Analysis of cell growth and diffusion in a scaffold for cartilage tissue engineering

Developments in tissue engineering over the past decade have offered promising future for the repair and reconstruction of damaged tissues. To regenerate three dimensional and weight‐bearing implants, advances in biomaterials and manufacturing technologies prompted cell cultivations with natural or artificial scaffolds, in which cells are allowed to proliferate, migrate, and differentiate in vitro. In this article, we develop a mathematical model for cell growth in a porous scaffold. By treating the cell‐scaffold construct as a porous medium, a continuum model is set up based on basic principles of mass conservation. In addition to cell growth kinetics, we incorporate cell diffusion in the model to describe the effects of cell random walks. Computational results are compared to experimental data found in the literature. With this model, we are able to investigate cell motility, heterogeneous cell distributions, and non‐uniform seeding for tissue engineering applications. Results show that random walks tend to enhance uniform cell spreads in space, which in turn increases the probabilities for cells to acquire nutrients; therefore random walks are likely to be a positive contribution to the overall cell growth on scaffolds. © 2006 Wiley Periodicals, Inc.

[1]  A. Curtis,et al.  Articular chondrocyte passage number: Influence on adhesion, migration, cytoskeletal organisation and phenotype in response to nano‐ and micro‐metric topography , 2005, Cell biology international.

[2]  Stephen Whitaker,et al.  Diffusion and reaction in cellular media , 1986 .

[3]  R T Tranquillo,et al.  The fibroblast-populated collagen microsphere assay of cell traction force--Part 2: Measurement of the cell traction parameter. , 1995, Journal of biomechanical engineering.

[4]  L. Griffith,et al.  Tissue Engineering--Current Challenges and Expanding Opportunities , 2002, Science.

[5]  H. Berg Random Walks in Biology , 2018 .

[6]  G. Vunjak‐Novakovic,et al.  Composition of cell‐polymer cartilage implants , 1994, Biotechnology and bioengineering.

[7]  L. Bonassar,et al.  Comparison of Chondrogensis in Static and Perfused Bioreactor Culture , 2000, Biotechnology progress.

[8]  D. E. Contois Kinetics of bacterial growth: relationship between population density and specific growth rate of continuous cultures. , 1959, Journal of general microbiology.

[9]  G. Vunjak‐Novakovic,et al.  Enhanced cartilage tissue engineering by sequential exposure of chondrocytes to FGF‐2 during 2D expansion and BMP‐2 during 3D cultivation , 2001, Journal of cellular biochemistry.

[10]  Hsueh-Chia Chang,et al.  Effective diffusion and conduction in two‐phase media: A unified approach , 1983 .

[11]  R Langer,et al.  Kinetics of chondrocyte growth in cell‐polymer implants , 1994, Biotechnology and bioengineering.

[12]  Bojana Obradovic,et al.  Glycosaminoglycan deposition in engineered cartilage: Experiments and mathematical model , 2000 .

[13]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[14]  D. Lauffenburger,et al.  Motile chondrocytes from newborn calf: migration properties and synthesis of collagen II. , 2003, Osteoarthritis and cartilage.

[15]  G. Vunjak‐Novakovic,et al.  Gas exchange is essential for bioreactor cultivation of tissue engineered cartilage. , 1999, Biotechnology and bioengineering.

[16]  C. Galbán,et al.  Analysis of cell growth kinetics and substrate diffusion in a polymer scaffold. , 1999, Biotechnology and bioengineering.

[17]  Jos Malda,et al.  Heterogeneous proliferation within engineered cartilaginous tissue: the role of oxygen tension. , 2005, Biotechnology and bioengineering.

[18]  C. Galbán,et al.  Effects of spatial variation of cells and nutrient and product concentrations coupled with product inhibition on cell growth in a polymer scaffold. , 1999, Biotechnology and bioengineering.

[19]  C. Hidaka,et al.  Maturational differences in superficial and deep zone articular chondrocytes , 2005, Cell and Tissue Research.

[20]  C. V. van Blitterswijk,et al.  The effect of PEGT/PBT scaffold architecture on the composition of tissue engineered cartilage. , 2005, Biomaterials.

[21]  N A Peppas,et al.  New challenges in biomaterials. , 1994, Science.

[22]  A. Hall,et al.  Regulatory volume decrease (RVD) by isolated and in situ bovine articular chondrocytes , 2001, Journal of cellular physiology.

[23]  Michel Quintard,et al.  Calculation of effective diffusivities for biofilms and tissues , 2002, Biotechnology and bioengineering.

[24]  S. Abramson,et al.  Effects of nitric oxide on chondrocyte migration, adhesion, and cytoskeletal assembly. , 1996, Arthritis and rheumatism.

[25]  T J Pedley,et al.  The development of concentration gradients in a suspension of chemotactic bacteria. , 1995, Bulletin of mathematical biology.