Extracellular macrostructure anisotropy improves cardiac tissue-like construct function and phenotypic cellular...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Cardiovascular Research

Background:

• Regenerative cardiac tissue holds therapeutic promise for myocardial repair, but poor electrical and contractile function hinders its clinical use.
• Scaffolds mimicking native myocardium structure can enhance physiological function in engineered cardiac constructs.
• Anisotropic extracellular architecture in engineered tissues improves contractility, signaling, and cellular organization compared to less ordered structures.

Purpose of the Study:

• To isolate and assess the impact of scaffold macroarchitecture on engineered cardiac tissue function.
• To understand how different scaffold designs influence cardiomyocyte behavior and tissue development.
• To provide insights for designing optimized cardiac tissues for regenerative medicine and disease modeling.

Main Methods:

• Fabrication of isotropic and aligned collagen scaffolds with conserved physio-mechanical properties.
• Seeding scaffolds with human embryonic stem cell-derived cardiomyocytes (hESC-CMs).
• Quantification of spatiotemporal tissue function via calcium signaling and contractile strain analysis, alongside examination of cellular organization and development.

Main Results:

• Aligned tissue constructs exhibited enhanced signaling synchronicity and directional contractility.
• Uniform cellular alignment was observed in tissues cultured on aligned scaffolds.
• Cells within aligned constructs displayed markers of increased phenotypic and genetic maturity.

Conclusions:

• Scaffold macroarchitecture significantly influences engineered cardiac tissue function, including electrical signaling and contractility.
• Aligned collagen scaffolds promote improved cellular organization and maturation of hESC-CMs.
• These findings are crucial for designing advanced cardiac tissues for regenerative therapies and in vitro models.