Mini-hearts for disease modeling and drug testing – process optimization versus biological functionality

Frontiers in Bioengineering and Biotechnology, vol. 13, pp. 1719533

Abstract

animal studies fail to fully recapitulate human cardiac physiology, highlighting the urgent need for more relevant human-based models. Engineered three-dimensional cardiac systems - including organoids, engineered heart tissues, and heart-on-chip platforms offer promising alternatives, providing structural and functional insights into cardiac biology. However, a critical limitation of these models is their inability to perform fluid pumping and relaxation, which together define fundamental heart function. Engineered cardiac chambers have emerged to address this gap, enabling physiologically relevant pressure-volume measurements and capturing both contractile and diastolic dynamics that mimic aspects of native cardiac hemodynamics. This mini-review examines the current state of engineered cardiac chambers and highlights their main design features. We discuss their applications in disease modeling and drug testing, and outline key factors influencing the optimization of these models, including balancing biological fidelity with process efficiency through modular design principles. Overall, engineered cardiac chambers represent a unique, powerful platform to improve mechanistic understanding of cardiac disease, offering significant potential to advance cardiovascular research and therapeutic development.

Authors 4

1. Jana Hecking

   University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, Department of Bio Engineering Technologies, TechMed Centre, University of Twente, Enschede, Netherlands

2. Mariel Cano-Jorge

   University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, Department of Bio Engineering Technologies, TechMed Centre, University of Twente, Enschede, Netherlands

3. Robert C. J. J. Passier Aachen Department of Anatomy and Embryology

   Leiden University · Leiden University Medical Center · University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, Department of Bio Engineering Technologies, TechMed Centre, University of Twente, Enschede, Netherlands

   Department of Anatomy and Embryology, Leiden University Medical Centre, Leiden, Netherlands

4. José M. Rivera‐Arbeláez corresponding

   Max Planck University of Twente Center for Complex Fluid Dynamics · University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, Department of Bio Engineering Technologies, TechMed Centre, University of Twente, Enschede, Netherlands

   BIOS Lab-on-a-Chip Group, MESA+ Institute for Nanotechnology, Max Planck Institute for Complex Fluid Dynamics, University of Twente, Enschede, Netherlands