Modeling the Effect of Curvature on the Collective Behavior of Cells Growing New Tissue

The growth of several biological tissues is known to be controlled in part by local geometrical features, such as the curvature of the tissue interface. This control leads to changes in tissue shape that in turn can affect the tissue's evolution. Understanding the cellular basis of this control is highly significant for bioscaffold tissue engineering, the evolution of bone microarchitecture, wound healing, and tumor growth. Although previous models have proposed geometrical relationships between tissue growth and curvature, the role of cell density and cell vigor remains poorly understood. We propose a cell-based mathematical model of tissue growth to investigate the systematic influence of curvature on the collective crowding or spreading of tissue-synthesizing cells induced by changes in local tissue surface area during the motion of the interface. Depending on the strength of diffusive damping, the model exhibits complex growth patterns such as undulating motion, efficient smoothing of irregularities, and the generation of cusps. We compare this model with in vitro experiments of tissue deposition in bioscaffolds of different geometries. By including the depletion of active cells, the model is able to capture both smoothing of initial substrate geometry and tissue deposition slowdown as observed experimentally.