PhD Student Universidad Politécnica de Valencia Valencia, Comunidad Valenciana, Spain
Abstract: Diseases affecting the left ventricle pose a major challenge in cardiovascular research due to their high morbidity and mortality worldwide. Studying these conditions using animal models is limited by substantial electrophysiological and mechanical differences between animal and human hearts. To overcome these limitations, novel in vitro models of the left ventricle have been developed using 3D bioprinting techniques and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), providing a promising platform to investigate disease mechanisms, as well as growth and remodeling responses. To address this challenge, we have developed tissue-engineered cardiac ventricles (TECVs) designed as truncated ellipsoids (10 mm length, 10 mm diameter, 0.5 mm thickness) optimized for bioprinting. A bioink of methacrylated gelatin and collagen embedded with hiPSC-CMs was used for fabrications. Constructs were cultured for six weeks, monitoring contractility and cardiac marker expression. However, TECVs showed weak contractions, with cardiomyocytes forming isolated beating clusters instead of a connected network. To improve this, we incorporated human cardiac fibroblasts (hCFs), known to enhance cardiomyocyte maturity and contractility. We bioprinted cardiac patches (5 × 5 × 0.8 mm) with and without hCFs and monitored them at 2, 4, and 6 weeks. Patches with hCFs exhibited stronger contractions and better sarcomere organization, as shown by sarcomeric α-actinin and cardiac troponin T immunostaining. Additionally, we aimed to recreate pressure-volume loops in TECVs, key indicators of cardiac function not easily assessed in other 3D models. To achieve this, we are developing a novel closed-chamber pressure-generator TECV, for which we are also assessing cytocompatibility of different silicones used at the base. Our findings highlight the potential of bioengineered left ventricular models in cardiac disease research. Including hCFs significantly improved contractility and tissue organization, emphasizing the role of multicellular interactions. Further optimization, including pressure-volume assessments, will enhance their physiological relevance, paving the way for advanced disease modeling and therapeutic testing.
Funding Source: Funded by the European Union (ERC Starting Grant G-Cyberheart, agreement 101039349)
