Titanium-based endosseous implants with high antibacterial and osseointegration activities are extremely required in clinics. To achieve this line, herein the doped coatings with three kinds of Zn doses were micro-arc oxidized (MAOed) on Ti. They were examined to reveal a bilayered structure, in which the outer layer consisted completely of the amorphism comprising elements of Ti, O and Zn with Zn doped in the form of weaken Zn-O bonds, and the underlying layer was partially crystallized with nanocrystalline TiO2 and Zn2TiO4 to embed an amorphous matrix. While the Zn doped doses of the surface amorphous layers increased with elevating the MAOed voltages, the weaken Zn-O bonds in the amorphism were identified to act as both the contributor of Zn2+ controllable release and the generator of reactive oxide species (ROS) on the coatings. The enhanced HO• and O2-• formation on the elevated voltage MAOed coatings caused serious break of the cell walls and plasma membranes of S. aureus. In parallel, the enhanced Zn2+ release and extracellular H2O2 formation led to the enhanced intracellular ROS level of S. aureus, further aggravating the damage of plasma membrane, resulting in bacteria death. On contrary to the overdose of Zn doped coating, the moderate doses of Zn doped coatings did not induce additional intracellular ROS and attenuate viability and proliferation of osteoblasts in vitro, and promoted osseointegration in both S. aureus-uninfected and infected rat tibias, which ascribed to the strong antibacterial activity and un-attenuated cell function of the coatings in the infected case. STATEMENT OF SIGNIFICANCE: (1) The Zn-doped coatings revealed a bilayered structure of the surface layer comprising the Ti, O and Zn constructed amorphism with Zn in the form of weaken Zn-O bonds, and the underlying layer comprising nanocrystalline TiO2 and Zn2TiO4 to embed amorphous matrix. (2) The weaken Zn-O bonds in the amorphism were identified to act as both the contributor of Zn2+ controllable release and the generator of ROS on the coatings. (3) The enhanced Zn2+ release and ROS formation on the coatings killed S. aureus by inducing serious break of their cell walls and plasma membranes. This effect in combination of un-attenuated osteoblast proliferation endowed the moderate Zn doped coatings with enhanced osseointegration in S. aureus-infected rat tibias.

中文翻译：

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ROS诱导无定形Zn掺杂的二氧化钛涂层的杀菌活性，并在细菌感染的大鼠胫骨中增强骨整合。

临床上非常需要具有高抗菌和骨整合活性的钛基骨内植入物。为了达到这条线，本文将具有三种锌剂量的掺杂涂层在Ti上进行微弧氧化（MAOed）。检查它们以发现双层结构，其中外层完全由非晶态组成，该非晶态包括Ti，O和Zn元素，并以弱Zn-O键的形式掺杂了Zn，下层部分被纳米晶TiO2结晶。和Zn2TiO4嵌入非晶基质。尽管随着MAOed电压的升高，表面非晶层的Zn掺杂剂量增加，但非晶态中弱的Zn-O键被确定为Zn2 +可控释放的贡献者和反应性氧化物种（ROS）的产生者。涂料。高压MAOed涂层上增强的HO•和O2-•形成导致金黄色葡萄球菌的细胞壁和质膜严重破裂。同时，增加的Zn2 +释放和细胞外H2O2的形成导致金黄色葡萄球菌的细胞内ROS水平增强，进一步加剧了质膜的损伤，导致细菌死亡。与过量掺杂锌的涂层相反，适量的掺杂锌的涂层不会在体外诱导额外的细胞内ROS并减弱成骨细胞的活力和增殖，并促进了未感染金黄色葡萄球菌和感染的大鼠胫骨的骨整合。在感染的情况下对涂层具有很强的抗菌活性和未减弱的细胞功能。重要性声明：（1）掺杂锌的涂层显示出双层结构的表面层，该表面层由Ti，O和Zn构成的无定形结构，具有弱化Zn-O键形式的Zn，下层包含纳米晶TiO2和Zn2TiO4，以嵌入非晶基质。（2）非晶态中弱的Zn-O键被认为既是Zn2 +可控释放的贡献者，又是涂层上ROS的产生者。（3）涂层上Zn2 +释放的增强和ROS的形成通过诱导其细胞壁和质膜的严重破坏而杀死了金黄色葡萄球菌。这种作用与未减毒的成骨细胞增殖相结合，使金黄色葡萄球菌感染的大鼠胫骨中度锌掺杂涂层的骨整合增强。底层包含纳米晶态的TiO2和Zn2TiO4，以嵌入非晶基体。（2）非晶态中弱的Zn-O键被认为既是Zn2 +可控释放的贡献者，又是涂层上ROS的产生者。（3）涂层上Zn2 +释放的增强和ROS的形成通过诱导其细胞壁和质膜的严重破坏而杀死了金黄色葡萄球菌。这种作用与未减毒的成骨细胞增殖相结合，使金黄色葡萄球菌感染的大鼠胫骨中度锌掺杂涂层的骨整合增强。底层包含纳米晶态的TiO2和Zn2TiO4，以嵌入非晶基体。（2）非晶态中弱的Zn-O键被认为既是Zn2 +可控释放的贡献者，又是涂层上ROS的产生者。（3）涂层中Zn2 +释放的增强和ROS的形成通过诱导其细胞壁和质膜的严重破坏而杀死了金黄色葡萄球菌。这种作用与未减弱的成骨细胞增生相结合，使金黄色葡萄球菌感染的大鼠胫骨中度锌掺杂涂层的骨整合增强。（3）涂层中Zn2 +释放的增强和ROS的形成通过诱导其细胞壁和质膜的严重破坏而杀死了金黄色葡萄球菌。这种作用与未减毒的成骨细胞增殖相结合，使金黄色葡萄球菌感染的大鼠胫骨中度锌掺杂涂层的骨整合增强。（3）涂层上Zn2 +释放的增强和ROS的形成通过诱导其细胞壁和质膜的严重破坏而杀死了金黄色葡萄球菌。这种作用与未减毒的成骨细胞增殖相结合，使金黄色葡萄球菌感染的大鼠胫骨中度锌掺杂涂层的骨整合增强。