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Rationally designed dual functional block copolymers for bottlebrush-like coatings: In vitro and in vivo antimicrobial, antibiofilm, and antifouling properties

机译:合理设计的奶瓶刷样涂层的双官能嵌段共聚物:体外和体内抗菌剂,抗菌器和防污性能

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摘要

Graphical abstract Dual functional PEGylated cationic polypeptides diblock copolymers were synthesized and forming a bottlebrush-like coating on silicone surface. It exhibits potent in vitro and in vivo contact-active antimicrobial, antibiofilm efficacy, and protein/platelet resist activity. Additionally, this coating has excellent blood compatibility, as well as low cytotoxicity. Display Omitted Abstract Numerous antimicrobial coatings have been developed for biomedical devices/implants, but few can simultaneously fulfill the requirements for antimicrobial and antifouling ability and biocompatibility. In this study, to develop an antimicrobial and antibiofilm surface coating, diblock amphiphilic molecules with antimicrobial and antifouling segments in a single chain were rationally designed and synthesized. Cationic antimicrobial polypeptides (AMP) were first synthesized by N -carboxyanhydride ring-opening polymerization (NCA-ROP). Heterofunctionalized poly(ethylene glycol) with different lengths (methacrylate-PEG n - tosyl , n = 10/45/90) was synthesized and site-specifically conjugated with polypeptides to form diblock amphiphiles. Along with increased PEG chain length, hemolytic activity was considerably improved, and broad-spectrum antimicrobial activity is retained. Three MA-PEG n - b -AMP copolymers were further grafted onto the surface of silicone rubber (a commonly used catheter material) via plasma/UV-induced surface polymerizations to form a bottlebrush-like coating with excellent antimicrobial activity against several pathogenic bacteria ( Escherichia coli , Pseudomonas aeruginosa , and Staphylococcus aureus ), and effectively prevent biofilm formation. This bottlebrush coating also greatly reduced protein adsorption and platelet adhesion, indicating its excellent antifouling ability. An in vitro cytotoxicity study also demonstrated that this coating is biocompatible with mammalian cells. After subcutaneous implantation of the materials in rats, we demonstrated that the g -PEG 45 - b -AMP bottlebrush coating exhibits significant anti-infective activity in vivo . Thus, this facilely synthesized PEGylated AMP bottlebrush coating is a feasible method to prevent biomedical devices-associated infections. Statement of Significance Current antimicrobial coatings are often associated with concerns such as antibiotic resistance, environmental pollution, short-time antimicrobial activity, biofouling, poor blood compatibility and cytotoxicity, etc . To overcome these drawbacks, a robust PEGylated cationic amphiphilic peptides-based bottlebrush-like surface coating is demonstrated here, which fulfil the requirements of antimicrobial and antifouling as well as biocompatibility in the meantime. Briefly, the rational designed g -PEG n - b -AMP block copolymers (n = 10/45/90) were synthesized and grafted on silicone surface. This bottlebrush-like coating efficiently kill the contacted bacteria and prevent the biofilm formation, greatly reduced protein and platelet adhesion. It also exhibits excellent blood compatibility and low cytotoxicity in vitro . In particular, g -PEG 45 - b -AMP coating exhibits significant anti-infection effect in vivo . This coating offering an effective strategy for combating biomedical devices-associated infections.
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著录项

  • 来源
    《Acta biomaterialia》 |2017年第1期|共13页
  • 作者单位

    Center for Biomedical Engineering and Regenerative Medicine Frontier Institute of Science and;

    Center for Biomedical Engineering and Regenerative Medicine Frontier Institute of Science and;

    Center for Biomedical Engineering and Regenerative Medicine Frontier Institute of Science and;

    Center for Biomedical Engineering and Regenerative Medicine Frontier Institute of Science and;

    Center for Biomedical Engineering and Regenerative Medicine Frontier Institute of Science and;

    Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM) Jiangsu;

    Department of Biomedical Engineering University of Michigan;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 普通生物学;
  • 关键词

    Antimicrobial polypeptides; Surface coating; Antifouling; Antibiofilm; Polymer bottlebrush;

    机译:抗微生物多肽;表面涂层;防污;抗体;聚合物吹瓶;

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