitor Cells and the Interplay with Their Microenvironment , 2017, Stem cells international.

[28]  V. Martinelli,et al.  Biomimetic Polymers for Cardiac Tissue Engineering , 2016, Biomacromolecules.

[29]  Lil Pabon,et al.  Engineering Adolescence: Maturation of Human Pluripotent Stem Cell–Derived Cardiomyocytes , 2014, Circulation research.

[30]  J. A. V. BUTLER,et al.  Theory of the Stability of Lyophobic Colloids , 1948, Nature.

[31]  B. Knollmann,et al.  Thyroid and Glucocorticoid Hormones Promote Functional T-Tubule Development in Human-Induced Pluripotent Stem Cell–Derived Cardiomyocytes , 2017, Circulation research.

[32]  K. Shung,et al.  Electrical and Mechanical Strategies to Enable Cardiac Repair and Regeneration , 2015, IEEE Reviews in Biomedical Engineering.

[33]  P. Ma,et al.  Interwoven Aligned Conductive Nanofiber Yarn/Hydrogel Composite Scaffolds for Engineered 3D Cardiac Anisotropy. , 2017, ACS nano.

[34]  Ciro Indolfi,et al.  Adult c-kitpos Cardiac Stem Cells Are Necessary and Sufficient for Functional Cardiac Regeneration and Repair , 2013, Cell.

[35]  Isuru D. Jayasinghe,et al.  Comparison of the organization of t‐tubules, sarcoplasmic reticulum and ryanodine receptors in rat and human ventricular myocardium , 2012 .

[36]  G. Schulze-Tanzil,et al.  PLLA scaffolds produced by thermally induced phase separation (TIPS) allow human chondrocyte growth and extracellular matrix formation dependent on pore size. , 2017, Materials science & engineering. C, Materials for biological applications.

[37]  X. Cui,et al.  Heart Repair Using Nanogel-Encapsulated Human Cardiac Stem Cells in Mice and Pigs with Myocardial Infarction , 2017, ACS nano.

[38]  Zhang Boyang,et al.  A highly elastic and moldable polyester biomaterial for cardiac tissue engineering applications , 2016 .

[39]  Joshua M. Stuart,et al.  Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation. , 2018, Cell.

[40]  Michael Z. Lin,et al.  A Single-Chain Photoswitchable CRISPR-Cas9 Architecture for Light-Inducible Gene Editing and Transcription , 2017, ACS chemical biology.

[41]  L. Ferreira,et al.  Restoring heart function and electrical integrity: closing the circuit , 2017, npj Regenerative Medicine.

[42]  Yan Xia,et al.  Organic/inorganic composite membranes based on poly(L-lactic-co-glycolic acid) and mesoporous silica for effective bone tissue engineering. , 2014, ACS applied materials & interfaces.

[43]  Fabien Guillemot,et al.  In vivo bioprinting for computer- and robotic-assisted medical intervention: preliminary study in mice , 2010, Biofabrication.

[44]  Sebastian Thrun,et al.  Dermatologist-level classification of skin cancer with deep neural networks , 2017, Nature.

[45]  L. Zentilin,et al.  A mouse model for adult cardiac-specific gene deletion with CRISPR/Cas9 , 2015, Proceedings of the National Academy of Sciences.

[46]  G. Gaudette,et al.  Development of a Contractile Cardiac Fiber From Pluripotent Stem Cell Derived Cardiomyocytes , 2018, Front. Cardiovasc. Med..

[47]  G. Vunjak‐Novakovic,et al.  Electrically Conductive Chitosan/Carbon Scaffolds for Cardiac Tissue Engineering , 2014, Biomacromolecules.

[48]  Manoel Luis Costa,et al.  2D and 3D-Organized Cardiac Cells Shows Differences in Cellular Morphology, Adhesion Junctions, Presence of Myofibrils and Protein Expression , 2012, PloS one.

[49]  Sheng Lin-Gibson,et al.  Systematic investigation of porogen size and content on scaffold morphometric parameters and properties. , 2007, Biomacromolecules.

[50]  David L Kaplan,et al.  Electrical and mechanical stimulation of cardiac cells and tissue constructs. , 2016, Advanced drug delivery reviews.

[51]  M. Brenner,et al.  An Inducible Caspase-9 Suicide Gene to Improve the Safety of Therapy Using Human Induced Pluripotent Stem Cells. , 2015, Molecular therapy : the journal of the American Society of Gene Therapy.

[52]  Jonathan M. Brunger,et al.  CRISPR/Cas9 Editing of Murine Induced Pluripotent Stem Cells for Engineering Inflammation‐Resistant Tissues , 2017, Arthritis & rheumatology.

