PEER-REVIEWED PUBLICATION

2019

A platform for generation of chamber-specific cardiac tissues and disease modelling

Zhao Y, Rafatian N, et al.

Cell

University of Toronto, University Health Network, Medical College of Wisconsin, Columbia University, McGill University, York University, Toronto General Research Institute

Canada, United States

RESEARCH SUMMARY

This study presents the Biowire II platform, a micro scale mechanical testing cardiac tissue system that enables long-term culture and non-invasive, online measurement of passive tension, active force, contractile dynamics, and calcium transients under electrical pacing. Using directed differentiation plus chronic electrical conditioning, the authors generated electrophysiologically distinct atrial and ventricular tissues with chamber-specific gene expression and drug responses, and engineered heteropolar atrio-ventricular tissues with spatially confined responses to serotonin and ranolazine. The platform also supported months-long conditioning (up to ~8 months) to model polygenic cardiac disease (left ventricular hypertrophy) from patient-derived iPSCs.

A customized CellScale MicroSquisher was used to generate force–displacement calibration curves for the elastic POMaC wires that serve as the platform’s built-in force-sensing elements. In culture media, a modified tungsten probe with custom tips displaced the wires while force and displacement were recorded, producing calibration relationships used to convert measured wire deflection into quantitative tissue forces (passive tension and active force) during beating and drug testing. This CellScale-based mechanical calibration step was essential to the study because it enabled the platform’s core capability: non-invasive, repeated force readouts over time without removing or destroying tissues.

AUTHORS

Yimu Zhao; Naimeh Rafatian; Nicole T. Feric; Brian Cox; Roozbeh Aschar-Sobbi; Erika Yan Wang; Praful Aggarwal; Boyang Zhang; Genevieve Conant; Kacey Aric Pahnke; Stephanie Protze; Jee Hoon Lee; Locke Davenport Huyer; Danica Jekic; Anastasia Wickeler; Hani Naguib; Gordon M. Keller; Gordana Vunjak-Novakovic; Ulrich Broeckel; Peter H. Backx; Milica Radisic.

PUBLICATION DETAILS

JOURNAL

Cell

YEAR

2019

INSTITUTIONS

University of Toronto, University Health Network, Medical College of Wisconsin, Columbia University, McGill University, York University, Toronto General Research Institute

COUNTRIES

Canada, United States

INSTRUMENT USED

Custom

TESTING METHODS

Indentation TestingMicro-Mechanical Testing

RESEARCH APPLICATIONS

Cardiac Tissue Engineering & MechanicsDrug Screening & Drug Delivery MechanicsMechanotransductionOrgan-On-A-Chip SystemsStem Cell Mechanobiology

Related Publications:

Instrument Used:

Year:

Testing Method:

Research Application:

Country:

Introducing a Custom-Designed Volume-Pressure Machine for Novel Measurements of Whole Lung Organ Viscoelasticity and Direct Comparisons Between Positive- and Negative-Pressure Ventilation

Sattari S, Mariano CA, et al.

Frontiers in Bioengineering and Biotechnology

Custom

Hydrated and Temperature Controlled TestingPressure TestingStress Relaxation TestingViscoelastic & Time-Dependent Testing

Fibrosis & Tissue RemodelingLung and Pleural Tissue BiomechanicsMechanotransduction

2020