Microfabricated perfusable cardiac biowire: a platform that mimics native cardiac bundle

Area of Science:

• Cardiovascular Research
• Tissue Engineering
• Biomedical Engineering

Background:

• Current 3D cardiac tissue models lack the complex architecture of native cardiac bundles and capillaries.
• Accurate in vitro models are crucial for effective pre-clinical drug development and testing.

Purpose of the Study:

• To design and validate a microfabricated bioreactor for generating perfusable, electrically stimulated 3D cardiac tissue constructs (biowires).
• To assess the utility of this platform for evaluating pharmacological effects on cardiac tissue in vitro.

Main Methods:

• Fabrication of a microfluidic bioreactor using polytetrafluoroethylene (PTFE) tubing.
• Generation of cardiac biowires using neonatal rat and human embryonic stem cell (hESC)-derived cardiomyocytes.
• Integration of electrical field stimulation and perfusion capabilities for nitric oxide (NO) drug testing.

Main Results:

• Successfully generated perfusable cardiac biowires with aligned cardiomyocytes.
• Demonstrated NO's impact on cardiomyocyte beating rate and cytoskeletal integrity.
• Electrical stimulation enhanced cardiomyocyte phenotype, improving contractile apparatus organization and mechanical/electrical properties.

Conclusions:

• The microfabricated bioreactor platform enables the creation of physiologically relevant 3D cardiac tissue models.
• This platform facilitates in vitro assessment of drug effects on cardiac bundles via perfusion, offering improved pre-clinical testing accuracy.