Tatu Rigwed, White Leon G, Yun Yeoheung, Hopkins Tracy, An Xiaoxian, Ashraf Ahmed, Little Kevin J, Hershcovitch Meir, Hom David B, Pixley Sarah
Department of Pharmacology & Systems Physiology, College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
PSN Labs (Plastics Services Network), Erie, PA 16510, USA.
Materials (Basel). 2023 Jan 30;16(3):1195. doi: 10.3390/ma16031195.
In vivo use of biodegradable magnesium (Mg) metal can be plagued by too rapid a degradation rate that removes metal support before physiological function is repaired. To advance the use of Mg biomedical implants, the degradation rate may need to be adjusted. We previously demonstrated that pure Mg filaments used in a nerve repair scaffold were compatible with regenerating peripheral nerve tissues, reduced inflammation, and improved axonal numbers across a short-but not long-gap in sciatic nerves in rats. To determine if the repair of longer gaps would be improved by a slower Mg degradation rate, we tested, in vitro and in vivo, the effects of Mg filament polishing followed by anodization using plasma electrolytic oxidation (PEO) with non-toxic electrolytes. Polishing removed oxidation products from the surface of as-received (unpolished) filaments, exposed more Mg on the surface, produced a smoother surface, slowed in vitro Mg degradation over four weeks after immersion in a physiological solution, and improved attachment of cultured epithelial cells. In vivo, treated Mg filaments were used to repair longer (15 mm) injury gaps in adult rat sciatic nerves after placement inside hollow poly (caprolactone) nerve conduits. The addition of single Mg or control titanium filaments was compared to empty conduits (negative control) and isografts (nerves from donor rats, positive control). After six weeks in vivo, live animal imaging with micro computed tomography (micro-CT) showed that Mg metal degradation rates were slowed by polishing vs. as-received Mg, but not by anodization, which introduced greater variability. After 14 weeks in vivo, functional return was seen only with isograft controls. However, within Mg filament groups, the amount of axonal growth across the injury site was improved with slower Mg degradation rates. Thus, anodization slowed degradation in vitro but not in vivo, and degradation rates do affect nerve regeneration.
可生物降解镁（Mg）金属在体内的应用可能会受到降解速度过快的困扰，即在生理功能修复之前金属支撑就已消失。为了推动镁生物医学植入物的应用，可能需要调整其降解速度。我们之前证明，用于神经修复支架的纯镁丝与再生的周围神经组织相容，可减轻炎症，并增加大鼠坐骨神经短间隙（而非长间隙）中的轴突数量。为了确定较慢的镁降解速度是否能改善更长间隙的修复效果，我们在体外和体内测试了镁丝抛光后再使用无毒电解质进行等离子体电解氧化（PEO）阳极氧化的效果。抛光去除了原始（未抛光）丝材表面的氧化产物，使更多的镁暴露在表面，产生了更光滑的表面，在生理溶液中浸泡四周后体外镁降解速度减缓，并改善了培养上皮细胞的附着。在体内，将经过处理的镁丝置于中空聚（己内酯）神经导管内，用于修复成年大鼠坐骨神经中更长（15毫米）的损伤间隙。将添加单根镁丝或对照钛丝的情况与空导管（阴性对照）和同基因移植（来自供体大鼠的神经，阳性对照）进行比较。在体内六周后，用微型计算机断层扫描（micro-CT）对活体动物成像显示，与原始镁相比，抛光使镁金属降解速度减慢，但阳极氧化并未使其减慢，阳极氧化反而引入了更大的变异性。在体内14周后，仅在同基因移植对照组中观察到功能恢复。然而，在镁丝组中，随着镁降解速度减慢，损伤部位的轴突生长量有所改善。因此，阳极氧化在体外减缓了降解，但在体内并未如此，而且降解速度确实会影响神经再生。
