Department of Orthopedics, The Affiliated Yiwu Hospital of Wenzhou Medical University, Yiwu, Zhejiang, 322000, People's Republic of China.
Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People's Republic of China.
Int J Nanomedicine. 2021 Apr 21;16:2983-2994. doi: 10.2147/IJN.S299154. eCollection 2021.
Bone infections remain one of the most common and serious complications of orthopedic surgery, posing a tremendous economic burden to society and patients. This is because bacteria colonize and multiply on the surface of the implant. The (MMT/PLL) multilayer films have been shown to effectively release antibiotics depending on the changes in the microenvironment. Here, vancomycin was loaded into the (MMT/PLL) multilayer films, which were prepared to be used as a local delivery system for the treatment of bone infections.
We used the layer-by-layer self-assembly method to prepare VA-loaded coatings (MMT/PLL-VA) consisting of montmorillonite (MMT), poly-L-lysine (PLL), and VA. The thickness and surface morphology of coatings were characterized using spectroscopic ellipsometry and scanning electron microscopy (SEM). In order to evaluate the drug release behavior from coatings in different media, we measured the size of the zone of inhibition. Additionally, in vitro antibacterial activity was assessed using the shake-flask culture method and SEM images, while that of in vivo was evaluated by establishing an animal model of bone infection.
Our findings revealed that small-molecule antibiotics were successfully loaded into the (MMT/PLL-VA) multilayer film structure during the hierarchical self-assembly process and subsequently the multilayer film structure depicted linear growth behavior. The PLL in the multilayer films was progressively degraded which triggered the VA release when contacted with CMS or bacterial infections. The release of VA from multilayer film structure depends on the concentration changes of CMS. Notably, the multilayer films presented great in vitro cell compatibility. Moreover, the prepared antibacterial multilayer films showed excellent antibacterial property by killing more than 99.99% of in 24 h. More importantly, we found that multilayer film exhibits good sterilization effect and biocompatibility under the stimulation of bacterial liquid both in vitro and in vivo antibacterial ability tests.
Altogether, this study shows that (MMT/PLL-VA) multilayer films containing CMS and bacteria-responsive drug release properties posess high bactericidal activity and good biocompatibility. This finding provides a novel strategy for the treatment of bone infections.
骨骼感染仍然是骨科手术中最常见和最严重的并发症之一，给社会和患者带来了巨大的经济负担。这是因为细菌在植入物表面定植和繁殖。研究表明，（MMT/PLL）多层膜可以根据微环境的变化有效地释放抗生素。在这里，万古霉素被载入（MMT/PLL）多层膜中，被制备成用于治疗骨骼感染的局部递送系统。
我们使用层层自组装的方法制备了由蒙脱石（MMT）、聚-L-赖氨酸（PLL）和万古霉素组成的负载万古霉素的涂层（MMT/PLL-VA）。使用光谱椭圆术和扫描电子显微镜（SEM）来表征涂层的厚度和表面形态。为了评估涂层在不同介质中的药物释放行为，我们测量了抑菌圈的大小。此外，通过摇瓶培养法和 SEM 图像评估了体外抗菌活性，通过建立动物骨骼感染模型评估了体内抗菌活性。
研究结果表明，在分层自组装过程中，小分子抗生素成功地载入到（MMT/PLL-VA）多层膜结构中，随后多层膜结构呈现线性生长行为。当接触 CMS 或细菌感染时，多层膜中的 PLL 逐渐降解，触发 VA 的释放。VA 从多层膜结构中的释放取决于 CMS 的浓度变化。值得注意的是，多层膜具有良好的体外细胞相容性。此外，所制备的抗菌多层膜在 24 小时内杀死了超过 99.99%的，表现出优异的抗菌性能。更重要的是，我们发现，在体外和体内抗菌能力测试中，多层膜在细菌液的刺激下具有良好的杀菌效果和生物相容性。
总之，这项研究表明，含有 CMS 和细菌响应性药物释放特性的（MMT/PLL-VA）多层膜具有高杀菌活性和良好的生物相容性。这一发现为治疗骨骼感染提供了一种新策略。
