Li Tao, Wang Na, Chen Su, Lu Ran, Li Hongyi, Zhang Zhenting
Department of Prosthodontics, School of Stomatology, Capital Medical University.
Key Laboratory of Advanced Functional Materials, School of Materials and Engineering, Beijing University of Technology. Beijing, People's Republic of China.
Int J Nanomedicine. 2017 Apr 12;12:2995-3007. doi: 10.2147/IJN.S128775. eCollection 2017.
Prevention of implant-associated infections at an early stage of surgery is highly desirable for the long-term efficacy of implants in dentistry and orthopedics. Infection prophylaxis using conventional antibiotics is becoming less effective due to the development of bacteria resistant to multiple antibiotics. An ideal strategy to conquer bacterial infections is the local delivery of antibacterial agents. Therefore, antimicrobial peptide (AMP) eluting coatings on implant surfaces is a promising alternative. In this study, the feasibility of utilizing TiO nanotubes (TNTs), processed using anodization, as carriers to deliver a candidate AMP on titanium surfaces for the prevention of implant-associated infections is assessed. The broad-spectrum GL13K (GKIIKLKASLKLL-CONH2) AMP derived from human parotid secretory protein was selected and immobilized to TNTs using a simple soaking technique. Field emission scanning electron microscope, X-ray diffraction, Fourier transform infrared spectroscopy, and liquid chromatography-mass spectrometry analyses confirmed the successful immobilization of GL13K to anatase TNTs. The drug-loaded coatings demonstrated a sustained and slow drug release profile in vitro and eradicated the growth of and within 5 days of culture, as assessed by disk-diffusion assay. The GL13K-immobilized TNT (GL13K-TNT) coating demonstrated greater biocompatibility, compared with a coating produced by incubating TNTs with equimolar concentrations of metronidazole. GL13K-TNTs produced no observable cytotoxicity to preosteoblastic cells (MC3T3-E1). The coating may also have an immune regulatory effect, in support of rapid osseointegration around implants. Therefore, the combination of TNTs and AMP GL13K may achieve simultaneous antimicrobial and osteoconductive activities.
在牙科和骨科领域,从手术早期就预防植入物相关感染对于植入物的长期疗效非常重要。由于对多种抗生素具有抗性的细菌的出现,使用传统抗生素进行感染预防的效果越来越差。攻克细菌感染的理想策略是局部递送抗菌剂。因此,在植入物表面涂覆抗菌肽(AMP)洗脱涂层是一种很有前景的替代方法。在本研究中,评估了利用阳极氧化处理的TiO纳米管(TNTs)作为载体在钛表面递送候选AMP以预防植入物相关感染的可行性。选择了源自人腮腺分泌蛋白的广谱GL13K(GKIIKLKASLKLL-CONH2)AMP,并使用简单的浸泡技术将其固定在TNTs上。场发射扫描电子显微镜、X射线衍射、傅里叶变换红外光谱和液相色谱-质谱分析证实GL13K成功固定在锐钛矿型TNTs上。通过圆盘扩散试验评估,载药涂层在体外显示出持续且缓慢的药物释放曲线,并在培养5天内消除了金黄色葡萄球菌和大肠杆菌的生长。与用等摩尔浓度甲硝唑孵育TNTs产生的涂层相比,固定有GL13K的TNT(GL13K-TNT)涂层表现出更高的生物相容性。GL13K-TNTs对前成骨细胞(MC3T3-E1)没有明显的细胞毒性。该涂层还可能具有免疫调节作用,有助于植入物周围的快速骨整合。因此,TNTs和AMP GL13K的组合可能实现同时的抗菌和骨传导活性。