Simulating the mechanical stimulation of cells on a porous hydrogel scaffold using an FSI model to predict cell differentiation

Abstract

3D-structured hydrogel scaffolds are frequently used in tissue engineering applications as they can provide a supportive and biocompatible environment for the growth and regeneration of new tissue. Hydrogel scaffolds seeded with human mesenchymal stem cells (MSCs) can be mechanically stimulated in bioreactors to promote the formation of cartilage or bone tissue. Although in vitro and in vivo experiments are necessary to understand the biological response of cells and tissues to mechanical stimulation, in silico methods are cost-effective and powerful approaches that can support these experimental investigations. In this study, we simulated the fluid-structure interaction (FSI) to predict cell differentiation on the entire surface of a 3D-structured hydrogel scaffold seeded with cells due to dynamic compressive load stimulation. The computational FSI model made it possible to simultaneously investigate the influence of both mechanical deformation and flow of the culture medium on the cells on the scaffold surface during stimulation. The transient one-way FSI model thus opens up significantly more possibilities for predicting cell differentiation in mechanically stimulated scaffolds than previous static microscale computational approaches used in mechanobiology. In a first parameter study, the impact of the amplitude of a sinusoidal compression ranging from 1% to 10% on the phenotype of cells seeded on a porous hydrogel scaffold was analyzed. The simulation results show that the number of cells differentiating into bone tissue gradually decreases with increasing compression amplitude, while differentiation into cartilage cells initially multiplied with increasing compression amplitude in the range of 2% up to 7% and then decreased. Fibrous cell differentiation was predicted from a compression of 5% and increased moderately up to a compression of 10%. At high compression amplitudes of 9% and 10%, negligible areas on the scaffold surface experienced high stimuli where no cell differentiation could occur. In summary, this study shows that simulation of the FSI system is a versatile approach in computational mechanobiology that can be used to study the effects of, for example, different scaffold designs and stimulation parameters on cell differentiation in mechanically stimulated 3D-structured scaffolds.