Bizonal cardiac engineered tissues with differential maturation features in a mid-throughput multimodal bioreactor
Alessia Pisanu,
Gregory Reid,
Deborah Fusco,
Antonio Sileo,
Diana Robles Diaz,
Hadi Tarhini,
Giovanni Putame,
Diana Massai,
Giuseppe Isu,
Anna Marsano
Affiliations
Alessia Pisanu
Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland; Department of Surgery, University Hospital of Basel, Hebelstrasse 20, 4031 Basel, Switzerland
Gregory Reid
Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland; Department of Surgery, University Hospital of Basel, Hebelstrasse 20, 4031 Basel, Switzerland
Deborah Fusco
Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland; Department of Surgery, University Hospital of Basel, Hebelstrasse 20, 4031 Basel, Switzerland
Antonio Sileo
Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland; Department of Surgery, University Hospital of Basel, Hebelstrasse 20, 4031 Basel, Switzerland
Diana Robles Diaz
Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland; Department of Surgery, University Hospital of Basel, Hebelstrasse 20, 4031 Basel, Switzerland
Hadi Tarhini
PolitoBIOMed Lab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy
Giovanni Putame
PolitoBIOMed Lab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy
Diana Massai
PolitoBIOMed Lab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy
Giuseppe Isu
Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland; Department of Surgery, University Hospital of Basel, Hebelstrasse 20, 4031 Basel, Switzerland
Anna Marsano
Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland; Department of Surgery, University Hospital of Basel, Hebelstrasse 20, 4031 Basel, Switzerland; Corresponding author
Summary: Functional three-dimensional (3D) engineered cardiac tissue (ECT) models are essential for effective drug screening and biological studies. Application of physiological cues mimicking those typical of the native myocardium is known to promote the cardiac maturation and functionality in vitro. Commercially available bioreactors can apply one physical force type at a time and often in a restricted loading range. To overcome these limitations, a millimetric-scale microscope-integrated bioreactor was developed to deliver multiple biophysical stimuli to ECTs. In this study, we showed that the single application of auxotonic loading (passive) generated a bizonal ECT with a unique cardiac maturation pattern. Throughout the statically cultured constructs and in the ECT region exposed to high passive loading, cardiomyocytes predominantly displayed a round morphology and poor contractility ability. The ECT region with a low passive mechanical stimulation instead showed both rat- and human-origin cardiac cell maturation and organization, as well as increased ECT functionality.
