Tissue growth in a rotating bioreactor. Part I: mechanical stability

Area of Science:

• Biomedical Engineering
• Mathematical Modeling
• Cell Biology

Background:

• Tissue constructs are essential in regenerative medicine.
• Rotating bioreactors are used for cell culture and tissue engineering.
• Understanding construct morphology is crucial for successful tissue development.

Purpose of the Study:

• To develop mathematical models for predicting tissue construct morphology in rotating bioreactors.
• To investigate the influence of mechanical forces and bioreactor parameters on cell self-assembly and construct shape.
• To analyze the interfacial stability of tissue constructs under varying conditions.

Main Methods:

• Mathematical modeling of a viscous fluid drop with an extensible membrane in an immiscible fluid.
• Analysis of thin-disk and slender-pipe bioreactor geometries.
• Examination of interfacial stability to oscillatory perturbations.
• Investigation of rotation rate, gravity, and material properties' effects.

Main Results:

• Below a critical rotation rate, cells self-assemble into smooth, cylindrical nodules.
• Above a critical rotation rate, an amorphous construct with an irregular boundary forms.
• The construct exhibits a denser interior of apoptotic cells and media, surrounded by a proliferating cell and collagen rim.
• Mathematical models predict construct morphology based on mechanical forces and system properties.

Conclusions:

• Bioreactor rotation rate is a key determinant of tissue construct morphology.
• Mechanical forces, driven by density differences and rotation, significantly influence cell self-assembly and construct shape.
• The developed models provide insights into optimizing bioreactor conditions for desired tissue construct development.