Three dimensional multi-scale modelling and analysis of cell damage in cell-encapsulated alginate constructs

Area of Science:

• Biomedical Engineering
• Tissue Engineering
• Computational Biology

Background:

• Scaffold-guided regenerative therapies require understanding mechanical cues for functional tissue formation.
• Predicting cellular responses to mechanical loads is crucial for maintaining cell phenotype in engineered tissues.

Purpose of the Study:

• To develop a 3D multi-scale numerical model to analyze cell stresses and deformations under macro-scale mechanical loads.
• To predict load-induced cell damage and cell viability within engineered tissue constructs.

Main Methods:

• Characterized macro-scale scaffold behavior and quantified 3D cell stresses and deformations at the micro-scale.
• Incorporated individual cell components and established a damage criterion based on critical load tolerance.
• Employed stochastic simulation to predict cell viability and validated with bio-printed cell-alginate constructs subjected to compression strain.

Main Results:

• Experimental cell viability decreased with increasing compression strain (1%, 5%, 10%).
• The developed model predicted cell viability trends consistent with experimental observations.
• Determined a mean critical compressive strain of 0.5% for the cell-alginate constructs.

Conclusions:

• The 3D multi-scale model accurately predicts cell viability and damage trends in response to mechanical loading.
• This computational methodology can guide the design of engineered tissues for regenerative medicine.
• Understanding mechanical forces is essential for controlling cellular responses and ensuring tissue construct success.