The Impact of Bone Regenerative Materials on Orthodontic Tooth Movement

Objectives: Bovine bone (BB) xenograft has been widely used in bone regeneration procedures. Clinical observations in human show impaired orthodontic-tooth-movement (OTM) into BB-regenerated-sites (BBRS), however, the biological mechanism of OTM in BBRS is not fully understood, mainly due-to lack of appropriate animal model. In this study, we aimed to (1) establish a novel in-vivo mouse model of OTM into BBRS (2) investigate the kinetics and biology of OTM into BBRS.
Methods: Osseous-defects were created by extraction of the upper-left-first-molar (M1) in C57BL/6-mice (n=44). Twenty-two experimental sockets were filled with bovine-bone, while the other 22 sockets remained unfilled (sponteous healing) and served as controls. 4 weeks post-regeneration, Ni-Ti closed-coil-springs were set-between M2 and the upper-incisors for 2 and 3 weeks (n=11/group/time-point) leading to mesial shift of M2 into BBRS. A fifth BB-group without-OTM served as control. Following sacrifice, Osseous-morphometrically-analysis and OTM-distance were evaluated by µCT-scanner. BB-characteristics and osteoclasts number were evaluated by H&E, TRAP-staining and SEM. Expression and location of bone-remodeling-cytokines RANKL and OPG were evaluated by immunofluorescence-staining.
Results: OTM-distance into BBRS were strikingly reduced following 2 and 3 weeks (p<0.05) compared to No-BB groups. Morphometrically and histological-analysis revealed an accumulation of BB-particles along the root's pressure-side of these groups (p<0.05), compared with 'BB without-OTM' group. Osteoclasts number was substantially increased in the 'OTM into BBRS' groups compared to the controls (p<0.05). SEM revealed osteoclasts located on the BB-particles although no significant BB resorption was observed. Immunofluorescence-staining showed targeting of RANKL-cytokine, but not OPG, on the BB-particles located in the pressure-zone following OTM.
Conclusions: Despite 'proper' osteo-immune reaction, the osteoclasts failed to resorb the BB-particles, which accumulate along the root's pressure-side leading to “mechanical-obstruction” and impairment of OTM into BBRS. Our novel mouse model will allow future molecular and genetic-investigations for better understanding the dynamics of OTM into regenerated-sites and may contribute to find a novel therapeutic-means to clinically control it.