The potential of isotopically enriched magnesium to study bone implant degradation in vivo

摘要

Graphical abstract Display Omitted Abstract 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 26 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 ± 5 μm year ?1 , which corresponds with the degradation rate of pure Mg. Bone and tissue extraction was performed 4, 24, and 52 weeks after implantation. Bone cross sections were analyzed by laser ablation inductively coupled plasma mass spectrometry (ICP-MS) to determine the lateral 26 Mg distribution. The 26 Mg/ 24 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 200 ppm in bone tissues and 20 ppm in tissues up to two fold increased Mg levels with a contribution of pin-derived Mg of up to 75% (4 weeks) and 30% (24 weeks) 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 Δ 26 Mg/ 24 Mg values up to 16‰ were determined compared to control samples. Increased Δ 26 Mg/ 24 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 26 Mg/ 24 Mg ratios. This investigation showed that the organism is capable of handling excess Mg well and that bones fully recover after degradation. Statement of Significance 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 26 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.