Three-Dimensional Modeling of Avascular Tumor Growth in Both Static and Dynamic Culture Platforms

Abstract

Microfluidic cell culture platforms are ideal candidates for modeling the native tumor microenvironment because they can precisely reconstruct in vivo cellular behavior. Moreover, mathematical modeling of tumor growth can pave the way toward description and prediction of growth pattern as well as improving cancer treatment. In this study, a modified mathematical model based on concentration distribution is applied to tumor growth in both conventional static culture and dynamic microfluidic cell culture systems. Apoptosis and necrosis mechanisms are considered as the main inhibitory factors in the model, while tumor growth rate and nutrient consumption rate are modified in both quiescent and proliferative zones. We show that such modification can better predict the experimental results of tumor growth reported in the literature. Using numerical simulations, the effects of the concentrations of the nutrients as well as the initial tumor radius on the tumor growth are investigated and discussed. Furthermore, tumor growth is simulated by taking into account the dynamic perfusion into the proposed model. Subsequently, tumor growth kinetics in a three-dimensional (3D) microfluidic device containing a U-shaped barrier is numerically studied. For this case, the effect of the flow rate of culture medium on tumor growth is investigated as well. Finally, to evaluate the impact of the trap geometry on the tumor growth, a comparison is made between the tumor growth kinetics in two frequently used traps in microfluidic cell culture systems, i.e., the U-shaped barrier and microwell structures. The proposed model can provide insight into better predicting the growth and development of avascular tumor in both static and dynamic cell culture platforms.