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

Cardiovascular Research

Abstract

AIM: 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 chamber-like human cardiac model with pumping function, referred to as a 'mini-heart', by employing a novel sacrificial molding approach within a customized bioreactor. METHODS AND RESULTS: Human pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts were embedded in a fibrin mix and casted around two gelatin bodies within a customized bioreactor. After fibrin polymerization, thermal degradation of gelatin was induced to obtain a single-inlet cardiac chamber coupled to a glass capillary inlet.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. CONCLUSIONS: We present a biomimetic, chamber-like human cardiac model with intrinsic pumping function that enables non-invasive functional assessment of cardiac hemodynamics in vitro.

Authors 9

1. Marcelo C. Ribeiro

   University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, Department of BioEngineering Technologies,Cardiovascular Health Technology Center, TechMed Centre, University of Twente , Enschede ,

   River BioMedics , Enschede ,

2. Mariel Cano-Jorge

   University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, Department of BioEngineering Technologies,Cardiovascular Health Technology Center, TechMed Centre, University of Twente , Enschede ,

3. Simone A. ten Den

   University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, Department of BioEngineering Technologies,Cardiovascular Health Technology Center, TechMed Centre, University of Twente , Enschede ,

4. Danique Snippert

   University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, Department of BioEngineering Technologies,Cardiovascular Health Technology Center, TechMed Centre, University of Twente , Enschede ,

5. Marcel Karperien

   University of Twente

   Affiliation as printed

   Developmental BioEngineering, Department of BioEngineering Technologies, TechMed Centre, University of Twente , Enschede ,

6. Tom Kamperman
   Affiliation as printed

   IamFluidics B.V , Enschede ,

7. Guillaume Pierre René Lajoinie

   University of Twente

   Affiliation as printed

   Physics of Fluids Group, TechMed Centre, University of Twente , Enschede ,

8. Michel Versluis

   University of Twente

   Affiliation as printed

   Physics of Fluids Group, TechMed Centre, University of Twente , Enschede ,

9. Robert C. J. J. Passier corresponding Aachen Department of Anatomy and Embryology

   Leiden University · Leiden University Medical Center · University of Twente

   Affiliation as printed

   Applied Stem Cell Technologies, Department of BioEngineering Technologies,Cardiovascular Health Technology Center, TechMed Centre, University of Twente , Enschede ,

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