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选择性激光熔化多孔金属植入物固定的银纳米颗粒可以杀死并防止耐甲氧西林金黄色葡萄球菌形成生物膜。

Selective laser melting porous metallic implants with immobilized silver nanoparticles kill and prevent biofilm formation by methicillin-resistant Staphylococcus aureus.

机构信息

Department of Biomechanical Engineering, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD, Delft, The Netherlands; Additive Manufacturing Lab, Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD, Delft, The Netherlands.

Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

出版信息

Biomaterials. 2017 Sep;140:1-15. doi: 10.1016/j.biomaterials.2017.02.030. Epub 2017 Feb 28.

Abstract

Implant-associated infection and limited longevity are two major challenges that orthopedic devices need to simultaneously address. Additively manufactured porous implants have recently shown tremendous promise in improving bone regeneration and osseointegration, but, as any conventional implant, are threatened by infection. In this study, we therefore used rational design and additive manufacturing in the form of selective laser melting (SLM) to fabricate porous titanium implants with interconnected pores, resulting in a 3.75 times larger surface area than corresponding solid implants. The SLM implants were biofunctionalized by embedding silver nanoparticles in an oxide surface layer grown using plasma electrolytic oxidation (PEO) in Ca/P-based electrolytes. The PEO layer of the SLM implants released silver ions for at least 28 days. X-ray diffraction analysis detected hydroxyapatite on the SLM PEO implants but not on the corresponding solid implants. In vitro and ex vivo assays showed strong antimicrobial activity of these novel SLM PEO silver-releasing implants, without any signs of cytotoxicity. The rationally designed SLM porous implants outperformed solid implants with similar dimensions undergoing the same biofunctionalization treatment. This included four times larger amount of released silver ions, two times larger zone of inhibition, and one additional order of magnitude of reduction in numbers of CFU in an ex vivo mouse infection model.

摘要

植入物相关感染和有限的使用寿命是骨科器械需要同时解决的两个主要挑战。最近,增材制造的多孔植入物在改善骨再生和骨整合方面显示出巨大的潜力,但与任何传统植入物一样,它们也受到感染的威胁。在这项研究中,我们因此使用合理的设计和增材制造(选择性激光熔化,SLM)来制造具有互连孔的多孔钛植入物,其表面积比相应的实心植入物大 3.75 倍。SLM 植入物通过在基于 Ca/P 的电解质中使用等离子体电解氧化(PEO)在氧化物表面层中嵌入银纳米颗粒而具有生物功能化。SLM 植入物的 PEO 层至少释放了 28 天的银离子。X 射线衍射分析在 SLM PEO 植入物上检测到了羟基磷灰石,但在相应的实心植入物上没有。体外和体内试验表明,这些新型 SLM PEO 释放银的植入物具有很强的抗菌活性,没有任何细胞毒性的迹象。经过相同的生物功能化处理,具有类似尺寸的合理设计的 SLM 多孔植入物的性能优于实心植入物。这包括释放的银离子数量增加了四倍,抑制区增加了两倍,在体外小鼠感染模型中 CFU 的数量减少了一个数量级。

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