[53]  D. Freimark,et al.  CRISPR correction of the PRKAG2 gene mutation in the patient's induced pluripotent stem cell-derived cardiomyocytes eliminates electrophysiological and structural abnormalities. , 2017, Heart rhythm.

[54]  M. Goumans,et al.  Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair , 2017, Circulation.

[55]  E. R. Davies Computer and Machine Vision: Theory, Algorithms, Practicalities , 2012 .

[56]  M. Ruel,et al.  Nanoengineered Electroconductive Collagen-Based Cardiac Patch for Infarcted Myocardium Repair. , 2018, ACS applied materials & interfaces.

[57]  Aldo A. Faisal,et al.  The Artificial Intelligence Clinician learns optimal treatment strategies for sepsis in intensive care , 2018, Nature Medicine.

[58]  M. Lisanti,et al.  Differential targeting of beta -adrenergic receptor subtypes and adenylyl cyclase to cardiomyocyte caveolae. A mechanism to functionally regulate the cAMP signaling pathway. , 2000, The Journal of biological chemistry.

[59]  L. Moran,et al.  Gray level Co‐occurrence Matrices (GLCM) to assess microstructural and textural changes in pre‐implantation embryos , 2016, Molecular reproduction and development.

[60]  Yufeng Zheng,et al.  Constructing Multilayer Silk Protein/Nanosilver Biofunctionalized Hierarchically Structured 3D Printed Ti6Al4 V Scaffold for Repair of Infective Bone Defects. , 2018, ACS biomaterials science & engineering.

[61]  F. Nicotra,et al.  Phage-displayed peptides targeting specific tissues and organs , 2018, Journal of drug targeting.

[62]  Elazer R Edelman,et al.  Vascular Tissue Engineering: Progress, Challenges, and Clinical Promise. , 2018, Cell stem cell.

[63]  Jeffry D. Sander,et al.  CRISPR-Cas systems for editing, regulating and targeting genomes , 2014, Nature Biotechnology.

[64]  Kevin Kit Parker,et al.  Structural Phenotyping of Stem Cell-Derived Cardiomyocytes , 2015, Stem cell reports.

[65]  Zhicheng Guan,et al.  Effect of electric field distribution uniformity on electrospinning , 2008 .

[66]  Le Cong,et al.  Multiplex Genome Engineering Using CRISPR/Cas Systems , 2013, Science.

[67]  Chee Meng Benjamin Ho,et al.  Femtosecond-Laser-Based 3D Printing for Tissue Engineering and Cell Biology Applications. , 2017, ACS biomaterials science & engineering.

[68]  T. Hoshino,et al.  Chemical switching of jellyfish-shaped micro robot consisting only of cardiomyocyte gel , 2011, 2011 16th International Solid-State Sensors, Actuators and Microsystems Conference.

[69]  Gianluca Ciardelli,et al.  Biomimetic materials and scaffolds for myocardial tissue regeneration. , 2013, Macromolecular bioscience.

[70]  Jie Song,et al.  3D‐Printed Biomaterials for Guided Tissue Regeneration , 2018 .

[71]  Zakariya Yahya Algamal,et al.  Tuning parameter estimation in SCAD-support vector machine using firefly algorithm with application in gene selection and cancer classification , 2018, Comput. Biol. Medicine.

[72]  R. Muschel,et al.  Correction to ‘Estimating oxygen distribution from vasculature in three-dimensional tumour tissue’ , 2016, Journal of The Royal Society Interface.

[73]  Jin-Oh You,et al.  Nanoengineering the heart: conductive scaffolds enhance connexin 43 expression. , 2011, Nano letters.

[74]  M. Edirisinghe,et al.  A novel method of selecting solvents for polymer electrospinning , 2010 .

[75]  Rui L Reis,et al.  Phage Display Technology in Biomaterials Engineering: Progress and Opportunities for Applications in Regenerative Medicine. , 2016, ACS chemical biology.

[76]  I. Karakikes,et al.  Human induced pluripotent stem cell-derived cardiomyocytes: insights into molecular, cellular, and functional phenotypes. , 2015, Circulation research.

[77]  Assaf Shapira,et al.  Gold nanoparticle-decellularized matrix hybrids for cardiac tissue engineering. , 2014, Nano letters.

[78]  Kathy O. Lui,et al.  Genetic Lineage Tracing of Nonmyocyte Population by Dual Recombinases , 2018, Circulation.

[79]  Stefania Raimondo,et al.  Role of Extracellular Vesicles in Hematological Malignancies , 2015, BioMed research international.

[80]  E. Verwey,et al.  Theory of the stability of lyophobic colloids. , 1955, The Journal of physical and colloid chemistry.

