A mathematical model for cell differentiation, as an evolutionary and regulated process.

We introduce an approach which allows one to introduce the concept of cell plasticity into models for tissue regeneration. In contrast to most of the recent models for tissue regeneration, cell differentiation is considered a gradual process, which evolves in time and which is regulated by an arbitrary number of parameters. In the current approach, cell differentiation is modelled by means of a differentiation state variable. Cells are assumed to differentiate into an arbitrary number of cell types. The differentiation path is considered as reversible, unless differentiation has fully completed. Cell differentiation is incorporated into the partial differential equations (PDEs), which model the tissue regeneration process, by means of an advection term in the differentiation state space. This allows one to consider the differentiation path of cells, which is not possible if a reaction-like term is used for differentiation. The boundary conditions, which should be specified for the general PDEs, are derived from the flux of the fully non-differentiated cells and from the irreversibility of the fully completed differentiation process. An application of the proposed model for peri-implant osseointegration is considered. Numerical results are compared with experimental data. Potential lines of further development of the present approach are proposed.

Model for direct bone apposition on pre-existing surfaces, during peri-implant osseointegration.

In the present paper, a model for the early stages of peri-implant bone regeneration is developed. This model is able to capture some important characteristics of endosseous healing, which were not incorporated in the existing models. It is a well known fact, that during peri-implant osseointegration, bone forms only by apposition on the pre-existing rigid surface, which initially consists of the implant surface and the old bone surface. In order to track the movement of the front of the newly formed bone, a moving boundary problem is formulated. Another important feature of the current model, is that the cell differentiation is considered as a gradual process, evolving in time and being influenced by the presence of growth factors. Hence, the evolution of cell differentiation level is captured in the present approach. Numerical methods, used to solve the set of partial differential equations with hyperbolic terms, defined within the domain with the moving boundary, are described.