Abstract
The purpose of this study was to evaluate in vitro how the modulation of stiffness in a three-dimensional (3D) system independently influenced the behaviors of hepatocytes. Cells of a human hepatocyte cell line, C3A, which have been used in a clinically tested bioartificial liver support system, were conducted as cell models. Using a 3D system of "mechanically tunable" alginate hydrogels, matrix stiffness was modeled by corresponding to values in normal and fibrotic livers. Through observing the cellular morphology, viability, functional protein analysis, and gene expression, the effect of the 3D matrix stiffness on C3A cells was investigated. When cultured in stiff hydrogels (12 Kpa), C3A cells adopt a growth arrested and dedifferentiated phenotype, whereas in soft hydrogels (1 Kpa), they remain differentiated phenotype. The behavior of C3A cells can be modulated via independent tuning of mechanical stimuli in the 3D alginate hydrogels, which is different from that in the two-dimensional (2D) systems. The results indicate the importance of matrix stiffness choice for liver tissue engineering.
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