A human engineered mini-heart platform for mimicking ventricular pump function

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

Abstract Engineered cardiac tissue models for in vitro physiological studies often fail to replicate the pump function of the heart. Despite promising advancements, the use of engineered cardiac chambers is often hindered by complex fabrication processes and invasive characterization techniques. Here, we engineered a human cardiac chamber, referred to as a ‘mini-heart’, by employing a novel sacrificial molding approach within a customized bioreactor. The mini-heart’s pumping capability was confirmed through optical recording of fluid displacement at the engineered tissue inlet, enabling the non-invasive acquisition of hemodynamic parameters such as stroke volume, stroke work, ejection fraction, and developed pressure. Morphological analysis of the engineered tissues revealed organized sarcomeres and extracellular matrix self-determination, highlighting the advantage of our degradable mold technology. Additionally, we have measured calcium transients during both spontaneous and electrically-paced beating, and observed a positive inotropic response to the β-adrenergic agonist drug isoproterenol. Altogether, our biomimicking engineered tissue platform provides a robust tool for exploring cardiac pressure-volume dynamics, thereby facilitating complex disease modelling and drug screening applications in vitro .

Authors 9

1. Marcelo C. Ribeiro
   Affiliation as printed

   River BioMedics;

   River BioMedics

2. Mariel Cano-Jorge

   University of Twente

   Affiliation as printed

   University of Twente;

   University of Twente

3. Simone A. ten Den

   University of Twente

   Affiliation as printed

   University of Twente;

   University of Twente

4. Danique Snippert

   University of Twente

   Affiliation as printed

   University of Twente;

   University of Twente

5. Marcel Karperien

   University of Twente

   Affiliation as printed

   University of Twente;

   University of Twente

6. Tom Kamperman
   Affiliation as printed

   IamFluidics BV;

   IamFluidics BV

7. Guillaume Pierre René Lajoinie

   University of Twente

   Affiliation as printed

   Univeristy ofTwente;

   Univeristy ofTwente

8. Michel Versluis

   University of Twente

   Affiliation as printed

   University of Twente;

   University of Twente

9. Robert C. J. J. Passier corresponding Aachen

   Leiden University · Leiden University Medical Center · University of Twente

   Affiliation as printed

   University of Twente; Leiden University Medical Centre

   Leiden University Medical Centre

   University of Twente