Mechano-regulation of mesenchymal stem cell differentiation and collagen organisation during skeletal tissue repair.

A number of mechano-regulation theories have been proposed that relate the differentiation pathway of mesenchymal stem cells (MSCs) to their local biomechanical environment. During spontaneous repair processes in skeletal tissues, the organisation of the extracellular matrix is a key determinant of its mechanical fitness. In this paper, we extend the mechano-regulation theory proposed by Prendergast et al. (J Biomech 30(6):539-548, 1997) to include the role of the mechanical environment on the collagen architecture in regenerating soft tissues. A large strain anisotropic poroelastic material model is used in a simulation of tissue differentiation in a fracture subject to cyclic bending (Cullinane et al. in J Orthop Res 20(3):579-586, 2002). The model predicts non-union with cartilage and fibrous tissue formation in the defect. Predicted collagen fibre angles, as determined by the principal decomposition of strain- and stress-type tensors, are similar to the architecture seen in native articular cartilage and neoarthroses induced by bending of mid-femoral defects in rats. Both stress and strain-based remodelling stimuli successfully predicted the general patterns of collagen fibre organisation observed in vivo. This provides further evidence that collagen organisation during tissue differentiation is determined by the mechanical environment. It is envisioned that such predictive models can play a key role in optimising MSC-based skeletal repair therapies where recapitulation of the normal tissue architecture is critical to successful repair.