Strain-Dependent Effects of Controlled Micromotion on Fracture Healing: Rethinking the Strain Threshold.

Abstract

The strain required to optimize controlled micromotion in indirect (callus-mediated) fracture healing remains uncertain. Although the classic 2% to 10% strain range proposed by Perren is widely cited, several animal and clinical studies have reported healing at higher strain levels. This study evaluated the strain-healing relationship in a controlled micromotion model. We hypothesized that the strain threshold that supports healing exceeds 10%. A standardized 2-mm transverse osteotomy was created in Sprague-Dawley rats and stabilized with an external fixator capable of delivering precise micromotion. Five strain levels (0%, 10%, 20%, 30%, 40%) were applied once daily at 0.5 Hz for 30 minutes beginning 2 weeks after surgery and continued for 2 weeks. Healing was assessed by radiographs, micro-computed tomography, mechanical testing, histology, and immunohistochemistry. A strain level of 20% was associated with the most favorable overall healing profile across radiographic, structural, and mechanical assessments, with no cases of nonunion. Lower strains demonstrated limited callus formation, while higher strains produced abundant early cartilage but delayed conversion to bone and reduced mineralization. Moderate strain was accompanied by balanced expression of IL-6, IL-1β, and RANKL/OPG, whereas excessive strain showed patterns consistent with impaired remodeling. Under stable fixation and before the fracture gap transitions to stiffer cartilaginous tissue, the functional upper limit of beneficial strain appears to exceed the traditional 10% threshold. Approximately 20% of compressive strain, applied between day 14 and 21 postosteotomy, provided the most balanced combination of early repair and subsequent remodeling in this model. These findings suggest that controlled micromotion with 20% interfragmentary strain may be most relevant to fractures managed under relative stability and healing through callus formation. However, faster callus-mediated healing is not inherently clinically advantageous, and its value depends on fracture type, anatomical site, and fixation strategy.