A cell based modelling framework for skeletal tissue engineering applications

Abstract 

In this study, a cell based lattice free modelling framework is proposed to study cell aggregate behaviour in bone tissue engineering applications. The model encompasses cell-to-cell and cell–environment interactions such as adhesion, repulsion and drag forces. Oxygen, nutrients, waste products, growth factors and inhibitors are explicitly represented in the model influencing cellular behaviour. Furthermore, a model for cell metabolism is incorporated representing the basic enzymic reactions of glycolysis and the Krebs cycle. Various types of cell death such as necrosis, apoptosis and anoikis are implemented. Finally, an explicit model of the cell cycle controls the proliferation process, taking into account the presence or absence of various metabolites, sufficient space and mechanical stress. Several examples are presented demonstrating the potential of the modelling framework. The behaviour of a synchronised cell aggregate under ideal circumstances is simulated, clearly showing the different stages of the cell cycle and the resulting growth of the aggregate. Also the difference in aggregate development under ideal (normoxic) and hypoxic conditions is simulated, showing hypoxia induced necrosis mainly in the centre of the aggregate grown under hypoxic conditions. The next step in this research will be the application of this modelling framework to specific experimental set-ups for bone tissue engineering applications.

Keywords: Cell based model, Lattice-free, Skeletal tissue engineering