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

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.