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Updated: Mar 9, 2026

3D Human Myocardial Tissue Generation Using Melt Electrospinning Writing of Polycaprolactone Scaffolds and hiPSC-Derived Cardiac Cells
Published on: March 28, 2025
Myocardial Tissue Engineering With Cells Derived From Human-Induced Pluripotent Stem Cells and a Native-Like,
Ling Gao1, Molly E Kupfer1, Jangwook P Jung1
1From the Department of Biomedical Engineering, School of Medicine, School of Engineering, University of Alabama at Birmingham (L.G., V.G.F., J.Z.); Department of Biomedical Engineering, University of Minnesota, Twin Cities, Minneapolis (M.E.K., J.P.J., L.Y., P.Z., B.T.F., B.M.O.); and Department of Biomedical Engineering, University of Wisconsin, Madison (Y.D.S., Q.T., V.A., P.J.C.).
Rationale:
Conventional 3-dimensional (3D) printing techniques cannot produce structures of the size at which individual cells interact.
Objective:
Here, we used multiphoton-excited 3D printing to generate a native-like extracellular matrix scaffold with submicron resolution and then seeded the scaffold with cardiomyocytes, smooth muscle cells, and endothelial cells that had been differentiated from human-induced pluripotent stem cells to generate a human-induced pluripotent stem cell-derived cardiac muscle patch (hCMP), which was subsequently evaluated in a murine model of myocardial infarction.
Methods And Results:
The scaffold was seeded with ≈50 000 human-induced pluripotent stem cell-derived cardiomyocytes, smooth muscle cells, and endothelial cells (in a 2:1:1 ratio) to generate the hCMP, which began generating calcium transients and beating synchronously within 1 day of seeding; the speeds of contraction and relaxation and the peak amplitudes of the calcium transients increased significantly over the next 7 days. When tested in mice with surgically induced myocardial infarction, measurements of cardiac function, infarct size, apoptosis, both vascular and arteriole density, and cell proliferation at week 4 after treatment were significantly better in animals treated with the hCMPs than in animals treated with cell-free scaffolds, and the rate of cell engraftment in hCMP-treated animals was 24.5% at week 1 and 11.2% at week 4.
Conclusions:
Thus, the novel multiphoton-excited 3D printing technique produces extracellular matrix-based scaffolds with exceptional resolution and fidelity, and hCMPs fabricated with these scaffolds may significantly improve recovery from ischemic myocardial injury.

