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潜在用于神经修复的镁合金的生物相容性和神经毒性。

Biocompatibility and neurotoxicity of magnesium alloys potentially used for neural repairs.

作者信息

Fei Jianjun, Wen Xiaoxiao, Lin Xiao, Wang Weihua, Ren Olga, Chen Xinjian, Tan Lili, Yang Ke, Yang Huilin, Yang Lei

机构信息

Orthopaedic Institute, Department of Orthopaedics, The First Affiliated Hospital, Soochow University, Suzhou, Jiangsu Province 215006, China; School of Electronics and Information Engineering, Soochow University, Suzhou, Jiangsu Province 215006, China.

Orthopaedic Institute, Department of Orthopaedics, The First Affiliated Hospital, Soochow University, Suzhou, Jiangsu Province 215006, China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2017 Sep 1;78:1155-1163. doi: 10.1016/j.msec.2017.04.106. Epub 2017 Apr 20.

DOI:10.1016/j.msec.2017.04.106
PMID:28575952
Abstract

Nerve injury, especially the large-size nerve damage, is a serious problem affecting millions of people. Entubulation of two ends of the injured nerve by using an implantable device, e.g., nerve guidance conduit (NGC), to guide the regeneration of nerve tissue is a promising approach for treating the large-size nerve defect. Magnesium (Mg) and its alloys are biodegradable, conductive, and own good mechanical properties. Mg ion, one of the main degradation products of Mg and its alloys, was reported to promote the proliferation of neural stem cells and their neurite production. Thus, Mg and its alloys are potential materials for fabricating the nerve repair implants, such as NGC or scaffold. However, the compatibility of Mg alloys to cells, especially neurons is not clear. In this work, NZ20 (Mg-2Nd-Zn), ZN20 (Mg-2Zn-Nd) and Mg-10Li magnesium alloys were selected for study, due to the improved mechanical properties of NZ20 and ZN20 alloys and bio-function of Li ions from Mg-10Li to nervous system, respectively. The degradation behavior and biocompatibility were studied by in vitro degradation test and cell adhesion assay, respectively. Specifically, the cytocompatibility to dorsal root ganglion (DRG) neurons, RF/6A choroid-retina endothelial cells, and osteoblasts in the cell culture media containing Mg alloy extracts were investigated. The results showed that Mg alloys degraded at different rates in cell culture media and artificial cerebrospinal fluid. The three alloy extracts showed negligible toxic effects on the endothelial cells and osteoblasts at short term (1 day), while NZ20 extract inhibited the proliferation of these two types of cells. The effect of Mg alloy extracts on cell proliferation was also concentration-dependent. For DRG neurons, ZN20 and Mg-10Li alloy extracts showed no neural toxicity compared with control group. The results of the present work show a potential and feasibility of Mg-10Li and ZN20 for nerve repair applications.

摘要

神经损伤,尤其是大尺寸神经损伤,是一个影响数百万人的严重问题。通过使用可植入装置(如神经导管(NGC))将受损神经的两端进行插管,以引导神经组织再生,是治疗大尺寸神经缺损的一种有前景的方法。镁(Mg)及其合金具有生物可降解性、导电性且机械性能良好。镁离子是镁及其合金的主要降解产物之一,据报道可促进神经干细胞的增殖及其神经突的产生。因此,镁及其合金是制造神经修复植入物(如NGC或支架)的潜在材料。然而,镁合金与细胞,尤其是神经元的相容性尚不清楚。在这项工作中,选择了NZ20(Mg-2Nd-Zn)、ZN20(Mg-2Zn-Nd)和Mg-10Li镁合金进行研究,分别是由于NZ20和ZN20合金机械性能的改善以及Mg-10Li中的锂离子对神经系统的生物功能。分别通过体外降解试验和细胞粘附试验研究了降解行为和生物相容性。具体而言,研究了在含有镁合金提取物的细胞培养基中对背根神经节(DRG)神经元、RF/6A脉络膜视网膜内皮细胞和成骨细胞的细胞相容性。结果表明,镁合金在细胞培养基和人工脑脊液中的降解速率不同。三种合金提取物在短期内(1天)对内皮细胞和成骨细胞显示出可忽略不计的毒性作用,而NZ20提取物抑制了这两种细胞的增殖。镁合金提取物对细胞增殖的影响也是浓度依赖性的。对于DRG神经元,与对照组相比,ZN20和Mg-10Li合金提取物未显示神经毒性。本工作的结果表明Mg-10Li和ZN20在神经修复应用中的潜力和可行性。

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