Dipyridamole Attenuates Experimental Peri-Implantitis By Regulating M1 Macrophage Polarization

To investigate the therapeutic effects of dipyridamole within an experimental rat model of peri-implantitis. The animal experiment was approved by ethics committee. Thirty 6-8-week-old male Sprague-Dawley rats received bilateral maxillary first molar extractions with immediate micro-implant placement. After 6 weeks, they were randomized into control (C), ligature and P.g co-induced peri-implantitis (PI), and PI with dipyridamole treatment (20 mg/kg/d, PI+D) groups (n=10/group). Five rats per group were euthanized at 4 and 8 weeks, respectively. Micro-CT quantified peri-implant bone loss. Hematoxylin-eosin staining evaluated peri-implant tissue destruction. Inflammatory cytokines (IL-1β, IL-6, TNF-α) were assessed via immunohistochemistry. Macrophage infiltration and M1 polarization were analyzed by immunofluorescence. One-way ANOVA with Bonferroni correction was used for statistical analysis. P < 0.05 was considered statistically significant. Micro-CT analysis conducted 8-week post-ligation demonstrated significantly greater peri-implant bone loss in the PI group compared with the C group (P < 0.05), whereas dipyridamole intervention in the PI+D group effectively attenuated bone loss (P < 0.05). Histopathological evaluations revealed substantially reduced degradation of both soft and hard tissues. In addition, the expression of pro-inflammatory mediators (IL-1β, IL-6, TNF-α) and M1 macrophage polarization markers were significantly downregulated in the PI+D group compare to the PI group (P < 0.05). Dipyridamole alleviated experimental peri-implantitis via suppression of macrophage M1 polarization, emerging as a hopeful pharmacological remedy for peri-implantitis.