FRESH 3D bioprinting a contractile heart tube using human stem cell-derived cardiomyocytes

Biofabrication. 2022 Mar 16;14(2):10.1088/1758-5090/ac58be. doi: 10.1088/1758-5090/ac58be.

Abstract

Here we report the 3D bioprinting of a simplified model of the heart, similar to that observed in embryonic development, where the heart is a linear tube that pumps blood and nutrients to the growing embryo. To this end, we engineered a bioinspired model of the human heart tube using freeform reversible of embedding of suspended hydrogels 3D bioprinting. The 3D bioprinted heart tubes were cellularized using human stem cell-derived cardiomyocytes and cardiac fibroblasts and formed patent, perfusable constructs. Synchronous contractions were achieved ∼3-4 days after fabrication and were maintained for up to a month. Immunofluorescent staining confirmed large, interconnected networks of sarcomeric alpha actinin-positive cardiomyocytes. Electrophysiology was assessed using calcium imaging and demonstrated anisotropic calcium wave propagation along the heart tube with a conduction velocity of ∼5 cm s-1. Contractility and function was demonstrated by tracking the movement of fluorescent beads within the lumen to estimate fluid displacement and bead velocity. These results establish the feasibility of creating a 3D bioprinted human heart tube and serve as an initial step towards engineering more complex heart muscle structures.

Keywords: FRESH; bioprinting; engineered heart tissue; heart muscle; heart tube.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bioprinting* / methods
  • Humans
  • Hydrogels / chemistry
  • Myocytes, Cardiac
  • Printing, Three-Dimensional
  • Stem Cells
  • Tissue Engineering / methods
  • Tissue Scaffolds / chemistry

Substances

  • Hydrogels