[81]  W. Cook,et al.  Increased Cardiomyocyte Alignment and Intracellular Calcium Transients Using Micropatterned and Drug-Releasing Poly(Glycerol Sebacate) Elastomers. , 2018, ACS biomaterials science & engineering.

[82]  Milica Radisic,et al.  Materials science and tissue engineering: repairing the heart. , 2013, Mayo Clinic proceedings.

[83]  Anamika Singh,et al.  Oxygen-Releasing Antioxidant Cryogel Scaffolds with Sustained Oxygen Delivery for Tissue Engineering Applications. , 2018, ACS applied materials & interfaces.

[84]  M. Khine,et al.  A Micropatterned Human Pluripotent Stem Cell‐Based Ventricular Cardiac Anisotropic Sheet for Visualizing Drug‐Induced Arrhythmogenicity , 2017, Advanced materials.

[85]  Bozhi Tian,et al.  Nanowires and Electrical Stimulation Synergistically Improve Functions of hiPSC Cardiac Spheroids. , 2016, Nano letters.

[86]  Michael D. Schneider,et al.  Cardiac progenitor cells from adult myocardium: Homing, differentiation, and fusion after infarction , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[87]  Younan Xia,et al.  Electrospun Nanofibers: New Concepts, Materials, and Applications. , 2017, Accounts of chemical research.

[88]  P. Kirshbom,et al.  Force Frequency Relationship of the Human Ventricle Increases During Early Postnatal Development , 2009, Pediatric Research.

[89]  Eliot L. Siegel,et al.  Machine Meets Biology: a Primer on Artificial Intelligence in Cardiology and Cardiac Imaging , 2018, Current Cardiology Reports.

[90]  D. Cho,et al.  Evaluation of solid free-form fabrication-based scaffolds seeded with osteoblasts and human umbilical vein endothelial cells for use in vivo osteogenesis. , 2010, Tissue engineering. Part A.

[91]  Marco Costantini,et al.  A multi-cellular 3D bioprinting approach for vascularized heart tissue engineering based on HUVECs and iPSC-derived cardiomyocytes , 2018, Scientific Reports.

[92]  A. Bender,et al.  Analysis of Pharmacology Data and the Prediction of Adverse Drug Reactions and Off‐Target Effects from Chemical Structure , 2007, ChemMedChem.

[93]  H. Clevers,et al.  Profiling proliferative cells and their progeny in damaged murine hearts , 2018, Proceedings of the National Academy of Sciences.

[94]  Shoji Takeuchi,et al.  Biohybrid robot powered by an antagonistic pair of skeletal muscle tissues , 2018, Science Robotics.

[95]  S. Levenberg,et al.  Oscillatory Strain Promotes Vessel Stabilization and Alignment through Fibroblast YAP‐Mediated Mechanosensitivity , 2018, Advanced science.

[96]  Rickey E. Carter,et al.  Screening for cardiac contractile dysfunction using an artificial intelligence–enabled electrocardiogram , 2019, Nature Medicine.

[97]  Vladimir Mironov,et al.  Review: bioprinting: a beginning. , 2006, Tissue engineering.

[98]  Ahmad Mozaffari,et al.  Application of self-learning evolutionary algorithm for optimal design of a porous polymethylmethacrylate scaffold fabricated by laser drilling process , 2013 .

[99]  D. Kaplan,et al.  Silk-Graphene Hybrid Hydrogels with Multiple Cues to Induce Nerve Cell Behavior. , 2018, ACS biomaterials science & engineering.

[100]  Xiongbiao Chen,et al.  3D biofabrication of vascular networks for tissue regeneration: A report on recent advances , 2018, Journal of pharmaceutical analysis.

[101]  Tilo Kircher,et al.  Support Vector Machine Analysis of Functional Magnetic Resonance Imaging of Interoception Does Not Reliably Predict Individual Outcomes of Cognitive Behavioral Therapy in Panic Disorder with Agoraphobia , 2017, Front. Psychiatry.

[102]  Hilde van der Togt,et al.  Publisher's Note , 2003, J. Netw. Comput. Appl..

[103]  J. Molkentin,et al.  An emerging consensus on cardiac regeneration , 2014, Nature Medicine.

[104]  Fan Wang,et al.  Paracrine Action of Mesenchymal Stem Cells Revealed by Single Cell Gene Profiling in Infarcted Murine Hearts , 2015, PloS one.

[105]  A. Dukhin Chapter 2 – Fundamentals of Interface and Colloid Science , 2017 .

[106]  Liang Zhong,et al.  Multi-dimensional proprio-proximus machine learning for assessment of myocardial infarction , 2018, Comput. Medical Imaging Graph..

