Effect of Magnetic Nanosystem on Regulation of Macrophage Polarization to Treat Diabetic-Associated Apical Periodontitis

Objectives: The incidence of apical periodontitis was approximately three times higher in diabetic patients than in non-diabetic patients. The hyperglycemic microenvironment mediates the over-polarization of M1 macrophages and inhibits M2 polarization, resulting in osteogenic and osteogenic imbalances, which are among the most prominent factors in the diabetic periapical inflammation. Targeting the periapical region, reversing the hyperglycemic microenvironment, and temporally modulating macrophage polarization are current therapeutic directions. In the study, novel compounds of magnetic nanoparticles, dendritic macromolecules, and metformin were designed(PMM). The complex can target the periapical region, reverse the hyperglycemic microenvironment, modulate the polarization of macrophages in time series, and promote periapical bone repair. It is expected to be used in the treatment of periapical inflammation in diabetics.
Methods: The novel compound was synthesized first. Here, we explored the physical and chemical properties of the novel compound using transmission electron microscope, magnetic inspection and so on. Macrophages and BMSCs were used to elucidate the anti-inflammatory effects and potential mechanisms. A diabetic rat model of apical periodontitis was applied to further explore the anti-bone resorption effects.
Results: PMM showed excellent biocompatibility. We also found that PMM first utilizes magnetic targeting to direct the complex to the periapical region. It modulates the high-sugar microenvironment in the periapical area, inhibits M1 polarization, and enhances the phagocytic function of macrophages. Under the acidic conditions of the diabetic periapical environment, the peptide chains of PAMAM and MNP break, releasing a large amount of metformin loaded in the mesopores. This activates the AMPK/PGC-1α/PPAR-γ pathway, regulating M2 polarization, and ultimately promoting bone regeneration in diabetic periapical periodontitis.
Conclusions: This study is the first to report the sequential benefits of PMM and the first to demonstrate its potential in clinical applications for the inhibition of diabetes-associated apical periodontitis.