Semaphorin Expression and Bone Resorption around Titanium and Zirconia Implants in Peri-Implantitis: an Experimental Study in Minipigs

Abstract

Semaphorins (Sema) are known to play an important role in bone remodeling by mediating the interactions between bone cells and immune cells. In this study, we investigated the differences in peri-implant bone resorption and the expression of Sema 3A and 4D around titanium (Ti) and zirconia (Zr) implants using a Göttingen minipig model of peri-implantitis. Bilateral mandibular first premolars were extracted in two minipigs, and after a 12-week healing period, three Ti and three Zr implants were placed. Peri-implant inflammation was experimentally induced by ligature placement, and peri-implant tissues were collected after an additional 12 weeks. The animals were divided into a control (Ctrl) group and a peri-implantitis (PI) group. Vertical and horizontal bone resorption was evaluated using cone-beam computed tomography with three-dimensional reconstruction, and Semaphorin expression in the surrounding alveolar bone was analyzed by quantitative real-time PCR (qRT-PCR). Significantly greater vertical bone resorption was observed around Ti implants (1.91 ± 0.32 mm in the Ctrl group and 4.55 ± 1.89 mm in the PI group) compared with Zr implants (1.32 ± 0.01 mm and 2.48 ± 0.36 mm, respectively). Similarly, horizontal bone resorption around Ti implants (1.10 ± 0.14 mm in the Ctrl group and 3.22 ± 0.45 mm in the PI group) was greater than that around Zr implants (0.76 ± 0.32 mm and 1.22 ± 0.15 mm, respectively). The bone resorption rate was also higher around Ti implants (16.4 ± 1.24% in the Ctrl group and 40.7 ± 8.66% in the PI group) than around Zr implants (9.0 ± 2.97% and 23.4 ± 3.08%, respectively). Sema 3A expression was higher in peri-implant bone around Zr implants (2.29 ± 0.26 ng/μL in the Ctrl group and 1.75 ± 0.09 ng/μL in the PI group) than around Ti implants (1.00 ± 0.12 ng/μL and 0.05 ± 0.08 ng/μL, respectively), whereas Sema 4D expression was more prominent around Ti implants (1.00 ± 0.12 ng/μL in the Ctrl group and 1.23 ± 0.06 ng/μL in the PI group) than around Zr implants (0.08 ± 0.19 ng/μL and 0.60 ± 0.18 ng/μL, respectively). In addition, Sema 4D expression exceeded that of Sema 3A regardless of inflammatory status. These findings indicate that differences in implant material may be associated with distinct Sema expression patterns, which could influence peri-implant bone remodeling, particularly through the involvement of Sema 4D in bone resorption around Ti implants.