Biomanufacturing versus Superficial Cell Seeding: Simulation of Chondrocyte Proliferation in a Cylindrical Cartilage Scaffold

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. 1. Introduction Nowadays tissue engineering has extensively attracted the attention of researchers to the development of biological substitutes for repairing or maintaining damaged tissues. Principally 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. In the third strategy, 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]. A cell-scaffold can be made of natural materials such as chitosan, collagen, and glycosaminoglycans or synthetic materials such as polyglycolic acid (PGA), polylactic acid (PLA), and polycaprolactone (PCL) by means of a biomanufacturing fabrication method. The scaffold features must satisfy some crucial conditions. The porosity of the scaffold should be sufficiently high to facilitate cell growth, cell migration, and nutrient transfer as well as transport of