Numerous clinical conditions continue to drive the need to understand, both quantitatively and mechanistically, the relationship between physical forces and bone formation and adaptation. The global objective of this research was to investigate the influence of strain environment on patterns of tissue differentiation. To test hypotheses related to this overall objective, experimental animal models which take advantage of the large volume of bone formed during distraction osteogenesis (DO) were used to show how physical forces and strains influence bone regeneration at different stages of the repair process. The approach taken was: 1) to manipulate the mechanical environment within the mesenchymal gap tissue in vivo in a known fashion; 2) to predict the resulting changes in stresses and strains by computational and analytic means; and 3) to assess the effects of these changes on patterns of tissue differentiation. Correlations between strain environment and tissue response were then sought to gain insight into the relationship between these two entities. This abstract summarizes work done to accomplish these objectives in two different areas. First, both the time-dependent and large-deformation behavior of the mesenchymal distraction gap tissue were evaluated. Second, the strain environment was manipulated in three specific ways, and the effects of these changes on patterns of new bone formation and precursor tissue differentiation were assessed.