Organic tissues in rotating bioreactors: fluid-mechanical aspects, dynamic growth models, and morphological evolution

Area of Science:

• Biotechnology
• Computational Biology
• Tissue Engineering

Background:

• Rotary culture systems are crucial for 3D tissue engineering, providing a suitable environment for tissue assemblies.
• Tissue growth in these systems presents a moving boundary problem, influenced by fluid-dynamic shear stress.

Purpose of the Study:

• To develop and validate computational models for predicting organic construct growth in tissue engineering.
• To investigate the role of controlling forces, particularly fluid dynamics and shear stress, in tissue development.

Main Methods:

• A "volume-of-fraction" method was developed to model organic tissue growth, accounting for interface sensitivity to shear stress.
• Coupled differential equations were formulated for nutrient concentration and tissue mass evolution, incorporating surface conditions and momentum transfer.
• Sophisticated numerical simulations were employed to validate the models against experimental data.

Main Results:

• The developed models successfully predict characteristics of biological tissues grown in rotating-wall perfused vessel bioreactors.
• The interplay between tissue size and convective fields is critical in determining tissue shape evolution.
• Convective effects significantly impact growth rates, tissue size, morphology, and underlying growth mechanisms.

Conclusions:

• The computational models and numerical methods provide a validated approach for understanding tissue engineering phenomena.
• This approach offers novel capabilities for predicting experimental outcomes and elucidating cause-and-effect relationships in tissue growth.
• Understanding the influence of shear stress and convective forces is key to optimizing 3D tissue development.