Anisotropic engineered heart tissue made from laser-cut decellularized myocardium

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Tissue Engineering

Background:

• Developing functional engineered heart tissues (EHTs) is crucial for studying cardiac mechanics and disease.
• Existing methods often lack the precision to control scaffold architecture and probe cellular responses to mechanical stimuli.

Purpose of the Study:

• To develop and validate a novel EHT system utilizing laser-cut decellularized myocardium scaffolds.
• To investigate the influence of scaffold architecture on cardiomyocyte behavior and biomechanical properties.
• To establish a platform for mechanotransduction studies and characterization of patient-derived cardiomyocytes.

Main Methods:

• Laser-cutting porcine myocardium into ribbon-like scaffolds, followed by decellularization.
• Seeding scaffolds with neonatal rat ventricular myocytes and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).
• Culturing and analyzing EHTs for synchronous beating, length-dependent activation, contractile anisotropy, and gene expression in response to mechanical stretch.

Main Results:

• Developed EHTs exhibited synchronous beating and length-dependent activation.
• Scaffold fiber orientation guided cellular anisotropy and influenced peak twitch stress.
• Stretch aligned with fiber direction increased brain natriuretic peptide expression, while off-axis stretch did not.
• hiPSC-EHTs demonstrated high peak stress and twitch kinetics comparable to adult human trabeculae.

Conclusions:

• Laser-cut decellularized myocardium scaffolds provide a viable platform for creating functional EHTs.
• This EHT system enables precise mechanotransduction experiments and characterization of patient-specific cardiac cells.
• The platform supports the development of advanced tools for cardiovascular research and drug discovery.