The influence of cyclic strain amplitude and timing of mechanical stimulation on secondary fracture healing.

Abstract

Introduction: Numerous systemic and local factors profoundly influence the repair process in bone. The purpose of this study was to investigate the effects of mechanical stimulation on the proliferation and differentiation of fracture repair tissues. Specifically, controlled cyclic interfragmentary strains were hypothesized to alter the mechanical and histomorphometric properties of repair tissues from the subcellular to the whole bone level. Materials and methods: Custom hinged external fixators were percutaneously applied to 110 adult male Sprague-Dawley rats using sterile surgical techniques. Controlled deformations were applied sinusoidally for 15 minutes at 0.5 Hz to a 1.0 millimeter femoral fracture gap every other day for the first and second, second and third, or third and fourth postoperative weeks. Following sacrifice at 28 days, all femora were harvested and scanned on a microcomputed tomography scanner for determination of volumetric fracture site mineralization. Pairs of femora from six animals per group were mechanically tested in external rotation for evaluation of bone integrity. The remaining femora were fixed in formalin, embedded in paraffin, and sectioned for histochemical and immunohistochemical studies of cellular activity and tissue distribution. Results: Whole-bone torsion tests could not detect differences among treatments in mechanical properties of the newly formed bone. Volumetric analysis of three-dimensional microcomputed tomography data revealed a higher bone volume fraction in animals treated early with a nonzero strain therapy. Histologic sections corroborated this result and showed an influence of strain history on type, amount, and distribution of repair tissues. Conclusions: This unique animal model was used to demonstrate correlations between tissue volume fraction and a known interfragmentary strain history. Results indicated that while the imposed cyclic mechanical environment changes the pattern of gap mineralization, this microstructural alteration has only a mild influence on whole bone integrity four weeks post-fracture. However, both magnitude and timing of cyclic strain therapy influenced histomorphometric properties of the fracture site such that fibrous tissue formed in areas of high strain magnitude while bone was observed in low strain regions.