Robust T-tubulation and maturation of cardiomyocytes using tissue-engineered epicardial mimetics.

Journal Article (Journal Article)

Complex three-dimensional (3-D) heart structure is an important determinant of cardiac electrical and mechanical function. In this study, we set to develop a versatile tissue-engineered system that can promote important aspects of cardiac functional maturation and reproduce variations in myofiber directions present in native ventricular epicardium. We cultured neonatal rat cardiomyocytes within a 3-D hydrogel environment using microfabricated elastomeric molds with hexagonal posts. By varying individual post orientations along the directions derived from diffusion tensor magnetic resonance imaging (DTMRI) maps of human ventricle, we created large (2.5 × 2.5 cm(2)) 3-D cardiac tissue patches with cardiomyocyte alignment that replicated human epicardial fiber orientations. After 3 weeks of culture, the advanced structural and functional maturation of the engineered 3-D cardiac tissues compared to age-matched 2-D monolayers was evident from: 1) the presence of dense, aligned and electromechanically-coupled cardiomyocytes, quiescent fibroblasts, and interspersed capillary-like structures, 2) action potential propagation with near-adult conduction velocity and directional dependence on local cardiomyocyte orientation, and 3) robust formation of T-tubules aligned with Z-disks, co-localization of L-type Ca(2+) channels and ryanodine receptors, and accelerated Ca(2+) transient kinetics. This biomimetic tissue-engineered platform can enable systematic in vitro studies of cardiac structure-function relationships and promote the development of advanced tissue engineering strategies for cardiac repair and regeneration.

Full Text

Duke Authors

Cited Authors

  • Bian, W; Badie, N; Himel, HD; Bursac, N

Published Date

  • April 2014

Published In

Volume / Issue

  • 35 / 12

Start / End Page

  • 3819 - 3828

PubMed ID

  • 24508078

Pubmed Central ID

  • PMC3952205

Electronic International Standard Serial Number (EISSN)

  • 1878-5905

International Standard Serial Number (ISSN)

  • 0142-9612

Digital Object Identifier (DOI)

  • 10.1016/j.biomaterials.2014.01.045


  • eng