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Generation of Aligned Functional Myocardial Tissue Through Microcontact Printing
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Engineering aligned human cardiac muscle using developmentally inspired fibronectin micropatterns.

Ivan Batalov1, Quentin Jallerat2, Sean Kim2

  • 1Department of Materials Science and Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, Pennsylvania, 15213, USA.

Scientific Reports
|June 2, 2021
PubMed
Summary

Engineered cardiac tissues using biomimetic patterns revealed that cell-cell and cell-extracellular matrix (ECM) interactions guide cardiomyocyte alignment, crucial for developing organized heart muscle.

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Area of Science:

  • Biomaterials Science
  • Cardiovascular Biology
  • Stem Cell Biology

Background:

  • Cardiac tissue engineering aims to replicate the native heart's complex cellular architecture.
  • Understanding cardiomyocyte organization is key for developing functional cardiac constructs.
  • The embryonic heart's extracellular matrix (ECM) provides critical cues for cardiac development.

Purpose of the Study:

  • To engineer cardiac tissues using biomimetic micropatterns.
  • To investigate cell-cell and cell-ECM interactions driving cardiomyocyte alignment.
  • To identify factors influencing anisotropic cardiac tissue formation in vitro.

Main Methods:

  • Created biomimetic micropatterns based on embryonic chick heart fibronectin.
  • Engineered 2D cardiac tissues using embryonic chick and human induced pluripotent stem cell-derived cardiomyocytes.
  • Assessed cardiomyocyte alignment on micropatterns with varying fibronectin line widths.
  • Investigated the role of N-cadherin, cardiac fibroblasts, and T3 hormone.

Main Results:

  • Embryonic chick cardiomyocytes exhibited density-dependent alignment on biomimetic micropatterns, mediated by N-cadherin.
  • Human cardiomyocytes showed density-dependent alignment but less organization.
  • Addition of cardiac fibroblasts and T3 hormone improved human cardiomyocyte alignment.
  • Both cell-cell and cell-ECM interactions are vital for aligned myocardium formation.

Conclusions:

  • Biomimetic micropatterns can guide cardiomyocyte organization in vitro.
  • Cardiomyocyte maturation, cell-cell, cell-fibroblast, and cell-ECM interactions influence engineered cardiac tissue anisotropy.
  • Findings offer insights into cardiogenesis mechanisms in vivo.