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用于临时心血管植入物的Mg-0.3Sr-0.3Ca的表面表征、体外和体内生物相容性

Surface characterization, in vitro and in vivo biocompatibility of Mg-0.3Sr-0.3Ca for temporary cardiovascular implant.

作者信息

Bornapour M, Mahjoubi H, Vali H, Shum-Tim D, Cerruti M, Pekguleryuz M

机构信息

Light Metals and Advanced Magnesium Materials, Mining and Materials Engineering, McGill University, Montreal, Qc, H3A 0C5, Canada; Biointerface Lab, Mining and Materials Engineering, McGill University, Montreal, Qc H3A 0C5, Canada.

Biointerface Lab, Mining and Materials Engineering, McGill University, Montreal, Qc H3A 0C5, Canada.

出版信息

Mater Sci Eng C Mater Biol Appl. 2016 Oct 1;67:72-84. doi: 10.1016/j.msec.2016.04.108. Epub 2016 May 3.

DOI:10.1016/j.msec.2016.04.108
PMID:27287101
Abstract

Magnesium-based alloys are attractive candidate materials for medical applications. Our earlier work showed that the ternary Mg-0.3Sr-0.3Ca alloy exhibits slower degradation rates than both binary Mg-Sr and Mg-Ca alloys. The ternary alloy immersed in simulated body fluid (SBF) forms a compact surface layer of corrosion products that we hypothesized to be a Sr-substituted hydroxyapatite (HA). The main objectives of the current work are to understand the bio-degradation mechanism of Mg-0.3Sr-0.3Ca, to identify the exact nature of its protective layer and to evaluate the in vitro and in vivo biocompatibility of the alloy for cardiovascular applications. To better simulate the physiological environment, the alloy was immersed in SBF which was daily refreshed. Raman spectroscopy and X-Ray photoelectron spectroscopy (XPS) confirmed the formation of a thin, Sr-substituted HA layer at the interface between the alloy and the corrosion products. In vitro biocompatibility evaluated via indirect cytotoxicity assays using HUVECs showed no toxicity effect and ions extracted from Mg-0.3Sr-0.3Ca in fact increased the viability of HUVECs after one week. In vivo tests were performed by implanting a tubular Mg-0.3Sr-0.3Ca stent along with a WE43 control stent into the right and left femoral artery of a dog. Post implantation and histological analyses showed no thrombosis in the artery with Mg-0.3Sr-0.3Ca stent after 5weeks of implantation while the artery implanted with WE43 stent was extensively occluded and thrombosed. Microscopic observation of the Mg-0.3Sr-0.3Ca implant-tissue interface confirmed the in situ formation of Sr-substituted HA on the surface during in vivo test. These results show that the interfacial layer protects the surface of the Mg-0.3Sr-0.3Ca alloy both in vitro and in vivo, and is the key factor in the bio-corrosion resistance of the alloy.

摘要

镁基合金是医学应用中颇具吸引力的候选材料。我们早期的研究表明,三元Mg-0.3Sr-0.3Ca合金的降解速率比二元Mg-Sr和Mg-Ca合金都要慢。浸入模拟体液(SBF)中的三元合金会形成一层致密的腐蚀产物表面层,我们推测其为锶取代的羟基磷灰石(HA)。当前工作的主要目标是了解Mg-0.3Sr-0.3Ca的生物降解机制,确定其保护层的确切性质,并评估该合金在心血管应用中的体外和体内生物相容性。为了更好地模拟生理环境,将该合金浸入每天更换的SBF中。拉曼光谱和X射线光电子能谱(XPS)证实,在合金与腐蚀产物的界面处形成了一层薄的锶取代HA层。通过使用人脐静脉内皮细胞(HUVECs)的间接细胞毒性试验评估的体外生物相容性显示没有毒性作用,事实上,从Mg-0.3Sr-0.3Ca中提取的离子在一周后提高了HUVECs的活力。体内试验是通过将管状Mg-0.3Sr-0.3Ca支架与WE43对照支架植入狗的左右股动脉进行的。植入后和组织学分析表明,植入Mg-0.3Sr-0.3Ca支架的动脉在植入5周后没有血栓形成,而植入WE43支架的动脉则广泛闭塞并形成血栓。对Mg-0.3Sr-0.3Ca植入物-组织界面的显微镜观察证实了在体内试验过程中表面原位形成了锶取代的HA。这些结果表明,界面层在体外和体内都保护了Mg-0.3Sr-0.3Ca合金的表面,并且是该合金生物耐腐蚀的关键因素。

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