Reduced Graphene Oxide Enhances the Vascular Organization and Contractile Performance of Fibrin‐Gelatin‐Based Engineered Cardiac Tissue

ABSTRACT Cardiac in vitro models are powerful tools for studying cardiac development, disease mechanisms, drug screening, and regenerative therapies. However, the available extracellular matrix substitutes do not promote optimal contractility of the embedded cardiomyocytes. This study hypothesizes that functionalizing fibrin–gelatin hydrogels with reduced graphene oxide (rGO) will significantly improve the synchronized contraction and enhance in vitro vascularization. To test this hypothesis, fibrin and fibrin–gelatin hydrogels containing different concentrations of rGO are analyzed for the mechanical properties, microstructure, prevascularization potential, and contraction behavior of the embedded cultures of cardiomyocytes (CMs), endothelial cells, and fibroblasts. In addition, the responses of the CMs to cardioactive drugs are investigated. Increasing rGO concentration enhanced the storage modulus, vascular lumen diameter, and cardiomyocyte contraction amplitude up to 0.04% (w/v) rGO in fibrin–gelatin blends, whereas higher concentrations were associated with reduced effects. Furthermore, engineered cardiac tissues show physiological responses to cardioactive drugs. Compared to classical 2D and spheroid cultures, hydrogel‐based cardiac cultures demonstrate increased cardiac‐ and vascular‐related gene expression. In conclusion, functionalizing fibrin–gelatin hydrogels with rGO is a promising cardiac tissue engineering strategy because the modified blend supports cardiac functional properties.