Hybrid cellular automaton modeling of nutrient modulated cell growth in tissue engineering constructs.
Mathematic models help interpret experimental results and accelerate tissue engineering developments. We develop in this paper a hybrid cellular automata model that combines the differential nutrient transport equation to investigate the nutrient limited cell construct development for cartilage tissue engineering. Individual cell behaviors of migration, contact inhibition and cell collision, coupled with the cell proliferation regulated by oxygen concentration were carefully studied. Simplified two-dimensional simulations were performed. Using this model, we investigated the influence of cell migration speed on the overall cell growth within in vitro cell scaffolds. It was found that intense cell motility can enhance initial cell growth rates. However, since cell growth is also significantly modulated by the nutrient contents, intense cell motility with conventional uniform cell seeding method may lead to declined cell growth in the final time because concentrated cell population has been growing around the scaffold periphery to block the nutrient transport from outside culture media. Therefore, homogeneous cell seeding may not be a good way of gaining large and uniform cell densities for the final results. We then compared cell growth in scaffolds with various seeding modes, and proposed a seeding mode with cells initially residing in the middle area of the scaffold that may efficiently reduce the nutrient blockage and result in a better cell amount and uniform cell distribution for tissue engineering construct developments.
Chung
C A
CA
Institute of Biomedical Engineering, National Central University, Jhongli 32001, Taiwan, ROC. cachung@ncu.edu.tw
Lin
Tze-Hung
TH
Chen
Shih-Di
SD
Huang
Hsing-I
HI
D000465:Algorithms; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D003470:Culture Media; D004058:Diffusion / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008954:Models, Biological; D013997:Time Factors; D023822:Tissue Engineering; D054457:Tissue Scaffolds
D003470:Culture Media; D036341:Intercellular Signaling Peptides and Proteins