title: Rationally designed dual functional block copolymers for bottlebrush-like coatings: In vitro and in vivo antimicrobial, antibiofilm, and antifouling properties.
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-PEGn-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-PEGn-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-PEG45-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.
  
  
  
  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-PEGn-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-PEG45-b-AMP coating exhibits significant anti-infection effect in vivo. This coating offering an effective strategy for combating biomedical devices-associated infections.
authors.affiliation: Center for Biomedical Engineering and Regenerative Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Center for Biomedical Engineering and Regenerative Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Yu
authors.affiliation: Center for Biomedical Engineering and Regenerative Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Su
authors.affiliation: Center for Biomedical Engineering and Regenerative Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Meihua
authors.initials: M
authors.lastname: Xie
authors.affiliation: Center for Biomedical Engineering and Regenerative Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, Nanjing 211816, China. Electronic address: iampli@njtech.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biologic and Materials Sciences, University of Michigan, 1011, North University Ave., Room 2209, Ann Arbor, MI 48109, USA; Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI 48109, USA; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: mapx@umich.edu.
authors.forename: Peter X
authors.initials: PX
authors.lastname: Ma
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000502:physiology*; D006801:Humans; D008422:Materials Testing; D051379:Mice; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D051381:Rats; D013211:Staphylococcus aureus / Q000502:physiology*
chemical_list: D023181:Antimicrobial Cationic Peptides; D020099:Coated Materials, Biocompatible
keywords: Antibiofilm; Antifouling; Antimicrobial polypeptides; Polymer bottlebrush; Surface coating