A highly versatile biopolymer‐based platform for the maturation of human pluripotent stem cell‐derived cardiomyocytes enables functional analysis in vitro and 3D printing of heart patches

Abstract

Human pluripotent stem cell‐derived cardiomyocytes (hPSC‐CMs) represent a valuable tool for in vitro modeling of the cardiac niche and possess great potential in tissue engineering applications. However, conventional polystyrene‐based cell culture substrates have adverse effects on cardiomyocytes in vitro due to the stress applied by a stiff substrate on contractile cells. Ultra‐high viscosity alginates offer a unique versatility as tunable substrates for cardiac cell cultures due to their biocompatibility, flexible biofunctionalization, and stability. In this work, we analyzed the effect of alginate substrates on hPSC‐CM maturity and functionality. Alginate substrates in high‐throughput compatible culture formats fostered a more mature gene expression and enabled the simultaneous assessment of chronotropic and inotropic effects upon beta‐adrenergic stimulation. Furthermore, we produced 3D‐printed alginate scaffolds with differing mechanical properties and plated hPSC‐CMs on the surface of these to create Heart Patches for tissue engineering applications. These exhibited synchronous macro‐contractions in concert with more mature gene expression patterns and extensive intracellular alignment of sarcomeric structures. In conclusion, the combination of biofunctionalized alginates and human cardiomyocytes represents a valuable tool for both in vitro modeling and regenerative medicine, due to its beneficial effects on cardiomyocyte physiology, the possibility to analyze cardiac contractility, and its applicability as Heart Patches.

Applications, advancements, and challenges of 3D bioprinting in organ transplantation

“…A team of researchers at the University of Erlangen-Nuremberg in Germany made remarkable achievements in the field of 3D printing technology. 105 They successfully created a miniature heart chamber (the chamber at the bottom of the heart) that could beat autonomously for at least three months. Although there have been many breakthroughs in 3D printing in recent years, the fine structure and complex function of the myocardium have not been fully simulated.…”