Differentiation can be thought of as a process by which cells and tissues undergo a change in phenotype toward a more specialized form or function. It is the contention of this thesis that tissue differentiation is in some way regulated by the mechanical environment of the cells within the tissue.

A theoretical model was developed which relates the dispersal, proliferation, and death of cells, and their subsequent differentiation, to their mechanical environment. In an attempt to confirm this mechano-regulation hypothesis, an algorithm based on the theoretical model was developed and used to simulate tissue differentiation during spontaneous osteochondral defect repair, where the mechanical environment within the defect was determined using finite element modelling. The influence of a number of physical factors, such as defect size and loading, were studied by altering these parameters in the finite element model. Furthermore, the influence of implanting a scaffold or engineered cartilage tissue on osteochondral defect repair was examined, where the mechanical properties of tissue engineered cartilage was determined experimentally.

The mechano-regulation model successfully predicted the main patterns of tissue differentiation observed during osteochondral defect repair. An increased amount of fibrous tissue formation, and reduced bone formation, was predicted as the size of the defect was increased. Only by implanting a scaffold or engineered tissue with mechanical properties approaching that or normal articular cartilage was the quality of repair predicted to significantly improve over spontaneous repair.

The ability of this model to simulate different aspects of tissue differentiation provides evidence to confirm our original hypothesis of mechano-regulated tissue differentiation. It is proposed as a tool to be used in the design o f orthopaedic implants and to evaluate future tissue engineering strategies.