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抗菌肽修饰的分层抗污聚合物刷在功能化导管表面的应用。

Antimicrobial Peptide-Conjugated Hierarchical Antifouling Polymer Brushes for Functionalized Catheter Surfaces.

机构信息

State Key Laboratory of Chemical Resource Engineering, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education, Beijing Laboratory of Biomedical Materials , Beijing University of Chemical Technology , Beijing 100029 , China.

出版信息

Biomacromolecules. 2019 Nov 11;20(11):4171-4179. doi: 10.1021/acs.biomac.9b01060. Epub 2019 Oct 17.

DOI:10.1021/acs.biomac.9b01060
PMID:31596574
Abstract

Catheter-related infection is a great challenge to modern medicine, which causes significant economic burden and increases patient morbidity. Hence, there is a great requirement for functionalized surfaces with inherently antibacterial properties and biocompatibility that prevent bacterial colonization and attachment of blood cells. Herein, we developed a strategy for constructing polymer brushes with hierarchical architecture on polyurethane (PU) via surface-initiated atom-transfer radical polymerization (SI-ATRP). Surface-functionalized PU (PU-DMH) was readily prepared, which comprised of poly(3-[dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azaniumyl]propane-1-sulfonate) (PDMAPS) brushes as the lower layer and antimicrobial peptide-conjugated poly(methacrylic acid) (PMAA) brushes as the upper layer. The PU-DMH surface showed excellent bactericidal property against both Gram-positive and Gram-negative bacteria and could prevent accumulation of bacterial debris on surfaces. Simultaneously, the PU-DMH samples possessed good hemocompatibility and low cytotoxicity. Furthermore, the integrated antifouling and bactericidal properties of PU-DMH under hydrodynamic conditions were confirmed by an in vitro circulating model. The functionalized surface possessed persistent antifouling and bactericidal performances both under static and hydrodynamic conditions. The microbiological and histological results of animal experiments also verified the in vivo anti-infection performance. The present work might find promising clinical applications for preventing catheter-related infection.

摘要

导管相关性感染是现代医学面临的一大挑战,它会造成巨大的经济负担,并增加患者的发病率。因此,人们迫切需要具有固有抗菌性能和生物相容性的功能化表面,以防止细菌定植和血细胞黏附。在此,我们通过表面引发原子转移自由基聚合(SI-ATRP),开发了一种在聚氨酯(PU)上构建具有分级结构的聚合物刷的策略。表面功能化的 PU(PU-DMH)很容易制备,它由聚[3-[[二甲基-[2-(2-甲基-2-丙烯酰氧基)乙基]铵基]丙基]-1-磺酸酯](PDMAPS)刷作为下层和抗菌肽接枝的聚(甲基丙烯酸)(PMAA)刷作为上层组成。PU-DMH 表面对革兰氏阳性菌和革兰氏阴性菌均具有优异的杀菌性能,并能防止细菌碎片在表面堆积。同时,PU-DMH 样品具有良好的血液相容性和低细胞毒性。此外,通过体外循环模型证实了 PU-DMH 在流体动力学条件下的综合抗污和杀菌性能。该功能化表面在静态和动态条件下均具有持久的抗污和杀菌性能。动物实验的微生物学和组织学结果也验证了其体内抗感染性能。本工作可能为预防导管相关性感染提供有前景的临床应用。

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