ESB Research Award 1996. Biophysical stimuli on cells during tissue differentiation at implant interfaces.

If musculoskeletal tissues are indeed efficient for their mechanical function, it is most reasonable to assume that this is achieved because the mechanical environment in the tissue influences cell differentiation and expression. Although mechanical stimuli can influence the transport of bioactive factors, cell deformation and cytoskeletal strain, the question of whether or not they have the potential to regulate tissue differentiation sequences (for example, during fracture healing or embryogenesis) has not been answered. To assess the feasibility of biophysical stimuli as mediators of tissue differentiation, we analysed interfacial tissue formation adjacent to a micromotion device implanted into the condyles of dogs. A biphasic finite element model was used and the mechanical environment in the tissue was characterised in terms of (i) forces opposing implant motion, (ii) relative velocity between constituents, (iii) fluid pressure, (iv) deformation of the tissue and (v) strain in the tissue. It was predicted that, as tissue differentiation progressed, subtle but systematic mechanical changes occur on cells in the interfacial tissue. Specifically, as the forces opposing motion increase, the implant changes from being controlled by the maximum-allowable displacement (motion-control) to being controlled by the maximum-available load (force-control). This causes a decrease in the velocity of the fluid phase relative to the solid phase and a drop in interstitial fluid pressure accompanied by a reduction in peri-prosthetic tissue strains. The variation of biophysical stimuli within the tissue can be plotted as 'mechano-regulatory pathway', which identifies the transition from motion-control to force-control as a branching event in the tissue differentiation sequence.