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锶(Sr)和银(Ag)负载的具有联合成骨诱导和抗菌活性的纳米管状结构。

Strontium (Sr) and silver (Ag) loaded nanotubular structures with combined osteoinductive and antimicrobial activities.

机构信息

Othopeadic Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China; Biomaterials Innovation Research Center, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston 02139, MA, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139, MA, USA.

Othopeadic Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China.

出版信息

Acta Biomater. 2016 Feb;31:388-400. doi: 10.1016/j.actbio.2015.11.046. Epub 2015 Dec 2.

DOI:10.1016/j.actbio.2015.11.046
PMID:26612413
Abstract

UNLABELLED

Two frequent problems are associated with the titanium surfaces of bone/dental implants: lack of native tissue integration and associated infection. These problems have prompted a significant body of research regarding the modification of these surfaces. The present study describes a hydrothermal treatment for the fabrication of strontium (Sr) and silver (Ag) loaded nanotubular structures with different tube diameters on titanium surfaces. The Sr loading from a Sr(OH)2 solution was regulated by the size of the inner diameter of the titanium nanotubes (NT) (30nm or 80nm, formed at 10V or 40V, respectively). The quantity of Ag was adjusted by immersing the samples in 1.5 or 2.0M AgNO3 solutions. Sr and Ag were released in a controllable and prolonged matter from the NT-Ag.Sr samples, with negligible cytotoxicity. Prominent antibacterial activity was observed due to the release of Ag. Sr incorporation enhanced the initial cell adhesion, migration, and proliferation of preosteoblast MC3T3-E1 cells. Sr release also up-regulated the expression of osteogenic genes and induced mineralization, as suggested by the presence of more mineralized calcium nodules in cells cultured on NT-Ag.Sr surfaces. In vivo experiments showed that the Sr-loaded samples accelerated the formation of new bone in both osteoporosis and bone defect models, as confirmed by X-ray, Micro-CT evaluation, and histomorphometric analysis of rats implanted with NT-Ag.Sr samples. The antibacterial activity and outstanding osteogenic properties of NT-Ag.Sr samples highlight their excellent potential for use in clinical applications.

STATEMENT OF SIGNIFICANCE

Two frequent problems associated with Ti surfaces, widely used in orthopedic and dental arenas, are their lack of native tissue integration and risk of infection. We describe a novel approach for the fabrication of strontium (Sr) and silver (Ag) loaded nanotubular structures on titanium surfaces. A relevant aspect of this work is the demonstration of long-lasting and controllable Ag release, leading to excellent antibacterial and anti-adherent properties against methicillin-resistant Staphylococcus aureus (MRSA), and Gram-negative bacteria such as Escherichia coli. The extended release of Sr accelerates the filling of bone defects by improving the repair of damaged cortical bone and increasing trabecular bone microarchitecture. Our results highlight the potential of Sr and Ag loaded nanotubular structures for use in clinical applications.

摘要

未加说明

骨/牙科植入物的钛表面常存在两个问题:缺乏天然组织整合和相关感染。这些问题促使人们对这些表面进行了大量研究,以寻求改进方法。本研究描述了一种在钛表面制备锶(Sr)和银(Ag)负载的纳米管状结构的水热处理方法,不同管状结构的管径不同。通过调节钛纳米管(NT)的内径大小(分别为 30nm 或 80nm,在 10V 或 40V 下形成)来控制 Sr 的负载量来自 Sr(OH)2 溶液。通过将样品浸入 1.5 或 2.0M AgNO3 溶液中,来调节 Ag 的数量。NT-Ag.Sr 样品中的 Sr 和 Ag 以可控且持久的方式释放,几乎没有细胞毒性。由于 Ag 的释放,观察到明显的抗菌活性。Sr 的掺入增强了前成骨细胞 MC3T3-E1 细胞的初始粘附、迁移和增殖。Sr 的释放还上调了成骨基因的表达,并诱导了矿化,这表明在 NT-Ag.Sr 表面培养的细胞中存在更多矿化的钙结节。体内实验表明,负载 Sr 的样品在骨质疏松症和骨缺损模型中均加速了新骨的形成,这通过 X 射线、大鼠植入 NT-Ag.Sr 样品的 Micro-CT 评估和组织形态计量学分析得到证实。NT-Ag.Sr 样品的抗菌活性和出色的成骨性能突出了其在临床应用中的巨大潜力。

意义声明

广泛用于骨科和牙科领域的 Ti 表面存在两个常见问题,即缺乏天然组织整合和感染风险。我们描述了一种在钛表面制备锶(Sr)和银(Ag)负载纳米管状结构的新方法。这项工作的一个相关方面是证明了 Ag 的长效和可控释放,导致对耐甲氧西林金黄色葡萄球菌(MRSA)和革兰氏阴性菌(如大肠杆菌)具有极好的抗菌和抗附着性能。Sr 的持续释放通过改善受损皮质骨的修复和增加小梁骨微结构来加速骨缺损的填充。我们的结果突出了 Sr 和 Ag 负载纳米管状结构在临床应用中的潜力。

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