Heart Scar-In-A-Dish: Tissue Culture Platform to Study Myocardial Injury and Mechanics In Vitro

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Tissue Engineering

Background:

• Myocardial Infarction (MI) leads to ventricle damage and scar tissue formation.
• Current engineered heart tissues (EHTs) lack the complex mechanical environment of infarcted hearts.
• In vivo, infarcted ventricles exhibit heterogeneous mechanical forces: contraction in remote zones and stretching in infarct zones.

Purpose of the Study:

• To develop an in vitro three-dimensional tissue culture platform that replicates the heterogeneous mechanical environment of post-infarct myocardium.
• To investigate the mechanical changes and spatial variations in engineered heart tissues after induced injury.

Main Methods:

• Created three-dimensional engineered heart tissues (EHTs) using neonatal rat cardiomyocytes and fibroblasts.
• Induced localized cell death via cryo-wound injury in the central portion of beating EHTs.
• Analyzed tissue deformation (strains) and stiffness in wounded, border, and remote zones post-injury.

Main Results:

• The wounded zone experienced cyclic stretching (positive strains), while the remote zone continued to contract (negative strains).
• Tissue stiffness significantly increased in the wounded and border zones but remained unchanged in the remote zone.
• The platform successfully mimicked the spatially heterogeneous mechanical conditions found in post-MI hearts.

Conclusions:

• A novel in vitro platform was established to study myocardial mechanics after injury with spatial and temporal resolution.
• This model provides insights into the mechanical consequences of myocardial infarction.
• The platform can aid in developing and testing therapeutic strategies for heart repair, potentially reducing animal testing.