Bone Formation Between 2.5 and 25% Interfragmentary Strain Induced by Immediate and Delayed Loading in a Bone Healing Model with a Monotonic Strain Gradient.

Abstract

This study investigated the formation of fracture repair tissue in response to 2.5-25% strain magnitudes under immediate and delayed loading in a large animal model with monotonically increasing interfragmentary strain. Experimental osteotomies were created in ten sheep and were instrumented with an active fixator that generated a gradient (2.5-25%) of interfragmentary strain across the osteotomy. Sheep were randomly assigned to an immediate-loading (from day 1 post-surgery) group or a delayed-loading (from day 22 post-surgery) group. Five weeks post-surgery, the tibiae were scanned using high-resolution computed tomography (CT). CT images were subsequently sliced at different strain levels. For each two-dimensional slice, we evaluated the area and density of fracture repair tissue within the osteotomy and the radial span of the periosteal tissue. Repeated-measures ANOVA tested the effects of strain magnitude and loading protocol on these parameters. The area and density of osteotomy repair tissue were highest at 2.5% of strain for both groups and significantly decreased when strain increased (p ≤ 0.015). In contrast, periosteal tissue span increased with strain (p < 0.001) and was significantly larger in the immediate-loading group (p < 0.01). Our study demonstrates the combined effect of strain (2.5-25%) and the timing of loading on bone healing. We observed two strain-related healing responses: up to ~ 7.5% strain, callus formed between the cortices, while higher strain shifted calcified repair tissue toward external callus. In this experimental model, strains below 25% provided a potent healing environment when stimulation was applied during the early healing stage.