BIOPHYSICAL THEORY AND MODELING |
Cell Population Dynamics Modulate the Rates of Tissue Growth Processes
Gang Cheng 1, Belgacem Ben Youssef 2, Pauline Markenscoff 2 and Kyriacos Zygourakis 1*
1 Rice University
2 University of Houston
* To whom correspondence should be addressed. E-mail: kyzy{at}rice.edu.
Submitted on April 4, 2005
Revised on July 6, 2005
Accepted on 8 July 2005
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Abstract |
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The development and testing of a discrete model describing the dynamic process of tissue growth in 3D scaffolds is presented. The model considers populations of cells that execute persistent random walks on the computational grid, collide and proliferate until they reach confluence. To isolate the effect of population dynamics on tissue growth, the model assumes that nutrient and growth factor concentrations remain constant in space and time. Simulations start either by distributing the seed cells uniformly and randomly throughout the scaffold, or from an initial condition designed to simulate the migration and cell proliferation phase of wound healing. Simulations with uniform seeding show that cell migration enhances tissue growth by counterbalancing the adverse effects of contact inhibition. This beneficial effect, however, diminishes and disappears completely for large migration speeds. By contrast, simulations with the "wound" seeding mode show a continual enhancement of tissue regeneration rates with increasing cell migration speeds. We conclude that cell locomotory parameters and the spatial distribution of seed cells can have profound effects on the dynamics of the process and, consequently, on the pattern and rates of tissue growth. These results can guide the design of experiments for testing the effectiveness of biomimetic modifications for stimulating tissue growth.
Key Words:
cell migration, cell population dynamics, contact inhibition, discrete mathematical model, three-dimensional scaffold, tissue engineering