Engineering microenvironment for human cardiac tissue assembly in heart-on-a-chip platform

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Stem Cell Biology

Background:

• Organ-on-a-chip systems offer advanced drug screening and disease modeling.
• Human stem cell-derived cardiomyocytes are key building blocks for these models.
• Achieving adult-like phenotypes requires precise control over the cardiomyocyte microenvironment.

Purpose of the Study:

• To investigate the impact of microenvironmental factors on cardiac tissue assembly.
• To optimize conditions for mature human pluripotent stem cell-derived cardiac tissues.
• To develop a functional heart-on-a-chip model for studying cardiac tissue development.

Main Methods:

• Utilized a novel, open-access heart-on-a-chip system for non-invasive monitoring.
• Investigated effects of cell seeding density, non-myocyte populations, hydrogel types, and electrical conditioning.
• Assessed structural and functional assembly of human pluripotent stem cell-derived cardiac tissues.

Main Results:

• Identified specific microenvironmental conditions promoting cardiac tissue maturation.
• Demonstrated the formation of functional cardiac tissues with adult-like properties.
• Achieved hallmarks of mature human myocardium, including positive force-frequency relationship and post-rest potentiation.

Conclusions:

• Microenvironmental engineering is crucial for developing predictive cardiac tissue models.
• Optimized heart-on-a-chip conditions yield functional tissues mimicking adult human myocardium.
• This platform advances drug screening and disease modeling for cardiovascular applications.