Development of a novel 3D cardiovascular pharmacological platform for in vitro drug screening

Drug development is costly and risky, with preclinical evaluation typically relying on expensive, low-throughput animal models or fast, profitable two-dimensional (2D) cell cultures, unable to mimic the 3D in vivo environment. To compensate for the lack of 3D extracellular matrix (ECM) and its cell interactions, in vitro 3D models have been advanced. Due to their biocompatibility and ability to simulate the ECM, hydrogels are reliable in shifting in vitro models from 2D to 3D microenvironments, and useful also in the settings of drug screening. This project aims to develop a 3D cardiovascular tissue-engineered model as a pharmacological platform alternative combining a hydrogel derived from decellularized heart and human endothelial cells. Drugs with known effects on these cells can be used to validate the platform in comparison to a 2D standard cell culture. Cardiac specimens were isolated from the porcine left ventricle and submitted to an optimized decellularization method using osmotic shock, detergents, and mechanical agitation. Lyophilization, pulverization, and digestion were applied to the decellularized myocardial scaffold to generate an organ-specific hydrogel. Histological and immunofluorescence analyses confirmed ECM preservation and complete removal of cell content. The assembly of a 3D bioengineered tissue is ongoing, and its validation will be realized.