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具有电化学结合强力霉素的生物活性植入物表面在体外和体内均可促进骨形成标志物的产生。

Bioactive implant surface with electrochemically bound doxycycline promotes bone formation markers in vitro and in vivo.

作者信息

Walter M S, Frank M J, Satué M, Monjo M, Rønold H J, Lyngstadaas S P, Haugen H J

机构信息

Department of Biomaterials, Institute for Clinical Dentistry, University of Oslo, Oslo, Norway; Institute of Medical and Polymer Engineering, Chair of Medical Engineering, Technische Universität München, Garching, Germany.

Department of Fundamental Biology and Health Sciences, Research Institute on Health Sciences (IUNICS), University of Balearic Islands, Palma de Mallorca, Spain.

出版信息

Dent Mater. 2014 Feb;30(2):200-14. doi: 10.1016/j.dental.2013.11.006. Epub 2013 Dec 27.

DOI:10.1016/j.dental.2013.11.006
PMID:24377939
Abstract

OBJECTIVES

The objective of this study was to demonstrate a successful binding of Doxy hyclate onto a titanium zirconium alloy surface.

METHODS

The coating was done on titanium zirconium coins in a cathodic polarization setup. The surface binding was analyzed by SEM, SIMS, UV-vis, FTIR and XPS. The in vitro biological response was tested with MC3T3-E1 murine pre-osteoblast cells after 14 days of cultivation and analyzed in RT-PCR. A rabbit tibial model was also used to confirm its bioactivity in vivo after 4 and 8 weeks healing by means of microCT.

RESULTS

A mean of 141 μg/cm(2) of Doxy was found firmly attached and undamaged on the coin. Inclusion of Doxy was documented up to a depth of approximately 0.44 μm by tracing the (12)C carbon isotope. The bioactivity of the coating was documented by an in vitro study with murine osteoblasts, which showed significantly increased alkaline phosphatase and osteocalcin gene expression levels after 14 days of cell culture along with low cytotoxicity. Doxy coated surfaces showed increased bone formation markers at 8 weeks of healing in a rabbit tibial model.

SIGNIFICANCE

The present work demonstrates a method of binding the broad spectrum antibiotic doxycycline (Doxy) to an implant surface to improve bone formation and reduce the risk of infection around the implant. We have demonstrated that TiZr implants with electrochemically bound Doxy promote bone formation markers in vitro and in vivo.

摘要

目的

本研究的目的是证明多西环素盐酸盐成功结合到钛锆合金表面。

方法

在阴极极化装置中对钛锆硬币进行涂层处理。通过扫描电子显微镜(SEM)、二次离子质谱(SIMS)、紫外可见光谱(UV-vis)、傅里叶变换红外光谱(FTIR)和X射线光电子能谱(XPS)分析表面结合情况。在培养14天后,用MC3T3-E1小鼠前成骨细胞测试体外生物学反应,并通过逆转录聚合酶链反应(RT-PCR)进行分析。还使用兔胫骨模型,通过微型计算机断层扫描(microCT)在愈合4周和8周后确认其体内生物活性。

结果

发现平均141μg/cm²的多西环素牢固附着在硬币上且未受损。通过追踪(12)C碳同位素,记录到多西环素的掺入深度约为0.44μm。用小鼠成骨细胞进行的体外研究证明了涂层的生物活性,该研究表明细胞培养14天后碱性磷酸酶和骨钙素基因表达水平显著增加,且细胞毒性较低。在兔胫骨模型中,多西环素涂层表面在愈合8周时显示出骨形成标志物增加。

意义

本研究展示了一种将广谱抗生素多西环素(Doxy)结合到植入物表面以改善骨形成并降低植入物周围感染风险的方法。我们已经证明,电化学结合多西环素的TiZr植入物在体外和体内均能促进骨形成标志物的产生。

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