Cardiac Tissue Chips (CTCs) for Modeling Cardiovascular Disease.

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Regenerative Medicine

Background:

• Current cardiovascular research is limited by the absence of cell culture models that replicate the complex hemodynamic stresses of cardiac pressure-volume changes.
• Developing physiologically relevant models is crucial for advancing cardiovascular disease understanding and therapeutic strategies.

Purpose of the Study:

• To design and validate a biomimetic cardiac tissue chip (CTC) model capable of mimicking the hemodynamic loading and unloading conditions of the human heart.
• To utilize the CTC model for studying pathophysiological mechanical stresses in cardiovascular diseases.

Main Methods:

• A biomimetic cardiac tissue chip (CTC) was engineered, encapsulating cardiac cells within 3-D fibers in a microfluidic chamber.
• The CTC system allows precise manipulation of hemodynamic parameters, including heart rate, pressures, volumes, and systolic/diastolic ratios.
• H9c2 cardiomyogenic cells were cultured under simulated pressure and volume overload conditions to assess model responsiveness.

Main Results:

• The CTC model successfully replicated pathological mechanical stresses, inducing morphological and gene expression changes in cardiac cells.
• Pressure overload simulation resulted in hypertrophic remodeling and fibrosis, mirroring cardiac hypertrophy.
• Volume overload simulation led to significant alterations in cellular aspect ratio, characterized by tissue thinning and elongation, mimicking dilated cardiomyopathy.

Conclusions:

• The cardiac tissue chip (CTC) provides a highly relevant in vitro model for cardiovascular disease research.
• The CTC accurately reproduces hemodynamic loading and unloading, facilitating the study of disease mechanisms and potential regenerative strategies.
• This model holds significant potential for advancing the understanding and treatment of cardiovascular conditions.