State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China; College of Life Science, University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
Biomaterials. 2018 Sep;178:351-362. doi: 10.1016/j.biomaterials.2018.05.008. Epub 2018 May 9.
Implants decorated with antimicrobial peptides (AMPs) can prevent infection and reduce the risk of creating antibiotic resistance. Yet the restricted mobility of surficial AMP often compromises its activity. Here, we report a simple but effective strategy to allow a more flexible display of AMP on the biomaterial surface and demonstrate its efficacy for wound healing. The AMP, tachyplesin I (Tac), is tagged with the polyhydroxyalkanoate-granule-associated protein (PhaP) and immobilized on haloarchaea-produced poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) via hydrophobic interaction. The PhaP-Tac coating effectively inhibits the growth of both Gram-negative and Gram-positive bacteria. It also increases the surface hydrophilicity to improve fibroblast proliferation in vitro, and accelerates wound healing by decreasing bacterial counts to below 10 CFU per gram of tissue in a deep-wound mouse model in vivo. Taken together, these findings demonstrate an effective strategy to realize the full potential of AMPs in imparting implants with an anti-microbial activity that is localized and potent.
经抗菌肽(AMPs)修饰的植入物可以预防感染并降低产生抗生素耐药性的风险。然而,表面 AMP 的受限迁移性常常损害其活性。在这里,我们报告了一种简单但有效的策略,可在生物材料表面更灵活地展示 AMP,并证明其在伤口愈合方面的功效。抗菌肽 tachyplesin I (Tac) 与聚羟基烷酸酯颗粒相关蛋白(PhaP)连接,并通过疏水相互作用固定在盐杆菌产生的聚(3-羟基丁酸酯-co-3-羟基戊酸酯)(PHBHV)上。PhaP-Tac 涂层可有效抑制革兰氏阴性菌和革兰氏阳性菌的生长。它还增加了表面亲水性,以促进体外成纤维细胞增殖,并通过降低细菌数量来加速伤口愈合,在体内深伤口小鼠模型中,组织每克细菌数降至 10 CFU 以下。总之,这些发现表明了一种有效的策略,可以充分发挥 AMP 在赋予植入物局部和强效抗菌活性方面的潜力。