Jriyasetapong Kanoksiri, Lawtrakulngam Nopparada, Vivatbutsiri Philaiporn, Namano Sunporn, Wattanasirmkit Kamolporn, Angkhanawiriyarak Somphote, Suwanwela Jaijam
Department of Prosthodontics, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Sci Rep. 2025 May 22;15(1):17852. doi: 10.1038/s41598-025-02931-x.
This study evaluated the effectiveness of N1-methylpseudouridine-modified mRNA encoding bone morphogenetic protein-2 (BMP-2 mRNA-LNP) in promoting bone growth and improving titanium implant integration in rat femur bone defects. Sixteen Sprague-Dawley rats (32 femurs) were used, with titanium wires implanted in the femoral defects. The defects were divided into four groups (n = 8): 5 µg BMP-2 mRNA-LNP, 15 µg BMP-2 mRNA-LNP, recombinant BMP-2 (rhBMP-2), and Dulbecco's phosphate-buffered saline (dPBS). Following euthanasia at 3 and 6 weeks, Micro-Computed Tomography (micro-CT) was performed to assess bone volume, trabecular architecture, and bone-to-implant contact. Push-out mechanical testing determined the maximal loading force for implant dislodgment, while elemental analysis using Energy-Dispersive X-ray Spectroscopy (EDS) and Scanning Electron Microscopy (SEM) assessed mineralization on the titanium surfaces. The 15 µg BMP-2 mRNA-LNP group demonstrated significantly enhanced bone volume, trabecular thickness, and bone-to-implant contact compared to the control group (p < 0.05). Additionally, this group showed higher calcium and phosphorus content, indicating superior mineralization. Concomitantly, the mean maximal loading force (N) increased in the BMP-2 mRNA-LNP group, though this increase was not statistically significant. These results suggest that BMP-2 mRNA-LNP offers a promising approach to enhance peri-implant bone formation and bone regeneration. While the 15 µg group showed slightly greater bone formation, most experimental parameters showed no significant differences compared to the 5 µg group, suggesting the lower dose may offer a more cost-effective approach without compromising efficacy.
本研究评估了编码骨形态发生蛋白2的N1-甲基假尿苷修饰的信使核糖核酸（BMP-2信使核糖核酸-脂质纳米颗粒）在促进大鼠股骨骨缺损处骨生长及改善钛植入物整合方面的有效性。使用了16只Sprague-Dawley大鼠（32根股骨），在股骨缺损处植入钛丝。将缺损分为四组（n = 8）：5微克BMP-2信使核糖核酸-脂质纳米颗粒、15微克BMP-2信使核糖核酸-脂质纳米颗粒、重组骨形态发生蛋白2（rhBMP-2）和杜尔贝科磷酸盐缓冲盐水（dPBS）。在3周和6周实施安乐死后，进行微型计算机断层扫描（micro-CT）以评估骨体积、小梁结构和骨与植入物的接触情况。推出式力学测试确定植入物脱位的最大加载力，而使用能量色散X射线光谱仪（EDS）和扫描电子显微镜（SEM）进行的元素分析评估钛表面的矿化情况。与对照组相比，15微克BMP-2信使核糖核酸-脂质纳米颗粒组的骨体积、小梁厚度和骨与植入物的接触显著增强（p < 0.05）。此外，该组显示出更高的钙和磷含量，表明矿化情况更好。同时，BMP-2信使核糖核酸-脂质纳米颗粒组的平均最大加载力（牛顿）有所增加，尽管这种增加没有统计学意义。这些结果表明，BMP-2信使核糖核酸-脂质纳米颗粒为增强种植体周围骨形成和骨再生提供了一种有前景的方法。虽然15微克组的骨形成略多，但与5微克组相比，大多数实验参数没有显著差异，这表明较低剂量可能在不影响疗效的情况下提供更具成本效益的方法。
