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

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology Pub Date : 2025-02-01 DOI:10.1016/j.jtemb.2024.127565

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

{"title":"A new approach to overcome cytotoxic effects of Cu by delivering dual therapeutic ions (Sr, Cu)","authors":"Akrity Anand , Susanta Sengupta , Dušan Galusek , Ana M. Beltrán , Dagmar Galusková , Aldo R. Boccaccini","doi":"10.1016/j.jtemb.2024.127565","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>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</div></div><div><h3>Methods</h3><div>Two MBG powders with the composition 80SiO<sub>2</sub>-11CaO-5P<sub>2</sub>O<sub>5</sub>-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.</div></div><div><h3>Results</h3><div>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<sup>2</sup>/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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"87 ","pages":"Article 127565"},"PeriodicalIF":3.6000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Trace Elements in Medicine and Biology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0946672X24001858","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

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 80SiO₂-11CaO-5P₂O₅-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 m²/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.

查看原文本刊更多论文

通过输送双重治疗离子（锶、铜）克服铜的细胞毒性效应的新方法。

简介：众所周知，在介孔生物活性玻璃（MBG）成分中掺入锶（Sr）和铜（Cu）等微量元素可增强其生物功能，促进骨组织再生。混合，重量比分别为 Cu-MBG：Sr-MBG：100:0、70:30、50:50、30:70 和 0:100，目的是将 Cu 的细胞毒性降至最低，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：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有关的流纹。铜-MBG 和锶-MBG 粉末的比表面积值分别为 287 和 349 m2/g。在模拟体液（SBF）中浸泡 7 天后，确认了由具有与 HAp 晶体常见的血小板状形态的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）暴露在混合 Cu-MBG 粉末的 1% w/v 洗脱液中时，细胞存活率更高。值得注意的是，铜-MBG：锶-MBG 的比例为 30:70，在此浓度下，细胞存活率约为 85%。在使用 0.1% w/v 洗脱液进行测试时，所有粉末对 MC3T3-E1 细胞都有较高的存活率（超过 100%）。随着混合体系中 Cu-MBG 含量的逐渐增加，抑菌效果更加明显。Cu-MBG 中释放的 Cu 离子会生成羟基离子，并提高 pH 值，从而破坏微生物的细胞膜，增强抗菌活性：这种新开发的由掺杂铜和锶的 MBG 组成的混合系统作为生物活性填料，与单离子掺杂的 MBG 相比，有望在骨组织工程应用中发挥更有效的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Trace Elements in Medicine and Biology 医学-内分泌学与代谢

CiteScore

6.60

自引率

2.90%

发文量

202

审稿时长

85 days

期刊介绍： The journal provides the reader with a thorough description of theoretical and applied aspects of trace elements in medicine and biology and is devoted to the advancement of scientific knowledge about trace elements and trace element species. Trace elements play essential roles in the maintenance of physiological processes. During the last decades there has been a great deal of scientific investigation about the function and binding of trace elements. The Journal of Trace Elements in Medicine and Biology focuses on the description and dissemination of scientific results concerning the role of trace elements with respect to their mode of action in health and disease and nutritional importance. Progress in the knowledge of the biological role of trace elements depends, however, on advances in trace elements chemistry. Thus the Journal of Trace Elements in Medicine and Biology will include only those papers that base their results on proven analytical methods. Also, we only publish those articles in which the quality assurance regarding the execution of experiments and achievement of results is guaranteed.