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具有β-防御素-14 的多功能磺化聚醚醚酮涂层,可产生持久和广谱的抗菌活性和骨整合。

Multifunctional sulfonated polyetheretherketone coating with beta-defensin-14 for yielding durable and broad-spectrum antibacterial activity and osseointegration.

机构信息

Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, PR China.

出版信息

Acta Biomater. 2019 Mar 1;86:323-337. doi: 10.1016/j.actbio.2019.01.016. Epub 2019 Jan 11.

Abstract

To address periprosthetic joint infection (PJI), a formidable complication after joint arthroplasty, an implant with excellent osseointegration and effective antibacterial activity has being extensively pursued and developed. In this work, the mouse beta-defensin-14 (MBD-14) was immobilized on the polyetheretherketone (PEEK) surface with three-dimensional (3D) porous structure to improve its antibacterial activity and osseointegration. An in vitro antibacterial evaluation showed that the porous PEEK loaded with MBD-14 wages a durable and effective fight against both Staphylococcus aureus (gram-positive) and Pseudomonas aeruginosa (gram-negative). In addition to the superior antibacterial activity, we found that the enhanced proliferation and osteogenic differentiation of bone mesenchymal stem cells were verified through various in vitro analyses. To evaluate the in vivo bactericidal effect and osseointegration of the samples, the rat femoral models with infection and non-infection were established. The enhanced osseointegration of the MBD-14-loaded samples was found in both two in vivo models. And no bacteria survived on the surfaces of samples with a relatively high MBD-14 concentration. Above results indicate that the 3D porous PEEK coating loaded with MBD-14 simultaneously yields excellent osseointegration while exerting durable and broad-spectrum antibacterial activity. And it paves the way for PEEK to be applied clinically to address PJI. STATEMENT OF SIGNIFICANCE: (1). By using the physio-chemical technique including sulfonation and lyophilization etc., a three-dimensional porous network is developed on polyetheretherketone (PEEK) surface, in which mouse beta-defensin-14 (MBD-14, a broad-spectrum antimicrobial peptide) is then loaded. It endows PEEK with antibacterial activity and osseointegration. (2). Two in vivo animal models with infection and non-infection are used to prove the new bone formation around the samples. (3). Supplementary material also proves that MBD-14 promotes the osteogenic differentiation of BMSCs. However, its potential mechanism needs to be further studied in future. (4). The modified PEEK, including excellent osseointegration and a durable and broad-spectrum antibacterial activity, could be applied clinically to address PJI which is a hot potato for surgeons and patients undergoing total joint arthroplasty.

摘要

为了解决关节置换术后一个严重的并发症——假体周围关节感染(PJI),人们广泛地研究和开发了具有优异的骨整合和有效抗菌活性的植入物。在这项工作中,将小鼠β-防御素-14(MBD-14)固定在具有三维(3D)多孔结构的聚醚醚酮(PEEK)表面上,以提高其抗菌活性和骨整合能力。体外抗菌评价表明,负载 MBD-14 的多孔 PEEK 能够持久有效地对抗金黄色葡萄球菌(革兰氏阳性)和铜绿假单胞菌(革兰氏阴性)。除了卓越的抗菌活性外,我们还通过各种体外分析发现,增强了骨髓间充质干细胞的增殖和成骨分化。为了评估样品的体内杀菌效果和骨整合能力,建立了感染和非感染的大鼠股骨模型。在这两种体内模型中,都发现负载 MBD-14 的样品的骨整合能力得到了增强。并且在高浓度 MBD-14 的样品表面没有细菌存活。上述结果表明,负载 MBD-14 的 3D 多孔 PEEK 涂层同时具有出色的骨整合能力,并且具有持久和广谱的抗菌活性。为 PEEK 在临床上应用于解决 PJI 铺平了道路。

意义陈述

(1). 通过使用物理化学技术(包括磺化和冻干等),在聚醚醚酮(PEEK)表面上开发出三维多孔网络,然后负载小鼠β-防御素-14(MBD-14,一种广谱抗菌肽)。它赋予 PEEK 抗菌活性和骨整合能力。

(2). 使用感染和非感染两种体内动物模型来证明样品周围新骨的形成。

(3). 补充材料还证明 MBD-14 促进了 BMSCs 的成骨分化。但是,其潜在机制需要在未来进一步研究。

(4). 改性 PEEK 具有出色的骨整合能力和持久且广谱的抗菌活性,可应用于临床,解决因全关节置换术而备受外科医生和患者关注的 PJI 问题。

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