摘要
Chronic wounds experiencing infections with multidrug-resistant bacteria can be fatal,and in severe cases can lead to sepsis.Antimicrobial peptides are widely used in the field of wound care for their broad-spectrum antibacterial properties and good anti-drug resistance.We prepared bacterial cell membrane chromatography(BCMC)by extracting cell membranes of bacteria using SiO_(2)microspheres as stationary phase.A library of antimicrobial peptides was synthesized in solid phase and screened by BCMC to identify the antimicrobial peptide LKAHR(later named LS5),which is characterized by biosafety,broad-spectrum antibacterial activity,and drug resistance,and a gelatin-based antimicrobial hydrogel(LS5-gel)was prepared to be better applied to wounds.LS5-gel was found to have good in vivo bactericidal properties as well as the ability to promote wound healing in a wound healing model.In the sepsis model,LS5 was found to have a significant inhibitory effect on sepsis infection.It is important for the selection of next-generation antimicrobial drugs and the treatment of chronic wound healing.
慢性伤口遭遇多药耐药菌感染是致命的,严重者会引发脓毒症.抗菌肽的广谱抗菌特性和良好的抗耐药性被广泛用于伤口护理领域.我们以SiO_(2)微球为固定相,提取细菌的细胞膜制备细菌细胞膜色谱(BCMC).固相法合成抗菌肽文库并经BCMC筛选出抗菌肽LKAHR(简称LS5).LS5具有生物安全、广谱抗菌以及抗耐药性等特点,制备明胶基抗菌水凝胶(LS5-gel)以更好应用于伤口.在伤口愈合模型中发现LS5-gel具有良好的体内杀菌性能以及促进伤口愈合能力.在脓毒症模型中发现LS5对脓毒症感染具有明显的抑制作用.本工作对下一代抗菌药物的选取及慢性伤口愈合治疗具有重要指导意义.
作者
Zekai Ren
Xin Ding
Yumei Wang
Han Wu
Xin Liu
Yang Cao
Hailin Cong
Youqing Shen
Bing Yu
任泽凯;丁鑫;王玉梅;吴晗;刘鑫;曹阳;丛海林;申有青;于冰(College of Chemistry and Chemical Engineering,College of Materials Science and Engineering,Institute of Biomedical Materials and Engineering,Qingdao University,Qingdao 266071,China;State Key Laboratory of Bio-Fibers and Eco-Textiles,Qingdao University,Qingdao 266071,China;School of Materials Science and Engineering,Shandong University of Technology,Zibo 255000,China;Key Laboratory of Biomass Chemical Engineering of Ministry of Education,Center for Bionanoengineering,and Department of Chemical and Biological Engineering,Zhejiang University,Hangzhou 310027,China)
基金
supported by the National Natural Science Foundation of China(22074072 and 22274083)
Shandong Provincial Natural Science Foundation(ZR2022LZY022 and ZR2023LZY005)
the Science and Technology Planning Project of South District of Qingdao City(2022-4-005-YY)
the Exploration project of the State Key Laboratory of BioFibers and EcoTextiles of Qingdao University(TSKT202101)
the National Key R&D Program of China(2024YFE0104100)
the Medical Plus Key Project of Qingdao University(YX2024201)。
