Schlüsselwort: Mikroradiographie

Influence of combined mechanical and biological stimulation on defect healing – a microcomputed tomographic and biomechanical study of critical-sized bone defects in rats Generally it is known that the mechanical environment (stiffness of stabilization measures) is significant for the healing success of a fracture (Histings et al., 2010; Bartnikowski et al., 2017; Claes, 2017; Glatt et al., 2017). Under which biomechanical conditions a fast and efficient fracture healing would be achievable has been the subject of intensive research for some time (Claes, 2017). Additionally, several studies have shown the positive effect of BMP-2 for bone healing (Nauth et al., 2011; Wildemann et al., 2011). Extended knowledge of the impact of the dosing of growth factors and how much their interaction with mechanical stress can influence the efficiency of bone regeneration show possible future strategies for cases in which a bony bridging of the fracture gap has not yet been achieved. (Schmidt-Bleek & Willie et al., 2016). The aim of this work was to analyze the effects of varying fixation stiffness in combination with BMP-2 treatment in a critical sized defect (CSD) in a rat. 32 female Sprague Dawley rats, 12 weeks old, were randomized in four groups each of eight animals. Three experimental groups received a standardised critical 5 mm defect, 5μg rhBMP-2 was loaded on a absorbable collagen sponge and placed into the defect and stabilized with a flexible, semi-ride or rigide connecting element of the external fixator. The control group (1 mm osteotomy) mimicked an uncritical healing and was stabilized with the rigid fixator. All groups were analysed by in vivo micro-CT, perforrmed at day 10, 21 and 42 post-operation. At day 42 the rats were sacrificed and the osteomised left femora (including external fixator) were harvested. Additionally, the right intact femur of seven animals was harvested randomizedly. In the following, all samples were analysed by biomechanical in vitro testing for torsional stiffness and maximal torque value. The initial healing process of the stiffness groups was found with comparable tissue structure in the descriptive micro-CT. At day 10, in all stiffness groups moderate bone formation was detected along the periosteal defect site that was not sufficient for defect bridging. However, among the other stiffness groups, upon semi-rigid fixation, a tendency towards a higher level of mineralization was still found, which correlates with the largest statistically not significant TV-, BV- und TMC-values. Whereas the flexible group showed the lowest TV-value. On day 21 defects were bridged with bone tissue in all stiffness groups. As a result of the beginning maturing process, the micro-CT showed reabsorption processes. Delayed healing was found upon flexible fixation towards the other stiffness groups. Also a defect site with calcified and mineralized callus was found. On day 42, the flexible group showed significantly higher values for TV, BV, BV/TV and TMC, whereas the semi-rigid group showed the smallest of these values. This was seen by a defect site filled with mineralised callus upon flexible fixation, whereas the other stiffness groups had already shown reabsorption processes with rebuilding of the medullary cavitiy. Regarding TMD, the semi-rigid group showed the highest value, while flexible group showed the lowest value, but without any significance. The rigid group and the semi-rigid group showed a reduction of the total volume (TV) and also lower BV- and TMC-values as the flexible group - but also a lower TMD-value as the semi-rigid group. This leads to the presumption of a delayed maturing process. By using biomechanical in vitro tests, the semi-rigid group showed nearly equivalent results respective the torsional stiffness and the maximal torque at failure between the rigid and the flexible group. This study has shown that the BMP-2-stimulated defect healing is mechano-sensitive. Although marginal statistically significant differences in biomechanical and micro-CT results have been found, an accelerated healing process has been demonstraded upon semi-rigide and rigide group contrary to the flexible fixation – indicating a delayed boost of bone formation, whereas other stiffness groups had already shown reabsorption processes with rebuilding of the medullary cavitiy. This leads to the insight that the modulation of the mechanical environment of the critical defect has an impact on the healing process, despite the same BMP-2-treatment.