Beating heart on a chip: a novel microfluidic platform to generate functional 3D cardiac microtissues

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Tissue Engineering

Background:

• Microfluidic technology has advanced cardiac microscale models, but replicating native myocardial mechanical cues in 3D remains a challenge.
• Existing 2D models neglect complex 3D cell-cell and cell-matrix interactions crucial for cardiac function.

Purpose of the Study:

• To develop a heart-on-a-chip platform capable of applying controlled physiological uniaxial cyclic strains to 3D cell constructs.
• To create a robust and functional engineered cardiac micro-niche that mimics the native myocardial mechanical environment.

Main Methods:

• A novel heart-on-a-chip device featuring hanging posts and a pneumatic actuation system was designed to induce uniaxial cyclic strain.
• The platform was used to culture micro-engineered cardiac tissues (μECTs) from neonatal rat and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM).

Main Results:

• Stimulated μECTs exhibited superior cardiac differentiation, electrical and mechanical coupling, and increased junction complexes compared to controls.
• The cyclic strain was effectively uniaxial and uniformly transferred, promoting early synchronous beating and enhanced contractile function.
• Drug testing on hiPSC-CM constructs demonstrated the platform's utility in drug discovery, delivery, and toxicology.

Conclusions:

• The developed heart-on-a-chip platform provides a standardized, functional 3D cardiac model that recapitulates physiological mechanical stimulation.
• This advanced model holds potential for predicting hypertrophic changes and advancing cardiac research, drug development, and toxicology assessments.