Evaluating constrained and unconstrained mixture frameworks for predicting engineered heart tissue mechanics.

Area of Science:

• * Biomechanics
• * Computational Biology
• * Tissue Engineering

Background:

• * Engineered heart tissues (EHTs) are crucial for studying cardiac mechanics.
• * Current computational models often use a constrained mixture (CM) approach, assuming uniform deformation of tissue components.
• * This assumption may not fully capture the complex mechanobiology of EHTs.

Purpose of the Study:

• * To develop and evaluate an unconstrained mixture (UN-CM) modeling framework for EHTs.
• * To compare the UN-CM approach with the traditional CM framework.
• * To investigate the influence of independent component kinematics on EHT mechanical response.

Main Methods:

• * Extended an existing CM-based EHT modeling framework to an UN-CM framework.
• * Modeled kinematics of fibers and cells as independent variables constrained at cell-matrix adhesions.
• * Evaluated model predictions across idealized and tissue-specific scenarios.

Main Results:

• * Both CM and UN-CM models showed variations up to 40% in regional mechanical quantities (strain, strain rate, stress).
• * Strain rate exhibited the greatest variance between the two modeling approaches across all tests.
• * Localized mechanical differences were observed, highlighting the divergence of CM and UN-CM when considering fine-scale mechanics.

Conclusions:

• * The UN-CM framework offers flexibility in modeling EHT mechanobiology, particularly at local scales.
• * Differences between CM and UN-CM highlight the importance of considering independent component kinematics.
• * This work provides a new computational framework for studying diseases affecting cell-matrix adhesions in EHTs.