Impact of surface modification and loading time on orthodontic implant migration in the bone, and related micro-angiogenetic pattern and osteocytic gene expression.

骨整合种植体一直被认为是固定稳定的。然而，临床观察表明种植体可能会在骨中迁移，特别是在用作正畸锚定时。先前在大鼠脊柱模型中的临床前研究证实了这一观察结果，用于机械加工的、立即加载的种植体。种植体迁移在早期愈合阶段最为明显，并随着时间的推移而减少。同时伴有皮质和松质室的广泛骨质重塑和加载方向的增厚，这在组织学和显微CT中都可以看到。施加力的大小与早期愈合阶段的微血管生成参数显著相关，并倾向于与晚期较高的骨-种植体接触量相关。此时，各试验组加载方向均有较多的空骨陷窝。成骨细胞基因表达分析显示，合成代谢标志物Runx2在晚期有高表达趋势，分解代谢标志物硬化蛋白在愈合早期有高表达趋势。微细表面可促进骨结合，因此经常用于假体修复。牙种植体可以在植入后立即加载，也可以在骨整合完成后加载。目前尚不清楚种植体微地形和加载时间是否以及在多大程度上对种植体迁移有影响。此外，目前尚不清楚基因表达和负载诱导的骨细胞凋亡在多大程度上协调种植体的迁移。这些问题将在拟议的项目中进行研究。在n=80只雌性Wistar大鼠身上，两个定制的具有机械加工或微细加工表面的微型种植体将被插入到尾椎的背部，并由一个扁平的镍钛弹簧(1.0N)加载。在50%的动物中，负载将在淹没愈合后8周施加(延迟加载)，而在其余动物中，将在种植后直接施加(立即加载)。在两种加载方案中，50%的动物在1周后被处死，另外50%的动物在8周后被杀死。在体内，延迟愈合组在种植后0周和1周进行微型CT扫描。加载后，扫描将在0、1(所有动物)进行，对于加载8周后被处死的动物，也将在2、4和8周进行扫描。扫描将被用来量化种植体的迁移，检查相关的骨重建，并将骨重建与微观有限元分析相关联。处死后，对50%的大鼠进行非脱钙冰冻切片激光捕获显微解剖，进行局部基因表达分析。在另一半大鼠中，将评估微血管生成模式，然后通过免疫荧光和组织学的方法分析成骨细胞和破骨细胞的活性以及骨细胞的凋亡。

Osseointegrated implants have been considered to be stationary stable. However, clinical observations suggested that implants might migrate in bone, especially when serving as orthodontic anchorage.A previous preclinical study in the rat vertebral model corroborated this observation for machined, immediately loaded implants. Implant migration was most pronounced in the early healing phase and decreased over time. It was accompanied by extensive bone remodeling in the cortical and cancellous compartments and thickening in the direction of loading, which was visible histologically and in micro-CT. The amount of applied force was significantly associated with microangiogenic parameters in the early healing phase and tended to be associated with higher bone-to-implant contact in the late phase. At this time point, more empty lacunae were found in the loading direction in all test groups. Osteocytic gene expression analysis revealed a tendency for higher expression in the direction of loading of the anabolic marker Runx2 in the late and of the catabolic marker Sclerostin in early healing phase. Microrough surfaces promote osseointegration and are therefore frequently used for prosthetic implant restorations. Dental implants can be loaded either immediately after placement, or once the osseointegration has been achieved. It is still unclear if and to what extent implant microtopography and loading time have an impact on implant migration. Furthermore, it is unclear to what extent gene expression and loading-induced apoptosis of osteocytes orchestrate implant migration. These questions will be investigated in the proposed project.In n=80 female Wistar rats, two custom-made mini-implants with machined or microrough surfaces will be inserted into the dorsal part of a tail vertebra and loaded by a flat nickel-titanium spring (1.0N). In 50% of the animals, loading will be applied 8 weeks after submerged healing (delayed loading), whereas in the remaining animals it will be applied directly after implant placement (immediate loading). For both loading protocols, 50% of the animals will be killed after 1 week, and another 50% at 8 weeks of loading. In vivo micro-CT will be performed in the delayed healing group at 0 and 1 weeks following implant placement. Upon loading, scans will be performed at 0, 1 (all animals), and, in the animals killed after 8 weeks of loading, also at 2, 4, and 8 weeks. Scans will be utilized to quantify implant migration, to examine the associated bone remodeling, and to correlate bone remodeling with micro-finite elements analyses. After sacrifice, local gene expression analyses will be performed on 50% of all rats using laser capture microdissection on non-decalcified cryo-sections. In the other half of the rats, microangiogenic patterns will be assessed, followed by analyses of osteoblastic and osteoclastic activity and osteocytic apoptosis by means of immunofluorescence and histology.