[107]  J. Holmes,et al.  Role of boundary conditions in determining cell alignment in response to stretch , 2018, Proceedings of the National Academy of Sciences.

[108]  P. Ma,et al.  Electrospun conductive nanofibrous scaffolds for engineering cardiac tissue and 3D bioactuators. , 2017, Acta biomaterialia.

[109]  A. Hicks,et al.  The Impact of CRISPR/Cas9 Technology on Cardiac Research: From Disease Modelling to Therapeutic Approaches , 2017, Stem cells international.

[110]  M. Edirisinghe,et al.  Mapping the Influence of Solubility and Dielectric Constant on Electrospinning Polycaprolactone Solutions , 2012 .

[111]  T. Matsui,et al.  The Cardiomyocyte as a Source of Cytokines in Cardiac Injury. , 2011, Journal of cell science & therapy.

[112]  A. Vadivel Murugan,et al.  Noninvasive Tracking and Regenerative Capabilities of Transplanted Human Umbilical Cord-Derived Mesenchymal Stem Cells Labeled with I-III-IV Semiconducting Nanocrystals in Liver-Injured Living Mice. , 2019, ACS applied materials & interfaces.

[113]  A. Boccaccini,et al.  Effect of substrate mechanics on cardiomyocyte maturation and growth. , 2015, Tissue engineering. Part B, Reviews.

[114]  Milica Radisic,et al.  Biomaterials in myocardial tissue engineering , 2016, Journal of tissue engineering and regenerative medicine.

[115]  L. Braun [Age as a risk factor]. , 1986, Langenbecks Archiv fur Chirurgie.

[116]  V. Martinelli,et al.  3D Carbon-Nanotube-Based Composites for Cardiac Tissue Engineering. , 2018, ACS applied bio materials.

[117]  Ronald M. McLaughlin,et al.  Myocardial scaffold-based cardiac tissue engineering: application of coordinated mechanical and electrical stimulations. , 2013, Langmuir : the ACS journal of surfaces and colloids.

[118]  Alireza Fathi,et al.  Optimal design of a 3D-printed scaffold using intelligent evolutionary algorithms , 2016, Appl. Soft Comput..

[119]  Yang Wang,et al.  Applications of Support Vector Machine (SVM) Learning in Cancer Genomics. , 2018, Cancer genomics & proteomics.

[120]  M. Sorayya,et al.  Preliminary Study on Application of Machine Learning Method in Predicting Survival Versus Non-Survival after Myocardial Infarction in Malaysian Population , 2018, International Journal of Cardiology.

[121]  Markus Krane,et al.  Genome Editing Redefines Precision Medicine in the Cardiovascular Field , 2018, Stem cells international.

[122]  Hanmin Wang,et al.  Cardiac induction of embryonic stem cells by a small molecule inhibitor of Wnt/β-catenin signaling. , 2011, ACS chemical biology.

[123]  Metin Sitti,et al.  Bio-hybrid cell-based actuators for microsystems. , 2014, Small.

[124]  Ali Khademhosseini,et al.  Electrospun scaffolds for tissue engineering of vascular grafts. , 2014, Acta biomaterialia.

[125]  V. K. Raghunathan,et al.  Impact of Nanotopography, Heparin Hydrogel Microstructures, and Encapsulated Fibroblasts on Phenotype of Primary Hepatocytes , 2014, ACS applied materials & interfaces.

[126]  K. Franchini,et al.  A role for focal adhesion kinase in cardiac mitochondrial biogenesis induced by mechanical stress. , 2011, American journal of physiology. Heart and circulatory physiology.

[127]  Daisuke Komura,et al.  Machine Learning Methods for Histopathological Image Analysis , 2017, Computational and structural biotechnology journal.

[128]  M. Fornage,et al.  Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association , 2017, Circulation.

[129]  Ye Zhu,et al.  Phage Nanofibers Induce Vascularized Osteogenesis in 3D Printed Bone Scaffolds , 2014, Advanced materials.

[130]  M. Mrksich,et al.  Using Self-Assembled Monolayers To Understand α8β1-Mediated Cell Adhesion to RGD and FEI Motifs in Nephronectin , 2011, ACS chemical biology.

[131]  Huafeng Liu,et al.  Deep Learning Assessment of Myocardial Infarction From MR Image Sequences , 2019, IEEE Access.

[132]  R. Barker,et al.  The Challenges of First-in-Human Stem Cell Clinical Trials: What Does This Mean for Ethics and Institutional Review Boards? , 2018, Stem cell reports.

