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生物活性锌掺杂溶胶-凝胶涂层可调节蛋白质吸附模式和体外细胞反应。

Bioactive zinc-doped sol-gel coating modulates protein adsorption patterns and in vitro cell responses.

作者信息

Cerqueira A, Romero-Gavilán F, García-Arnáez I, Martinez-Ramos C, Ozturan S, Iloro I, Azkargorta M, Elortza F, Izquierdo R, Gurruchaga M, Goñi I, Suay J

机构信息

Department of Industrial Systems Engineering and Design, Universitat Jaume I, Av. Vicent Sos Baynat s/n, 12071 Castellón de la Plana, Spain.

Department of Industrial Systems Engineering and Design, Universitat Jaume I, Av. Vicent Sos Baynat s/n, 12071 Castellón de la Plana, Spain.

出版信息

Mater Sci Eng C Mater Biol Appl. 2021 Feb;121:111839. doi: 10.1016/j.msec.2020.111839. Epub 2020 Dec 30.

Abstract

Zinc is an essential element with an important role in stimulating the osteogenesis and mineralization and suppressing osteoclast differentiation. In this study, new bioactive ZnCl-doped sol-gel materials were designed to be applied as coatings onto titanium. The biomaterials were physicochemically characterized and the cellular responses evaluated in vitro using MC3T3-E1 osteoblasts and RAW264.7 macrophages. The effect of Zn on the adsorption of human serum proteins onto the material surface was evaluated through nLC-MS/MS. The incorporation of Zn did not affect the crosslinking of the sol-gel network. A controlled Zn release was obtained, reaching values below 10 ppm after 21 days. The materials were no cytotoxic and lead to increased gene expression of ALP, TGF-β, and RUNX2 in the osteoblasts. In macrophages, an increase of IL-1β, TGF-β, and IL-4 gene expression was accompanied by a reduced TNF-α liberation. Proteomic results showed changes in the adsorption patterns of proteins associated with immunological, coagulative, and regenerative functions, in a Zn dose-dependent manner. The variations in protein adsorption might lead to the downregulation of the NF-κB pathway, thus explain the observed biological effects of Zn incorporation into biomaterials. Overall, these coatings demonstrated their potential to promote bone tissue regeneration.

摘要

锌是一种必需元素,在刺激成骨作用和矿化以及抑制破骨细胞分化方面发挥着重要作用。在本研究中,设计了新型生物活性掺锌氯化物的溶胶-凝胶材料,用作钛表面的涂层。对生物材料进行了物理化学表征,并使用MC3T3-E1成骨细胞和RAW264.7巨噬细胞在体外评估了细胞反应。通过nLC-MS/MS评估了锌对人血清蛋白在材料表面吸附的影响。锌的掺入不影响溶胶-凝胶网络的交联。实现了锌的可控释放,21天后达到低于10 ppm的值。这些材料无细胞毒性,并导致成骨细胞中碱性磷酸酶(ALP)、转化生长因子-β(TGF-β)和 Runt 相关转录因子2(RUNX2)的基因表达增加。在巨噬细胞中,白细胞介素-1β(IL-1β)、TGF-β和IL-4基因表达的增加伴随着肿瘤坏死因子-α(TNF-α)释放的减少。蛋白质组学结果表明,与免疫、凝血和再生功能相关的蛋白质吸附模式以锌剂量依赖的方式发生变化。蛋白质吸附的变化可能导致核因子-κB(NF-κB)途径的下调,从而解释了观察到的锌掺入生物材料的生物学效应。总体而言,这些涂层显示出促进骨组织再生的潜力。

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