Beijing Research Institute of Traumatology and Orthopaedics, Beijing 100035, PR China.
Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, PR China.
Mater Sci Eng C Mater Biol Appl. 2019 Jul;100:523-534. doi: 10.1016/j.msec.2019.03.039. Epub 2019 Mar 11.
The release of anti-infection drugs in a targeted and efficient manner in response to the attack time and degree of severity of infection is a requirement of new generation implants. Herein, we design an infection-responsive guided tissue regeneration (GTR)/guided bone regeneration (GBR) membrane based on electrospun nanofibers. Polycaprolactone (PCL) nanofiber mats are coated with polydopamine to endow hydroxyl groups on the surface and then functionalized with siloxane to introduce amino groups. Metronidazole (MNA), an antibiotic drug, is esterified and then grafted onto the surface of the modified PCL nanofiber mats via ester linkages. The ester bonds can be selectively hydrolyzed by cholesterol esterase (CE), an enzyme secreted by macrophagocytes accumulated at the site of infection, whose concentration is positively related to the severity of the infection. The drug can be triggered to release from the nanofiber membranes in responsive to the CE. With the increase of the CE concentration, a higher amount of MNA is released from the nanofiber mat, resulting in the enhancement of the antibacterial capability of the MNA-grafted nanofiber mat. The nanofiber mat has good cytocompatibility. This CE-responsive drug delivery system based on the electrospun nanofiber mat is promising as an optimal choice for antibacterial GTR/GBR membrane.
以抗感染药物的靶向和高效释放来应对感染的发作时间和严重程度,是新一代植入物的要求。在此,我们设计了一种基于静电纺纳米纤维的抗感染响应性引导组织再生(GTR)/引导骨再生(GBR)膜。聚己内酯(PCL)纳米纤维垫用聚多巴胺进行涂覆,在表面赋予羟基,然后用硅氧烷进行功能化,引入氨基。甲硝唑(MNA),一种抗生素药物,通过酯键进行酯化,然后通过酯键接枝到经过修饰的 PCL 纳米纤维垫的表面上。胆固醇酯酶(CE),一种在感染部位积累的巨噬细胞分泌的酶,可以选择性地水解酯键,其浓度与感染的严重程度呈正相关。该药物可以通过 CE 响应触发从纳米纤维膜中释放。随着 CE 浓度的增加,更多的 MNA 从纳米纤维垫中释放出来,从而增强了接枝 MNA 的纳米纤维垫的抗菌能力。纳米纤维垫具有良好的细胞相容性。这种基于静电纺纳米纤维的 CE 响应药物递送系统有望成为抗菌 GTR/GBR 膜的最佳选择。