Abstract
Background: Interfragmentary movements have benefits in the improvement of bone formation during distraction osteogenesis (DO). Although several clinical studies reported positive outcomes regarding the application of the cyclic distraction–compression (CDC) dynamization technique in cases with poor bone formation during DO, they are mostly anecdotal without a detailed description. The purpose of this study was to investigate the effectiveness and potential mechanism of different amplitudes and rates of the CDC technique on bone regeneration in a rat femur DO model. Methods: A total of 60 adult male Sprague-Dawley rats underwent right femoral mid-diaphysis transverse osteotomy and were randomly and evenly divided into Control (no manipulation), Group1 (CDC therapy), Group2 (CDC therapy with larger amplitude), and Group3 (CDC therapy with a slower rate) after distraction. The CDC technique was performed during the middle phase of the consolidation period according to different protocols. Animals were sacrificed after 4 and 6 weeks of consolidation. The process of bone formation was monitored by digital radiographs, and the regenerate bone was evaluated by micro-computed tomography (micro-CT), biomechanical test, and histological analysis. The serum contents of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were measured by enzyme-linked immunosorbent assay (ELISA). Results: Bone regeneration after the CDC technique was improved significantly during DO. The digital radiograph, micro-CT, histomorphological analysis, and biomechanical evaluation showed better effects regarding volume, continuity, and mechanical properties of the regenerate bone in Group2 and Group3 when compared to Group1. The angiogenic and osteogenic markers were more highly expressed in Group2 and Group3 than in Group1 according to the immunohistochemical analysis. As for ELISA, the serum contents of HIF-1α and VEGF were also increased after the CDC technique, especially in Group2 and Group3. Conclusion: The CDC dynamization technique has benefits on the improvement of bone formation during DO, and the mechanism may be due to tissue hypoxia activating the HIF pathway followed by the augmentation of osteogenic–angiogenic coupling. Better outcomes may be achieved by moderately increasing the amplitude and slowing down the rate of the CDC technique.
Highlights
Distraction osteogenesis (DO), firstly described by Ilizarov (1989a, 1989b, 1990) in the 1950s, has become a widely applied technique in orthopedic and reconstructive surgeries for limb lengthening, deformity correction, and bone defect caused by trauma, infection, or malignancy (Biz et al, 2021; Dahl and Morrison, 2021; El-Alfy et al, 2021)
After the cyclic distraction–compression (CDC) technique at week 3, bone regeneration was greater in Group1, Group2, and Group3
When the CDC was completed at week 4, a significant enhancement of regenerate consolidation was observed in Group2 and Group3
Summary
Distraction osteogenesis (DO), firstly described by Ilizarov (1989a, 1989b, 1990) in the 1950s, has become a widely applied technique in orthopedic and reconstructive surgeries for limb lengthening, deformity correction, and bone defect caused by trauma, infection, or malignancy (Biz et al, 2021; Dahl and Morrison, 2021; El-Alfy et al, 2021). Satisfactory outcomes have been achieved in most cases, the most important limitation of DO is the absence or delayed callus formation in the distraction gap, which can prolong the duration with a bulky frame needed for the regenerate bone to consolidate, resulting in unfavorable psychological impact and negative complications (Paley, 1990; Spiegl et al, 2013; Biz et al, 2021). Several clinical studies reported positive outcomes regarding the application of the cyclic distraction–compression (CDC) dynamization technique in cases with poor bone formation during DO, they are mostly anecdotal without a detailed description. The purpose of this study was to investigate the effectiveness and potential mechanism of different amplitudes and rates of the CDC technique on bone regeneration in a rat femur DO model
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