title: Modeling the Human Scarred Heart In Vitro: Toward New Tissue Engineered Models.
abstract: Cardiac remodeling is critical for effective tissue healing, however, excessive production and deposition of extracellular matrix components contribute to scarring and failing of the heart. Despite the fact that novel therapies have emerged, there are still no lifelong solutions for this problem. An urgent need exists to improve the understanding of adverse cardiac remodeling in order to develop new therapeutic interventions that will prevent, reverse, or regenerate the fibrotic changes in the failing heart. With recent advances in both disease biology and cardiac tissue engineering, the translation of fundamental laboratory research toward the treatment of chronic heart failure patients becomes a more realistic option. Here, the current understanding of cardiac fibrosis and the great potential of tissue engineering are presented. Approaches using hydrogel-based tissue engineered heart constructs are discussed to contemplate key challenges for modeling tissue engineered cardiac fibrosis and to provide a future outlook for preclinical and clinical applications.
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, 3584CX, Utrecht, The Netherlands.|Netherlands Heart Institute (ICIN), 3584CX, Utrecht, The Netherlands.
authors.forename: Janine C
authors.initials: JC
authors.lastname: Deddens
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, 3584CX, Utrecht, The Netherlands.|Department of Cardiothoracic Surgery, Division Heart and Lungs, University Medical Center Utrecht, 3584CX, Utrecht, The Netherlands.|Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA.|Harvard-MIT Division of Health Sciences & Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
authors.forename: Amir Hossein
authors.initials: AH
authors.lastname: Sadeghi
authors.affiliation: Department of Cardiothoracic Surgery, Division Heart and Lungs, University Medical Center Utrecht, 3584CX, Utrecht, The Netherlands.|UMC Utrecht Regenerative Medicine Center, University Medical Center Utrecht, 3584CT, Utrecht, The Netherlands.
authors.forename: Jesper
authors.initials: J
authors.lastname: Hjortnaes
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, 3584CX, Utrecht, The Netherlands.|UMC Utrecht Regenerative Medicine Center, University Medical Center Utrecht, 3584CT, Utrecht, The Netherlands.
authors.forename: Linda W
authors.initials: LW
authors.lastname: van Laake
authors.affiliation: Department of Cardiothoracic Surgery, Division Heart and Lungs, University Medical Center Utrecht, 3584CX, Utrecht, The Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Buijsrogge
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, 3584CX, Utrecht, The Netherlands.|Netherlands Heart Institute (ICIN), 3584CX, Utrecht, The Netherlands.|UMC Utrecht Regenerative Medicine Center, University Medical Center Utrecht, 3584CT, Utrecht, The Netherlands.
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.affiliation: Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA.|Harvard-MIT Division of Health Sciences & Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, 02115, USA.|Department of Physics, King Abdulaziz University, Jeddah, 21569, Saudi Arabia.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
authors.affiliation: Department of Cardiology, University Medical Center Utrecht, 3584CX, Utrecht, The Netherlands.|Netherlands Heart Institute (ICIN), 3584CX, Utrecht, The Netherlands.|UMC Utrecht Regenerative Medicine Center, University Medical Center Utrecht, 3584CT, Utrecht, The Netherlands.
authors.forename: Joost P G
authors.initials: JP
authors.lastname: Sluijter
mesh_terms: D005355:Fibrosis; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D023822:Tissue Engineering / Q000379:methods*
keywords: cardiac fibrosis; cardiac remodeling; cardiac tissue engineering; drug development; extracellular matrix; hydrogels