Objective:To evaluate the effect of lipid nanoparticle (LNP)‐encapsulated N1‐methylpseudouridine‐modified mRNA encoding BMP‐2 (BMP‐2 mRNA‐LNP) on enhancing osseointegration and bone regeneration around titanium implants in rat femur defects.
Methods:A total of 48 rat femurs were examined in this study. BMP‐2 mRNA‐LNP (5 μg and 15 μg), recombinant human BMP‐2 protein (4 μg), or dPBS (control) were randomly injected in a single dose into distal rat femurs (n = 6). Titanium wires were implanted, and bone formation was evaluated at 3 and 6 weeks post treatment using micro‐computed tomography, histology, and immunohistochemistry analysis. Data were analyzed using the Kruskal‐Wallis test, followed by the Dunn‐Bonferroni test and the Wilcoxon signed‐rank test with 95% confidence intervals (CIs). p‐values < 0.05 were considered statistically significant.
Results:Micro‐computed tomography analysis of bone volume, bone volume fraction, trabecular number, trabecular thickness, and bone‐to‐implant contact at both time points indicated a trend toward greater bone formation in the mRNA groups compared to the other groups. Significant differences were observed between the 15 μg BMP‐2 mRNA‐LNP group and the dPBS group at 6 weeks (p < 0.05). The 15 μg BMP‐2 mRNA‐LNP group also exhibited the most intense positive bone sialoprotein and osteocalcin staining compared to the other groups at 3 weeks and 6 weeks, respectively. Interestingly, histomorphometry at 6 weeks revealed a significantly higher bone area around the implants in both 5 μg and 15 μg BMP‐2 mRNA‐LNP groups compared to the rhBMP‐2 and dPBS groups.
Conclusion:This preclinical study highlights the potential of BMP‐2 mRNA‐LNP for promoting bone regeneration around dental implants.