Engineered 3D Cardiac Fibrotic Tissue to Study Fibrotic Remodeling

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Cell Biology

Background:

• Cardiac fibroblast activation into myofibroblasts drives cardiac remodeling and fibrosis.
• Spontaneous fibroblast activation in 2D cultures limits studying fibrotic processes.

Purpose of the Study:

• To develop a 3D hydrogel platform mimicking native heart tissue stiffness to maintain quiescent cardiac fibroblasts.
• To create a model for controlled activation of cardiac fibroblasts to study fibrotic remodeling.

Main Methods:

• Engineered a 3D hydrogel culture of cardiomyocytes and cardiac fibroblasts using gelatin methacryloyl.
• Mechanically tuned hydrogels to mimic native tissue stiffness.
• Stimulated constructs with transforming growth factor-β1 (TGF-β1) to induce fibrotic changes.

Main Results:

• Cardiac fibroblasts maintained quiescent phenotype in mechanically tuned 3D hydrogels.
• Engineered cardiac constructs exhibited physiological-like behavior with increased beating frequency upon beta-adrenergic agonist treatment.
• Controlled TGF-β1 addition successfully activated quiescent fibroblasts, leading to fibrotic protein marker expression and altered mechanical stiffness.

Conclusions:

• The developed 3D engineered cardiac tissue platform successfully maintains quiescent cardiac fibroblasts.
• This model enables controlled induction of cardiac fibrosis, offering a valuable tool for studying fibrotic remodeling and potential therapeutic interventions.