Geometrically controlled cardiac microtissues promote vascularization and reduce inflammation in vitro and in vivo

This study developed geometrically controlled human iPSC-derived cardiac microtissues as building blocks for engineered heart grafts that promote vascularization and minimize inflammatory responses. Using PDMS micromolds with defined pillar geometries, the team generated anisotropic microtissues that exhibited enhanced sarcomeric alignment, contractility, and electrical responsiveness. When implanted in the omentum of nude rats, the microtissues achieved robust engraftment, host vascular integration, and reduced macrophage-driven inflammation compared with dispersed cardiomyocytes. Proteomic and cytokine profiling revealed that microtissues suppress inflammatory pathways via YAP/TAZ downregulation and upregulate pro-angiogenic signaling (PlGF, endocan, angiopoietin-2), suggesting a mechano-biological route to improved cardiac graft integration.