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

骨结合种植体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，特别是当用作正畸锚定时。植入物移位在早期愈合阶段最为明显，并随时间推移而减少。伴随着皮质骨和松质骨间室的广泛骨重建，以及在载荷方向上的增厚，这在组织学和显微CT中可见。所施加的力的大小与早期愈合阶段的微血管生成参数显著相关，并且倾向于与晚期阶段较高的骨-种植体接触相关。在该时间点，在所有试验组中，在加载方向上发现更多空骨陷窝。骨细胞基因表达分析揭示了在晚期和早期愈合阶段的分解代谢标志物硬化蛋白的合成代谢标志物Runx 2的加载方向上的更高表达的趋势。微粗糙表面促进骨整合，因此经常用于假体植入物的修复。牙种植体可以在放置后立即加载，或者一旦实现骨整合就加载。目前尚不清楚种植体微形貌和加载时间是否以及在多大程度上对种植体迁移产生影响。此外，目前还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了种植体迁移。在n=80只雌性Wistar大鼠中，将两个定制的具有机加工或微粗糙表面的微型植入物插入尾椎的背部，并通过平坦的镍钛弹簧（1.0N）加载。在50%的动物中，将在浸没愈合后8周施加负载（延迟负载），而在其余动物中，将在植入体放置后直接施加负载（立即负载）。对于两种加载方案，50%的动物将在1周后被杀死，另外50%在加载8周时被杀死。在种植体植入后0周和1周，对延迟愈合组进行体内显微CT检查。加载后，将在0、1（所有动物）进行扫描，加载8周后处死的动物也将在2、4和8周进行扫描。将利用扫描来量化植入物移位，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，将使用激光捕获显微切割对50%的所有大鼠的非脱钙冷冻切片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分析成骨细胞和骨细胞活性以及骨细胞凋亡。

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.