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

doi:10.1016/j.isci.2022.104297

Bizonal cardiac engineered tissues with differential maturation features in a mid-throughput multimodal bioreactor

iScience. 2022 Apr 26;25(5):104297. doi: 10.1016/j.isci.2022.104297. eCollection 2022 May 20.

Authors

Alessia Pisanu^{1

2}, Gregory Reid^{1

2}, Deborah Fusco^{1

2}, Antonio Sileo^{1

2}, Diana Robles Diaz^{1

2}, Hadi Tarhini³, Giovanni Putame³, Diana Massai³, Giuseppe Isu^{1

2}, Anna Marsano^{1

2}

Affiliations

¹ Department of Biomedicine, University of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
² Department of Surgery, University Hospital of Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
³ PolitoBIOMed Lab, Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Turin, Italy.

Abstract

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.

Keywords: Bioengineering; Biological sciences; Biotechnology; Cell biology; Tissue engineering.