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一种通过递送双重治疗离子(锶、铜)来克服铜细胞毒性作用的新方法。

A new approach to overcome cytotoxic effects of Cu by delivering dual therapeutic ions (Sr, Cu).

作者信息

Anand Akrity, Sengupta Susanta, Galusek Dušan, Beltrán Ana M, Galusková Dagmar, Boccaccini Aldo R

机构信息

Centre for Functional and Surface Functionalized Glass, TnUAD, Trenčín 911 50, Slovakia; Institute of Biomaterials, University of Erlangen-Nuremberg, Erlangen 91058, Germany.

Centre for Functional and Surface Functionalized Glass, TnUAD, Trenčín 911 50, Slovakia; Institute of Biomaterials, University of Erlangen-Nuremberg, Erlangen 91058, Germany.

出版信息

J Trace Elem Med Biol. 2025 Feb;87:127565. doi: 10.1016/j.jtemb.2024.127565. Epub 2024 Nov 16.

Abstract

INTRODUCTION

The incorporation of trace elements such as strontium (Sr) and copper (Cu) in the composition of mesoporous bioactive glass (MBG) is widely known to enhance its biological functionality for bone tissue regeneration METHODS: Two MBG powders with the composition 80SiO-11CaO-5PO-xCuO/SrO, one doped with 4 mol.% of CuO, the second with 4 mol.% of SrO were blended in the weight ratios of Cu-MBG: Sr-MBG; 100:0, 70: 30, 50: 50, 30: 70 and 0:100 aiming at minimizing Cu to minimize the cytotoxicity of Cu while preserving its antimicrobial activity. The synergistic effects of Sr and Cu ions on bioactivity, cytotoxicity, and antimicrobial activity were studied.

RESULTS

Transmission electron microscopy (TEM) examination of Cu-MBG and Sr-MBG showed fringes related to the development of a mesoporous structure. The specific surface area values of the Cu-MBG and Sr-MBG powders were 287 and 349 m/g, respectively. A characteristic compact layer consisting of particles with platelet-like morphology commonly associated with HAp crystals was confirmed after 7 days soaking in simulated body fluid (SBF). Mouse preosteoblast cells (MC3T3-E1) exhibited higher cell viability when exposed to a 1 % w/v eluate from blended Cu-MBG powders compared to pure Cu-MBG. Notably, the Cu-MBG: Sr-MBG ratio of 30:70 exhibited cell viability of around 85 % at this concentration. A higher cell viability (above 100 %) towards MC3T3-E1 cells was observed for all powders when tested with the 0.1 % w/v eluate. With progressive increase in the amount of Cu-MBG in the blended system the bacterial inhibitory effects were more pronounced. The Cu ions released from Cu-MBG generate hydroxyl ions and increase the pH leading to disruption of the cellular membrane of microbes, resulting in enhanced antimicrobial activity.

CONCLUSION

This newly developed blended system composed of Cu and Sr doped MBGs is expected to be more effective as bioactive filler in comparison to single ion doped MBGs for bone tissue engineering applications.

摘要

引言

众所周知,在介孔生物活性玻璃(MBG)的组成中掺入锶(Sr)和铜(Cu)等微量元素可增强其对骨组织再生的生物学功能。方法:两种组成成分为80SiO-11CaO-5PO-xCuO/SrO的MBG粉末,一种掺杂4mol.%的CuO,另一种掺杂4mol.%的SrO,以Cu-MBG: Sr-MBG的重量比100:0、70:30、50:50、30:70和0:100进行混合,目的是尽量减少Cu以降低其细胞毒性,同时保留其抗菌活性。研究了Sr和Cu离子对生物活性、细胞毒性和抗菌活性的协同作用。

结果

对Cu-MBG和Sr-MBG的透射电子显微镜(TEM)检查显示出与介孔结构发展相关的条纹。Cu-MBG和Sr-MBG粉末的比表面积值分别为287和349m/g。在模拟体液(SBF)中浸泡7天后,确认形成了由通常与HAp晶体相关的片状形态颗粒组成的特征性致密层。与纯Cu-MBG相比,小鼠前成骨细胞(MC3T3-E1)暴露于混合Cu-MBG粉末的1%w/v洗脱液时表现出更高的细胞活力。值得注意的是,在此浓度下,Cu-MBG: Sr-MBG比例为30:70时细胞活力约为85%。当用0.1%w/v洗脱液测试时,所有粉末对MC3T3-E1细胞均观察到更高的细胞活力(超过100%)。随着混合体系中Cu-MBG含量的逐渐增加,细菌抑制作用更加明显。从Cu-MBG释放的Cu离子产生氢氧根离子并提高pH值,导致微生物细胞膜破坏,从而增强抗菌活性。

结论

与单离子掺杂的MBG相比,这种新开发的由Cu和Sr掺杂的MBG组成的混合体系有望作为生物活性填料在骨组织工程应用中更有效。

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