Draxler Johannes, Martinelli Elisabeth, Weinberg Annelie M, Zitek Andreas, Irrgeher Johanna, Meischel Martin, Stanzl-Tschegg Stefanie E, Mingler Bernhard, Prohaska Thomas
University of Natural Resources and Life Sciences Vienna, Department of Chemistry, Division of Analytical Chemistry - VIRIS Laboratory, Tulln, Austria.
Medical University of Graz, Department of Orthopaedics and Orthopaedic Surgery, Graz, Austria.
Acta Biomater. 2017 Mar 15;51:526-536. doi: 10.1016/j.actbio.2017.01.054. Epub 2017 Jan 20.
This pilot study highlights the substantial potential of using isotopically enriched (non-radioactive) metals to study the fate of biodegradable metal implants. It was possible to show that magnesium (Mg) release can be observed by combining isotopic mass spectrometry and isotopic pattern deconvolution for data reduction, even at low amounts of Mg released a from slowly degrading Mg enriched (>99%) Mg metal. Following implantation into rats, structural in vivo changes were monitored by μCT. Results showed that the applied Mg had an average degradation rate of 16±5μmyear, which corresponds with the degradation rate of pure Mg. Bone and tissue extraction was performed 4, 24, and 52weeks after implantation. Bone cross sections were analyzed by laser ablation inductively coupled plasma mass spectrometry (ICP-MS) to determine the lateral Mg distribution. The Mg/Mg ratios in digested tissue and excretion samples were analyzed by multi collector ICP-MS. Isotope pattern deconvolution in combination with ICP-MS enabled detection of Mg pin material in amounts as low as 200ppm in bone tissues and 20ppm in tissues up to two fold increased Mg levels with a contribution of pin-derived Mg of up to 75% (4weeks) and 30% (24weeks) were found adjacent to the implant. After complete degradation, no visual bone disturbance or residual pin-Mg could be detected in cortical bone. In organs, increased ΔMg/Mg values up to 16‰ were determined compared to control samples. Increased ΔMg/Mg values were detected in serum samples at a constant total Mg level. In contrast to urine, feces did not show a shift in the Mg/Mg ratios. This investigation showed that the organism is capable of handling excess Mg well and that bones fully recover after degradation.
Magnesium alloys as bone implants have faced increasing attention over the past years. In vivo degradation and metabolism studies of these implant materials have shown the promising application in orthopaedic trauma surgery. With advance in Mg research it has become increasingly important to monitor the fate of the implant material in the organism. For the first time, the indispensible potential of isotopically enriched materials is documented by applying Mg enriched Mg implants in an animal model. Therefore, the spatial distribution of pin-Mg in bone and the pin-Mg migration and excretion in the organism could be monitored to better understand metal degradation as well as Mg turn over and excretion.
这项初步研究突出了使用同位素富集(非放射性)金属来研究可生物降解金属植入物命运的巨大潜力。结果表明,通过结合同位素质谱法和同位素模式反褶积进行数据简化,即使从缓慢降解的富含镁(>99%)的镁金属中释放出少量的镁,也能够观察到镁(Mg)的释放。将其植入大鼠体内后,通过μCT监测体内结构变化。结果显示,所应用的镁的平均降解速率为16±5μm/年,这与纯镁的降解速率相符。在植入后4周、24周和52周进行骨和组织提取。通过激光烧蚀电感耦合等离子体质谱法(ICP-MS)分析骨横截面,以确定镁的横向分布。通过多接收ICP-MS分析消化组织和排泄样品中的Mg/Mg比值。同位素模式反褶积与ICP-MS相结合,能够检测到骨组织中低至200ppm的镁钉材料,在组织中低至20ppm,在植入物附近发现镁水平增加了两倍,其中高达75%(4周)和30%(24周)的镁来自镁钉。完全降解后,在皮质骨中未检测到明显的骨干扰或残留的钉状镁。在器官中,与对照样品相比,测定的ΔMg/Mg值增加高达16‰。在总镁水平恒定的血清样品中检测到ΔMg/Mg值增加。与尿液相反,粪便中的Mg/Mg比值没有变化。这项研究表明,生物体能够很好地处理过量的镁,并且骨骼在降解后能够完全恢复。
在过去几年中,镁合金作为骨植入物受到了越来越多的关注。这些植入材料的体内降解和代谢研究显示了其在骨科创伤手术中的应用前景。随着镁研究的进展,监测植入材料在生物体内的命运变得越来越重要。首次通过在动物模型中应用富含镁的镁植入物,证明了同位素富集材料的不可或缺的潜力。因此,可以监测骨中钉状镁的空间分布以及生物体中钉状镁的迁移和排泄,以更好地理解金属降解以及镁的周转和排泄。