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

AbstractHuman 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.