Clinical, Biomechanical, Histopathological, and Imaging Characterization of an Ovine Large Femoral Bone Defect to Investigate New Treatment Strategies

Treatment of large bone defects are clinically challenging and preclinical sheep models are important to investigate new healing strategies. A representative study design includes positive and negative control groups. No surgical fixation has been published for treatment of an ovine large femoral defect, which allows bone healing in the positive control group, stabilizes an empty defect and investigates clinical, biomechanical, histopathological and imaging outcomes. A 26mm left mid-diaphyseal femoral defect was treated with the current clinical gold standard (Masquelet technique, positive control) (n=6) or was left empty (negative control, n=6). For the Masquelet technique, a cement block initially filled the defect, was removed four weeks later and replaced by autologous bone graft. A 8-hole broad 5.5mm locking plate (LCP) and a 7-hole narrow 4.5mm LCP were applied orthogonally. Diagnostic imaging was performed regularly until euthanasia, 20 weeks postoperatively. The explanted left femur was embedded in polymethylmethacrylate, mounted on a materials testing machine and interfragmentary movement was tracked with optical motion tracking. Femurs underwent non-destructive axial compression (100–160N) and torsional loading (0.5–1.5Nm) with two plates, one plate and no plate configuration. Eight contralateral femurs underwent the same loading regime. On µCT images three-dimensional volume of newly formed bone was determined. Defect bridging, defect closure and hyaline cartilage formation was evaluated on histological sections. Results All sheep reached the study end displaying uneventful clinical status. No sheep developed clinical complications and no signs of implant failure were detected on diagnostic imaging. Specimens in the Masquelet group had a significantly higher biomechanical stiffness (Table 1), higher 3D volume of new bone formation (16.3%, empty group: 7.4%), higher incidence of cortical bridging (83%, empty group: 20%) and increased new bone formation in the medullary area (≤75%, empty group: ≤50%) (Fig 1). Minimal hyaline cartilage was recorded in the empty group. Orthogonal plating using a broad 5.5mm and a narrow 4.5mm LCP is a reliable fixation to stabilize a 26mm femoral ovine bone defect. It results in stable fixation during a 5-month study period, even when no load sharing is expected. In the Masquelet group, newly formed bone had similar biomechanical properties to intact bone, confirming that the fixation allows a biomechanical environment for new bone formation. This model is considered suitable to investigate new treatment methods related to large bone defects. For any figures or tables, please contact the authors directly.