An interdisciplinary study based on animal experiments, cell culture s
tudies, and finite element models is presented. In a sheep model, the
influence of the osteotomy gap size and interfragmentary motion on the
healing success was investigated. Increasing gap sizes delayed the he
aling process, Increasing movement stimulated callus formation but not
tissue quality. Typical distributions of intramembranous bone, endoch
ondral ossification, and connective tissue in the fracture gap are qua
ntified. The comparison of the mechanical data determined by a finite
element model with the histologic images allowed the attribution of ce
rtain mechanical conditions to the type of tissue differentiation. Int
ramembranous bone formation was found for strains smaller than approxi
mately 5% and small hydrostatic pressure (<0.15 MPa). Strains less tha
n 15% and hydrostatic pressure more than 0.15 MPa stimulated endochond
ral ossification. Larger strains led to connective tissue. Cell cultur
e studies on the influence of strain on osteoblasts supported these fi
ndings. Proliferation and transforming growth factor beta production w
as increased for strains up to 5% but decreased for larger strains. Os
teoblasts under larger strains (>4%) turned away from the principal st
rain axis and avoided larger deformations. It is hypothesized that gap
size and the amount of strain and hydrostatic pressure along the calc
ified surface in the fracture gap are the fundamental mechanical facto
rs involved in bone healing.