The purpose of this study was to investigate the effect of load-induced local mechanical strain on bone cell activity of peri-implant bone in mice. Titanium implants were placed in the maxillae of 13-week-old male C57BL/6J mice and subjected to intermittent 0.15 N, 0.3 N, or 0.6 N loads for 30 min/day for 6 days. The animals were sacrificed 2 days after the final loading. Unloaded mice were used as controls. An animal-specific three-dimensional finite element model was constructed based on morphological data retrieved from in vivo microfocus computed tomography for each mouse to calculate the mechanical strain distribution. Strain distribution images were overlaid on corresponding histological images of the same site in the same animal. The buccal cervical region of the peri-implant bone was predetermined as the region of interest (ROI). Each ROI was divided by four strain intensity levels: 0-20 με, 20-60 με, 60-100 με, and ≥100 με, and the bone histomorphometric parameters were analyzed by the total area of each strain range for all loaded samples. The distance between the calcified front and calcein labeling as a parameter representing the mineral apposition rate was significantly greater in the areas with strain intensity ≥100 με than in the area with strain intensity <100 με, suggesting that the bone formation activity of osteoblasts was locally enhanced by a higher mechanical strain. However, the shrunken osteocytes and the empty osteocyte lacunae were significantly lower in the highest strain area, suggesting that osteoclastogenesis was more retarded in higher strain areas than in lower strain areas. The histomorphometric parameters were not affected geometrically in the unloaded animals, suggesting that the load-induced mechanical strain caused differences in the histomorphometric parameters. Our findings support the hypothesis that bone cell activity related to bone resorption and formation is local strain-dependent on implant loading.

Department of Basic Oral Health Engineering Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University 1 5 45 Yushima Bunkyo ku Tokyo 113 8549 Japan

Institute of Solid Mechanics Mechatronics and Biomechanics Faculty of Mechanical Engineering Brno University of Technology Technická 2896 2 616 69 Brno Czech Republic

Removable Partial Prosthodontics Graduate School of Medical and Dental Sciences Tokyo Medical and Dental University 1 5 45 Yushima Bunkyo ku Tokyo 113 8549 Japan

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