[133]  Steven C George,et al.  Three-Dimensional Adult Cardiac Extracellular Matrix Promotes Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. , 2016, Tissue engineering. Part A.

[134]  Udayabhanu M. Jammalamadaka,et al.  Recent Advances in Biomaterials for 3D Printing and Tissue Engineering , 2018, Journal of functional biomaterials.

[135]  M. Edirisinghe,et al.  Solubility–spinnability map and model for the preparation of fibres of polyethylene (terephthalate) using gyration and pressure , 2015 .

[136]  C. Gersbach,et al.  A light-inducible CRISPR/Cas9 system for control of endogenous gene activation , 2015, Nature chemical biology.

[137]  Sean Ekins,et al.  Exploiting machine learning for end-to-end drug discovery and development , 2019, Nature Materials.

[138]  Vladimir Mironov,et al.  Organ printing: from bioprinter to organ biofabrication line. , 2011, Current opinion in biotechnology.

[139]  S. Spirk,et al.  Interaction of Tissue Engineering Substrates with Serum Proteins and Its Influence on Human Primary Endothelial Cells. , 2017, Biomacromolecules.

[140]  Dimitrios Kontziampasis,et al.  Fibers for hearts: A critical review on electrospinning for cardiac tissue engineering. , 2017, Acta biomaterialia.

[141]  Christoph Sommer,et al.  Machine learning in cell biology – teaching computers to recognize phenotypes , 2013, Journal of Cell Science.

[142]  Jae-Hwan Jhong,et al.  Erratum to: Meta-analytic support vector machine for integrating multiple omics data , 2017, BioData Mining.

[143]  Coryandar Gilvary,et al.  A Machine Learning Approach Predicts Tissue-Specific Drug Adverse Events , 2018, bioRxiv.

[144]  René Vidal,et al.  Automated Grouping of Action Potentials of Human Embryonic Stem Cell-Derived Cardiomyocytes , 2014, IEEE Transactions on Biomedical Engineering.

[145]  Lawrence Buja,et al.  Oncosis: an important non-apoptotic mode of cell death. , 2012, Experimental and molecular pathology.

[146]  Chris Denning,et al.  CRISPR/Cas9 editing in human pluripotent stem cell-cardiomyocytes highlights arrhythmias, hypocontractility, and energy depletion as potential therapeutic targets for hypertrophic cardiomyopathy , 2018, European heart journal.

[147]  M. Ohkuma,et al.  Interaction of Bacterial Membrane Vesicles with Specific Species and Their Potential for Delivery to Target Cells , 2017, Front. Microbiol..

[148]  F. Rahimi,et al.  Paracrine Mechanisms Involved in Mesenchymal Stem Cell Differentiation into Cardiomyocytes. , 2019, Current stem cell research & therapy.

[149]  R. Pei,et al.  Bone Marrow-Derived Mesenchymal Stem Cells Encapsulated in Functionalized Gellan Gum/Collagen Hydrogel for Effective Vascularization. , 2018, ACS Applied Bio Materials.

[150]  H. Jeon,et al.  Genetically Engineered Phage Induced Selective H9c2 Cardiomyocytes Patterning in PDMS Microgrooves , 2017, Materials.

[151]  Benjamin L. Oakes,et al.  CRISPR-CasX is an RNA-dominated enzyme active for human genome editing , 2019, Nature.

[152]  Masoumeh Haghpanahi,et al.  Cardiologist-level arrhythmia detection and classification in ambulatory electrocardiograms using a deep neural network , 2019, Nature Medicine.

[153]  C. Murry,et al.  Hallmarks of cardiac regeneration , 2018, Nature Reviews Cardiology.

[154]  J. Poulos The limited application of stem cells in medicine: a review , 2018, Stem Cell Research & Therapy.

[155]  Anamika Singh,et al.  Engineering Bioinspired Antioxidant Materials Promoting Cardiomyocyte Functionality and Maturation for Tissue Engineering Application. , 2018, ACS applied materials & interfaces.

[156]  H. Calkins,et al.  Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs , 2012, Nature.

[157]  C. V. van Blitterswijk,et al.  Tailorable Surface Morphology of 3D Scaffolds by Combining Additive Manufacturing with Thermally Induced Phase Separation. , 2017, Macromolecular rapid communications.

[158]  Mikaël M. Martino,et al.  Extracellular Matrix-Inspired Growth Factor Delivery Systems for Skin Wound Healing. , 2015, Advances in wound care.

[159]  Wei Sun,et al.  3D Printing of Shear-Thinning Hyaluronic Acid Hydrogels with Secondary Cross-Linking. , 2016, ACS biomaterials science & engineering.

