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 human and non-human hearts. To overcome this, novel in vitro
models of the left ventricle have been developed using 3D bioprinting techniques and
hiPSC-CMs, providing a platform to investigate disease mechanisms, as well as growth
and remodeling responses. To address this challenge, tissue-engineered cardiac
ventricles (TECVs) were designed as truncated ellipsoids. Constructs were cultured for
six weeks, monitoring contractility and cardiac marker expression. However, TECVs
showed weak contractions as hiPSCs-CMs formed isolated beating clusters instead of
a connected network. To improve this, human cardiac fibroblasts (hCFs) were
incorporated, which enhance hiPSCs-CMs maturity and contractility. Cardiac patches
were bioprinted with and without hCFs and monitored them up to 6 weeks. Patches
with hCFs exhibited stronger contractions and better sarcomere organization.
Additionally, we aimed to recreate pressure-volume loops in TECVs, key indicators of
cardiac function. To achieve this, a novel closed-chamber pressure-generator TECV
was developed. Our findings highlight the potential of hTECVs in cardiac disease
research. Further optimization, including pressure-volume assessments, will enhance
their physiological relevance.
