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Sci Rep. 2016 Aug 30;6:32068. doi: 10.1038/srep32068.

Anisotropic engineered heart tissue made from laser-cut decellularized myocardium.

Author information

1
Department of Biomedical Engineering, Yale University, New Haven, CT 06510, USA.
2
Department of Biomedical Engineering, University of Hartford, West Hartford, CT 06117, USA.
3
Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA.
4
Yale Stem Cell Center, Yale University, New Haven, CT 06510, USA.
5
Vascular Biology and Therapeutics Program, Yale School of Medicine, New Haven, CT 06510, USA.
6
Department of Pathology, Yale University, New Haven, CT 06510, USA.
7
Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT 06510, USA.

Abstract

We have developed an engineered heart tissue (EHT) system that uses laser-cut sheets of decellularized myocardium as scaffolds. This material enables formation of thin muscle strips whose biomechanical characteristics are easily measured and manipulated. To create EHTs, sections of porcine myocardium were laser-cut into ribbon-like shapes, decellularized, and mounted in specialized clips for seeding and culture. Scaffolds were first tested by seeding with neonatal rat ventricular myocytes. EHTs beat synchronously by day five and exhibited robust length-dependent activation by day 21. Fiber orientation within the scaffold affected peak twitch stress, demonstrating its ability to guide cells toward physiologic contractile anisotropy. Scaffold anisotropy also made it possible to probe cellular responses to stretch as a function of fiber angle. Stretch that was aligned with the fiber direction increased expression of brain natriuretic peptide, but off-axis stretches (causing fiber shear) did not. The method also produced robust EHTs from cardiomyocytes derived from human embryonic stem cells and induced pluripotent stem cells (hiPSC). hiPSC-EHTs achieved maximum peak stress of 6.5 mN/mm(2) and twitch kinetics approaching reported values from adult human trabeculae. We conclude that laser-cut EHTs are a viable platform for novel mechanotransduction experiments and characterizing the biomechanical function of patient-derived cardiomyoctyes.

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