[160]  Christine L. Mummery,et al.  Contractile Defect Caused by Mutation in MYBPC3 Revealed under Conditions Optimized for Human PSC-Cardiomyocyte Function , 2015, Cell reports.

[161]  C. Indolfi,et al.  Adult cardiac stem cells are multipotent and robustly myogenic: c-kit expression is necessary but not sufficient for their identification , 2017, Cell Death and Differentiation.

[162]  Thomas J. Hinton,et al.  3D Printing PDMS Elastomer in a Hydrophilic Support Bath via Freeform Reversible Embedding , 2016, ACS biomaterials science & engineering.

[163]  Z. Xia,et al.  Osteogenic Potential of Human Umbilical Cord Mesenchymal Stem Cells on Coralline Hydroxyapatite/Calcium Carbonate Microparticles , 2018, Stem cells international.

[164]  Charles E. Murry,et al.  Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate Non-Human Primate Hearts , 2014, Nature.

[165]  F. Akar,et al.  Gene therapy to restore electrophysiological function in heart failure , 2015, Expert opinion on biological therapy.

[166]  Subhashini Venugopalan,et al.  Development and Validation of a Deep Learning Algorithm for Detection of Diabetic Retinopathy in Retinal Fundus Photographs. , 2016, JAMA.

[167]  L. Brunham,et al.  CRISPR/Cas9-mediated genome editing in human stem cell-derived cardiomyocytes: Applications for cardiovascular disease modelling and cardiotoxicity screening. , 2018, Drug discovery today. Technologies.

[168]  Pierre Baldi,et al.  A machine learning information retrieval approach to protein fold recognition. , 2006, Bioinformatics.

[169]  Keivan Maghooli,et al.  Improving Classification of Cancer and Mining Biomarkers from Gene Expression Profiles Using Hybrid Optimization Algorithms and Fuzzy Support Vector Machine , 2018, Journal of medical signals and sensors.

[170]  Joseph C. Wu,et al.  Strategies for Improving the Maturity of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes. , 2018, Circulation research.

[171]  Kevin Kit Parker,et al.  Nanofiber assembly by rotary jet-spinning. , 2010, Nano letters.

[172]  Hojung Nam,et al.  SELF-BLM: Prediction of drug-target interactions via self-training SVM , 2017, PloS one.

[173]  A. Bagchi,et al.  Innate immune response in the pathogenesis of heart failure in survivors of myocardial infarction. , 2019, American journal of physiology. Heart and circulatory physiology.

[174]  D. Srivastava,et al.  Regulation of Cell Cycle to Stimulate Adult Cardiomyocyte Proliferation and Cardiac Regeneration , 2017, Cell.

[175]  Peter M. Krawitz,et al.  Identifying facial phenotypes of genetic disorders using deep learning , 2019, Nature Medicine.

[176]  Jason A Burdick,et al.  Nanofibrous Hydrogels with Spatially Patterned Biochemical Signals to Control Cell Behavior , 2015, Advanced materials.

[177]  Won Ho Park,et al.  Electrospinning of silk fibroin nanofibers and its effect on the adhesion and spreading of normal human keratinocytes and fibroblasts in vitro. , 2004, Biomaterials.

[178]  Christopher T. Johnson,et al.  Evaluation of Hydrogels Presenting Extracellular Matrix-Derived Adhesion Peptides and Encapsulating Cardiac Progenitor Cells for Cardiac Repair. , 2018, ACS biomaterials science & engineering.

[179]  Brian A. Aguado,et al.  Injectable Carbon Nanotube-Functionalized Reverse Thermal Gel Promotes Cardiomyocytes Survival and Maturation. , 2017, ACS applied materials & interfaces.

[180]  Ali Khademhosseini,et al.  Directed 3D cell alignment and elongation in microengineered hydrogels. , 2010, Biomaterials.

[181]  I. Gomez,et al.  Cardiomyocytes and Macrophages Discourse on the Method to Govern Cardiac Repair , 2018, Front. Cardiovasc. Med..

[182]  VLADIMIR MIRONOV,et al.  Bioprinting : A Beginning , 2022 .

[183]  C. Alemán,et al.  Electrospun Conducting and Biocompatible Uniaxial and Core–Shell Fibers Having Poly(lactic acid), Poly(ethylene glycol), and Polyaniline for Cardiac Tissue Engineering , 2019, ACS omega.

[184]  Ali Khademhosseini,et al.  Microfluidic techniques for development of 3D vascularized tissue. , 2014, Biomaterials.

[185]  David E James,et al.  Functional screening in human cardiac organoids reveals a metabolic mechanism for cardiomyocyte cell cycle arrest , 2017, Proceedings of the National Academy of Sciences.

