Dynamic Control of Contractile Force in Engineered Heart Tissue.

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Stem Cell Technology

Background:

• Three-dimensional engineered heart tissues (EHTs) from human induced pluripotent stem cells (iPSCs) are vital for drug screening and heart disease research.
• Tissue contractility, a key phenotype, is influenced by preload and afterload.
• Current methods lack dynamic control over these mechanical parameters.

Purpose of the Study:

• To demonstrate a technique for controlling afterload in EHTs.
• To monitor and characterize the contractile force of EHTs under regulated conditions.
• To investigate the relationship between boundary stiffness and EHT contractility.

Main Methods:

• Developed a novel apparatus using piezoelectric actuators and microscopy for real-time feedback control.
• Implemented closed-loop control to dynamically regulate EHT boundary stiffness.
• Measured EHT force and length to assess contractile responses.

Main Results:

• EHT twitch force doubled upon switching from auxotonic to isometric boundary conditions.
• Characterized changes in EHT twitch force relative to effective boundary stiffness.
• Demonstrated dynamic regulation of EHT contractility through controlled boundary stiffness.

Conclusions:

• EHT contractility is dynamically regulatable via feedback control of effective boundary stiffness.
• This technique offers a new approach to probe tissue mechanics.
• Potential applications include mimicking in-vivo afterload changes and improving EHT maturation techniques.