Enhancing Osseointegration With LNP‐Delivered mRNA–Encoded BMP‐2: An Experimental In Vivo Study

ABSTRACT 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.