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首页> 外文期刊>Journal of biomedical materials research. Part B, Applied biomaterials. >In vitro evaluation of orthopedic composite cytotoxicity: assessing the potential for postsurgical production of hydroxyl radicals.
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In vitro evaluation of orthopedic composite cytotoxicity: assessing the potential for postsurgical production of hydroxyl radicals.

机译:骨科复合材料细胞毒性的体外评估:评估术后产生羟基自由基的潜力。

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摘要

Hydroxyl radical (*OH)-induced inflammation is a primary mode for in vivo cytotoxicity. A legitimate concern is whether particulate wear debris from orthopedic composites can stimulate inflammation via ferrous ion (Fe2+)-mediated production of *OH. The purpose of this research was to utilize electron paramagnetic resonance (EPR) spin trapping in investigating and comparing the potential for postsurgical cytotoxicity induced specifically by *OH in the presence of two composites: Simplex P and the novel, hybrid, CORTOSS. Cytotoxicity is evaluated based on the composites competitively chelating catalytic Fe2+ or readily reducing ferric ions (Fe3+), in facilitating the Fenton reaction (FR). *OH that are produced were then validated by a radical scavenger to confirm a genuine radical signal and mechanism. Spin adduct peak areas decreased in the presence of CORTOSS as opposed to increasing in the presence of Simplex P, evaluated against their respective controls. A plausible theory elucidating this finding is that CORTOSS may sequester the Fe form, by virtue of its monomers. Principally, direct comparison of composites indicated that Simplex P had greater tendency to produce *OH, yielding 25.6 and 48.7% greater spin adduct peak areas when chelated and non-chelated Fe2+ are used, respectively. Moreover, the rate of FR accelerated when chelated Fe2+ was used, leading to the formation of a ternary complex with the composites. This was more prominent in Simplex P, as coordination of chelated Fe2+ occurs on its surface via an electrostatic attraction to allow a seventh coordination site for ligand exchange in the ternary complex, stabilized by Ba2+. Conversely, the silica found in CORTOSS possesses radical quenching abilities that deactivate generated *OH in impeding the efficiency of FR. Neither composite demonstrated a capacity to readily reduce Fe3+ to the relevant Fe2+, as validated by a non-radical pathway. Instead, the artificial spin adduct signal attained when employing chelated Fe3+ was due to the nucleophilic addition of water onto DMPO. Simplex P may also serve as a template for surface catalysis of the nucleophilic addition of water onto DMPO involving chelated Fe3+. CORTOSS is thought not to induce cytotoxicity, whereas the propensity of Simplex P in promoting Fenton chemistry is a serious issue that must be addressed.
机译:羟自由基(* OH)诱导的炎症是体内细胞毒性的主要模式。一个合理的问题是,骨科复合材料的颗粒磨损碎片是否可以通过亚铁离子(Fe2 +)介导的* OH产生刺激炎症。这项研究的目的是利用电子顺磁共振(EPR)自旋捕获技术来研究和比较* OH在两种复合物(单纯形P和新型杂化CORTOSS)的存在下由* OH特异性诱导的术后细胞毒性的潜力。基于促进Fenton反应(FR)的竞争性螯合催化性Fe2 +或易于还原的铁离子(Fe3 +)的复合材料,评估细胞毒性。然后由自由基清除剂验证产生的* OH,以确认真正的自由基信号和机理。旋转加合物峰面积在CORTOSS存在下有所降低,而在Simplex P存在下却有所增加(对照各自的对照进行评估)。阐明这一发现的合理理论是,CORTOSS可以凭借其单体螯合Fe形式。原则上,直接比较复合材料表明,当使用螯合的和非螯合的Fe2 +时,Simplex P更有可能产生* OH,分别产生25.6和48.7%的自旋加合物峰面积。此外,当使用螯合的Fe2 +时,FR的速率加快,导致与复合物形成三元复合物。这在单工P中更为突出,因为螯合的Fe2 +通过静电吸引作用在其表面发生配位,从而允许第七配位位点在三价配合物中被配体交换,并由Ba2 +稳定。相反,在CORTOSS中发现的二氧化硅具有自由基猝灭能力,可以使生成的* OH失活,从而阻碍FR的效率。两种复合物均未显示出将Fe3 +轻松还原为相关Fe2 +的能力,这已通过非自由基途径进行了验证。相反,当使用螯合的Fe3 +时获得的人工自旋加合物信号是由于水向DMPO的亲核加成。 Simplex P也可以用作模板,用于水的亲核加成反应对涉及螯合Fe3 +的DMPO进行表面催化。人们认为CORTOSS不会诱导细胞毒性,而单纯形P在促进Fenton化学上的倾向是必须解决的严重问题。

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