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

• Applicant: Professorin Dr. Kathrin Becker
• Subject Area: Dentistry, Oral Surgery
• Term: since 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 318755096

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.

• DFG Programme: Research Grants
• International Connection: Netherlands
• Co-Investigator: Dr. Beryl Schwarz-Herzke
• Cooperation Partner: Professor Dr. Bert van Rietbergen