Abstract

Local volume averaging approach was used for modeling and simulation of cell growth and proliferation, as well as glucose transfer within a cylindrical cartilage scaffold during cell cultivation. The scaffold matrix including the nutrient solution filling spaces among seeded cell colonies was treated as a porous medium. Applying differential mass balance of cells and glucose to a representative elementary volume of the scaffold, two diffusional mass transfer models were developed based on local volume averaged properties. The derived governing equations take into account time-dependent glucose diffusion, glucose consumption by cells, cell migration, apoptosis, and cell reproduction within the scaffold. Since the volumetric fraction of cells in the scaffold relies on cell growth, which strongly depends on glucose concentration in the scaffold, the governing equations were solved simultaneously using implicit finite difference method and Gauss-Seidel technique. Simulation results showed that cell volumetric fraction of the scaffold can reach about 45% after 50 days if a culture medium with a glucose concentration of 45 kgm−3 is used. Also, simulation results indicate that more uniform and higher average cell volume fraction of the scaffold can be obtained if biomanufacturing-based cell seeding is used across the scaffold rather than cell seeding on the scaffold surface.

Highlights

  • Nowadays tissue engineering has extensively attracted the attention of researchers to the development of biological substitutes for repairing or maintaining damaged tissues

  • Assessing the validity of Local Volume Averaging (LVA) approach revealed that LVA method can be used for modeling glucose transfer and cell proliferation in the cell-scaffold construct

  • Simulation results indicated that diffusional mass transfer resistance plays an important role in glucose concentration gradient occurring across the scaffold within 50 days (Figure 4)

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Summary

Introduction

Nowadays tissue engineering has extensively attracted the attention of researchers to the development of biological substitutes for repairing or maintaining damaged tissues. Three therapeutic strategies which can be adopted for treating a damaged tissue are (i) implantation of precultivated cells; (ii) implantation of preassembled tissues which have been regenerated in vitro; (iii) implantation of biocompatible and biodegradable scaffolds containing live cells for in situ regeneration. Live cells and growth factors are incorporated in a degradable scaffold which is implanted in the damaged tissue where growth of both tissue cells and cells in the scaffold promotes tissue healing [1]. The porosity of the scaffold should be sufficiently high to facilitate cell growth, cell migration, and nutrient transfer as well as transport of metabolic waste. While the scaffold should be sufficiently compliant not to damage surrounding tissues, it must be strong enough to support load forces and not to structurally collapse in the implanted site until the hard tissue transplant has been remodeled [2]

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