Statin-loaded carbonated hydroxyapatite nanoemulsion controls matrix metalloproteinase-1 activity to enhance post-orthodontic stability in rats

Abstract

Background: The persistence of periodontal ligament (PDL) and alveolar bone remodeling following appliance removal is a key factor in orthodontic relapse, which is a significant barrier to treatment stability. In this study, a statin-loaded carbonated hydroxyapatite (CHA) nanoemulsion was evaluated as a local therapy to control relapse rate by modulating matrix metalloproteinase-1 (MMP-1) in rats. Methodology: A total of 48 rats (n=48) were allocated to control, simvastatin, CHA hydrogel, or CHA–simvastatin nanoemulsion groups. Treatments were delivered intrasulcularly during stabilization, and relapse was measured at days zero, one, seven, and 14 post-debonding. MMP-1 expression in the PDL was assessed using immunofluorescence at the same time points. Collected data were evaluated using analysis of variance. Results: Relapse occurred in all groups, with the highest relapse rate during early observation. At day one, the relapse rate was significantly reduced in treatment groups compared with the control, and the CHA–simvastatin group showed the lowest relapse rate (control 1048±20.20 vs. CHA–simvastatin 549.33±27.22 µmd-1; p=0.001). MMP-1 expression peaked at day one and was significantly lower in all treatment groups than control, with the greatest suppression in the CHA–simvastatin group (16.33±2.08 vs. 7.33±0.57 positive cells/field; p=0.001). By day 14, relapse rates and MMP-1 expression decreased across groups, with persisting advantages for the combined treatment. Conclusion: Local CHA–simvastatin nanoemulsion decreased early relapse and downregulated MMP-1 expression in rats, suggesting a promising adjunctive strategy to enhance post-orthodontic stability.