The arrhythmogenic effect of self-assembling nanopeptide hydrogel scaffolds on neonatal mouse cardiomyocytes.
The chaotic spatial disarray due to extracellular matrix expansion disrupts cardiomyocytes interaction and causes arrhythmia. We hypothesized that disordered nanopeptide scaffolds can mimic the chaotic spatial disarray related to cardiac fibrosis and have arrhythmogenic effects on cardiomyocytes. Primary mouse cardiomyocytes were cultured in 2D traditional and 3D nanopeptide hydrogel scaffold systems. Cardiomyocytes in 3D scaffolds showed irregular spontaneous contractile activity as compared with 2D culture controls. Calcium fluorimetric imaging revealed that basal intracellular calcium level increased 1.42-fold in cardiomyocytes cultured in the 3D scaffold, in vitro. The mRNA levels of sarcoplasmic reticulum calcium transport ATPase, ryanodine 2 receptor and connexin 43 elevated 2.14-fold, 2.33-fold and 2.62-fold in 3D compared with 2D. Immunofluorescence imaging revealed lateralization of the distribution of connexin 43 in 3D group. These findings suggest that 3D hydrogel culture system provides a model for the development of cardiac dysrhythmia. These limitations should be considered during cardiac tissue engineering.


BACKGROUND
This team of scientists has established a unique 3D hydrogel culture system as a model for the development of cardiac dysrhythmia.
Division of Cardiology, Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei City, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Yu-Wei
YW
Chiu
Institute of Pharmacology, School of Medicine, National Taiwan University, Taipei, Taiwan.
Wen-Pin
WP
Chen
Division of Cardiology, Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei City, Taiwan.
Chi-Chang
CC
Su
Division of Cardiology, Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei City, Taiwan.
Yen-Chia
YC
Lee
Division of Cardiology, Department of Internal Medicine, Far-Eastern Memorial Hospital, New Taipei City, Taiwan.
Pei-Hsing
PH
Hsieh
Graduate Institute of Clinical Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: ylho@ntu.edu.tw.
Yi-Lwun
YL
Ho
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects*; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D054457:Tissue Scaffolds / Q000737:chemistry*
D010455:Peptides; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
Arrhythmia; Cardiomyocyte; Connexin 43; Nanopeptide scaffold