Enhancement of cell growth in tissue-engineering constructs under direct perfusion: Modeling and simulation

Area of Science:

• Biomedical Engineering
• Cellular Engineering
• Bioreactor Technology

Background:

• Perfusion bioreactors are crucial for improving mass transfer in cell-scaffold constructs for tissue engineering.
• Understanding nutrient flow, cell proliferation, and culture medium circulation is vital for optimizing engineered tissue growth.

Purpose of the Study:

• To develop and utilize a mathematical model simulating nutrient flow and cell growth within perfusion bioreactors.
• To investigate the impact of perfusion on cell distribution, proliferation, and shear stress within cell-scaffold constructs.

Main Methods:

• Developed a mathematical model incorporating modified Contois cell-growth kinetics and Michaelis-Menton kinetics for nutrient uptake.
• Applied Navier-Stokes and Brinkman equations to model fluid dynamics inside and outside the porous scaffold.
• Included time-dependent porosity and permeability changes due to cell growth to simulate perfusion effects.

Main Results:

• Direct perfusion led to greater cell penetration and more uniform spatial distribution within the scaffold.
• Cell proliferation increased with perfusion, approaching an asymptotic value with higher perfusion rates (Peclet number).
• Shear stresses increased with cell growth, but remained below the threshold for chondrocyte necrosis.

Conclusions:

• Mathematical modeling provides insights into optimizing perfusion bioreactor design for enhanced cell growth and distribution.
• Perfusion effectively balances nutrient delivery with manageable shear stress levels for engineered tissues.
• The model's predictions align with experimental findings, validating its utility in tissue engineering research.