4.7 Article

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

Journal

BIOFABRICATION
Volume 14, Issue 2, Pages -

Publisher

IOP Publishing Ltd
DOI: 10.1088/1758-5090/ac58be

Keywords

heart tube; bioprinting; engineered heart tissue; heart muscle; FRESH

Funding

  1. Office of Naval Research [N00014-17-1-2566]
  2. Food & Drug Administration [R01FD006582]
  3. Dowd Fellowship
  4. Carnegie Mellon Presidential Fellowship
  5. Additional Ventures Cures Collaborative

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This study demonstrates the 3D bioprinting of a simplified heart model resembling embryonic development. The engineered heart tubes were cellularized and showed synchronous contractions similar to natural heart beats. These findings establish the feasibility of creating 3D bioprinted human heart tubes and open the door for engineering more complex heart muscle structures.
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 similar to 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 similar to 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.

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