[186]  Andrew Janowczyk,et al.  Deep learning for digital pathology image analysis: A comprehensive tutorial with selected use cases , 2016, Journal of pathology informatics.

[187]  Eugene K. Lee,et al.  Machine learning plus optical flow: a simple and sensitive method to detect cardioactive drugs , 2015, Scientific Reports.

[188]  P. Clemons,et al.  Target identification and mechanism of action in chemical biology and drug discovery. , 2013, Nature chemical biology.

[189]  Claire Yu,et al.  Fabrication of Extracellular Matrix-derived Foams and Microcarriers as Tissue-specific Cell Culture and Delivery Platforms , 2017, Journal of visualized experiments : JoVE.

[190]  Yue Wu,et al.  Generating retinal flow maps from structural optical coherence tomography with artificial intelligence , 2018, Scientific Reports.

[191]  S. Ramakrishna,et al.  Technological advances in electrospinning of nanofibers , 2011, Science and technology of advanced materials.

[192]  Magdi H. Yacoub,et al.  Hydrogel scaffolds for tissue engineering: Progress and challenges , 2013, Global cardiology science & practice.

[193]  Ulrike von Luxburg,et al.  A tutorial on spectral clustering , 2007, Stat. Comput..

[194]  Salim E. Olia,et al.  Heart valve scaffold fabrication: Bioinspired control of macro-scale morphology, mechanics and micro-structure. , 2018, Biomaterials.

[195]  Andrei S. Dukhin,et al.  Fundamentals of Interface and Colloid Science , 2010 .

[196]  P. Gee,et al.  Cellular Reprogramming, Genome Editing, and Alternative CRISPR Cas9 Technologies for Precise Gene Therapy of Duchenne Muscular Dystrophy , 2017, Stem cells international.

[197]  Thomas Nixon,et al.  Feasibility of simple machine learning approaches to support detection of non-glaucomatous visual fields in future automated glaucoma clinics , 2019, Eye.

[198]  Antonios G Mikos,et al.  Biomimetic materials for tissue engineering. , 2003, Biomaterials.

[199]  Q. Pei,et al.  Advances in dielectric elastomers for actuators and artificial muscles. , 2010, Macromolecular rapid communications.

[200]  Todd R. Heallen,et al.  Heart repair via cardiomyocyte-secreted vesicles , 2018, Nature Biomedical Engineering.

[201]  N. Khaper,et al.  Inflammatory cytokines and postmyocardial infarction remodeling. , 2004, Circulation research.

[202]  R. Bragós,et al.  Simultaneous Electrical and Mechanical Stimulation to Enhance Cells' Cardiomyogenic Potential. , 2019, Journal of visualized experiments : JoVE.

[203]  Ka-Chun Wong,et al.  Off-target predictions in CRISPR-Cas9 gene editing using deep learning , 2018, Bioinform..

[204]  T. Park,et al.  Porous biodegradable polymeric scaffolds prepared by thermally induced phase separation. , 1999, Journal of biomedical materials research.

[205]  J. Lewis,et al.  3D Bioprinting of Vascularized, Heterogeneous Cell‐Laden Tissue Constructs , 2014, Advanced materials.

[206]  N. Rosenthal,et al.  Revisiting Cardiac Cellular Composition. , 2016, Circulation research.

[207]  Gordana Vunjak-Novakovic,et al.  Advanced maturation of human cardiac tissue grown from pluripotent stem cells , 2018, Nature.

[208]  Yuanjin Zhao,et al.  Cardiomyocyte-Driven Structural Color Actuation in Anisotropic Inverse Opals. , 2018, ACS nano.

[209]  Xuetao Sun,et al.  Biowire platform for maturation of human pluripotent stem cell-derived cardiomyocytes. , 2016, Methods.

[210]  Xin Jia,et al.  AuNP–Collagen Matrix with Localized Stiffness for Cardiac‐Tissue Engineering: Enhancing the Assembly of Intercalated Discs by β1‐Integrin‐Mediated Signaling , 2016, Advanced materials.

[211]  R. Bashir,et al.  Enabling microscale and nanoscale approaches for bioengineered cardiac tissue. , 2013, ACS nano.

[212]  I. Martin,et al.  Challenges for mesenchymal stromal cell therapies , 2019, Science Translational Medicine.

[213]  Kwideok Park,et al.  Novel Platform of Cardiomyocyte Culture and Coculture via Fibroblast-Derived Matrix-Coupled Aligned Electrospun Nanofiber. , 2017, ACS applied materials & interfaces.

[214]  John B. O. Mitchell,et al.  A machine learning approach to predicting protein-ligand binding affinity with applications to molecular docking , 2010, Bioinform..

