MECHANOBIOLOGICAL MODELLING OF TISSUE DIFFERENTIATION INSIDE A MECHANICALLY-CONTROLLED BONE CHAMBER

Abstract

The influence of the mechanical environment on tissue differentiation has been widely investigated. However many questions remain about the actual process and the parameters that govern it. It has been proposed that tissue differentiation is driven by a biophysical stimulus which is a combination of fluid flow and octahedral shear strain. In order to further investigate the influence of the mechanical environment on tissue differentiation we have tested this hypothesis within a mechanically controlled bone chamber.

The bone chamber consists of a titanium cylinder with two bone ingrowth openings at one end which allow tissue to grow in from the subcortical cancellous bone. It is equipped with a piston protruding into the chamber for the application of a known pressure to the ingrowth tissue.

A 3D poroelastic finite element model of the inside of the bone chamber was developed. To model the dispersal of the various cell populations inside the tissue a lattice was created within each finite element, representing a space for both the cell and extracellular matrix. The differentiation process was ruled by fluid flow and shear strain. The change in tissue phenotype was implemented through a change in mechanical properties. Loading conditions corresponded to those applied during conducted experiments

High fluid flow and shear strain at the top and bottom of the chamber favoured tissue differentiation towards fibrous tissue. In the middle region, bone formed. A cartilage layer between the bone and the fibrous tissue was predicted, which is qualitatively in agreement with the experiments.

Although acceptable simulation/experiment comparison is achieved, in reality great variation is found in experiments, whereas our simulations are deterministic. It is clear that deterministic simulations can not capture the nature of tissue differentiation in this chamber. Nonetheless, tissue differentiation algorithms based on fluid/strain stimuli and using lattice models for biological activity are a promising tool in their ability to predict tissue differentiation inside a mechanically-controlled bone chamber.