[215]  Y. Yoon,et al.  Cell Therapy with Embryonic Stem Cell-Derived Cardiomyocytes Encapsulated in Injectable Nanomatrix Gel Enhances Cell Engraftment and Promotes Cardiac Repair , 2014, ACS nano.

[216]  Meir Glick,et al.  Prediction of Biological Targets for Compounds Using Multiple-Category Bayesian Models Trained on Chemogenomics Databases , 2006, J. Chem. Inf. Model..

[217]  G. Albertini,et al.  Polyglycolic acid-polylactic acid scaffold response to different progenitor cell in vitro cultures: a demonstrative and comparative X-ray synchrotron radiation phase-contrast microtomography study. , 2014, Tissue engineering. Part C, Methods.

[218]  R. Zare,et al.  Combining Desorption Electrospray Ionization Mass Spectrometry Imaging and Machine Learning for Molecular Recognition of Myocardial Infarction. , 2018, Analytical chemistry.

[219]  K. Poss,et al.  Cardiac regeneration strategies: Staying young at heart , 2017, Science.

[220]  N. Frangogiannis The Functional Pluralism of Fibroblasts in the Infarcted Myocardium. , 2016, Circulation research.

[221]  Ulyana Shimanovich,et al.  Fibrous Protein Self‐Assembly in Biomimetic Materials , 2018, Advanced materials.

[222]  Thomas Eschenhagen,et al.  Cardiac tissue engineering: state of the art. , 2014, Circulation research.

[223]  Dmitrii Bychkov,et al.  Deep learning based tissue analysis predicts outcome in colorectal cancer , 2018, Scientific Reports.

[224]  D. Mooney,et al.  Presentation of BMP-2 mimicking peptides in 3D hydrogels directs cell fate commitment in osteoblasts and mesenchymal stem cells. , 2014, Biomacromolecules.

[225]  D. Zeugolis,et al.  Influence of Nonsulfated Polysaccharides on the Properties of Electrospun Poly(lactic-co-glycolic acid) Fibers. , 2017, ACS biomaterials science & engineering.

[226]  Á. Carracedo,et al.  Prevalence of HCM and long QT syndrome mutations in young sudden cardiac death-related cases , 2011, International Journal of Legal Medicine.

[227]  Daniel C Bartos,et al.  The cardiomyocyte molecular clock, regulation of Scn5a, and arrhythmia susceptibility. , 2013, American journal of physiology. Cell physiology.

[228]  Howon Lee,et al.  Ultralight, ultrastiff mechanical metamaterials , 2014, Science.

[229]  C. Indolfi,et al.  Kitcre knock-in mice fail to fate-map cardiac stem cells , 2018, Nature.

[230]  X. Cui,et al.  NIPAM-based Microgel Microenvironment Regulates the Therapeutic Function of Cardiac Stromal Cells. , 2018, ACS applied materials & interfaces.

[231]  Fen Chen,et al.  Biomimetic approach to cardiac tissue engineering: oxygen carriers and channeled scaffolds. , 2006, Tissue engineering.

[232]  J. L. Mego,et al.  THE USE OF FORMALDEHYDE-TREATED 131I-ALBUMIN IN THE STUDY OF DIGESTIVE VACUOLES AND SOME PROPERTIES OF THESE PARTICLES FROM MOUSE LIVER , 1967, The Journal of cell biology.

[233]  Areum Jo,et al.  Efficient Mitochondrial Genome Editing by CRISPR/Cas9 , 2015, BioMed research international.

[234]  Nicholas A Peppas,et al.  Hydrogels and Scaffolds for Immunomodulation , 2014, Advanced materials.

[235]  Zhiqiang Su,et al.  Fabrication of graphene–biomacromolecule hybrid materials for tissue engineering application , 2017 .

[236]  G. Vunjak‐Novakovic,et al.  Paracrine Effects of Mesenchymal Stromal Cells Cultured in Three-Dimensional Settings on Tissue Repair. , 2017, ACS biomaterials science & engineering.

[237]  Fei Wang,et al.  Deep learning for healthcare: review, opportunities and challenges , 2018, Briefings Bioinform..

[238]  Wei Fan,et al.  Self-assembly of fibronectin mimetic peptide-amphiphile nanofibers. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[239]  R. Bolli,et al.  Clinical Studies of Cell Therapy in Cardiovascular Medicine: Recent Developments and Future Directions , 2018, Circulation research.

[240]  Xuesi Chen,et al.  Co-electrospun blends of PLGA, gelatin, and elastin as potential nonthrombogenic scaffolds for vascular tissue engineering. , 2011, Biomacromolecules.