Dressing Blood-Contacting Materials by a Stable Hydrogel Coating with Embedded Antimicrobial Peptides for Robust Antibacterial and Antithrombus Properties

Antimicrobial peptides are an abundant and diverse group of molecules that are produced by many tissues and cell types in a variety of invertebrate, plant and animal species. Their amino acid composition, amphipathicity, cationic charge and size allow them to attach to and insert into membrane bilayers to form pores by 'barrel-stave', 'carpet' or 'toroidal-pore' mechanisms. Although these models are helpful for defining mechanisms of antimicrobial peptide activity, their relevance to how peptides damage and kill microorganisms still need to be clarified. Recently, there has been speculation that transmembrane pore formation is not the only mechanism of microbial killing. In fact several observations suggest that translocated peptides can alter cytoplasmic membrane septum formation, inhibit cell-wall synthesis, inhibit nucleic-acid synthesis, inhibit protein synthesis or inhibit enzymatic activity. In this review the different models of antimicrobial-peptide-induced pore formation and cell killing are presented.

Accelerating growth and global expansion of antimicrobial resistance has deepened the need for discovery of novel antimicrobial agents. Antimicrobial peptides have clear advantages over conventional antibiotics which include slower emergence of resistance, broad-spectrum antibiofilm activity, and the ability to favourably modulate the host immune response. Broad bacterial susceptibility to antimicrobial peptides offers an additional tool to expand knowledge about the evolution of antimicrobial resistance. Structural and functional limitations, combined with a stricter regulatory environment, have hampered the clinical translation of antimicrobial peptides as potential therapeutic agents. Existing computational and experimental tools attempt to ease the preclinical and clinical development of antimicrobial peptides as novel therapeutics. This Review identifies the benefits, challenges, and opportunities of using antimicrobial peptides against multidrug-resistant pathogens, highlights advances in the deployment of novel promising antimicrobial peptides, and underlines the needs and priorities in designing focused development strategies taking into account the most advanced tools available.

In this review we attempt to clarify the notion of what is meant by the term antibacterial surfaces and categorise the approaches that are commonly used in the design of antibacterial surfaces. Application of surface coatings and the modification of the surface chemistry of substrata are generally considered to be a chemical approach to surface modification (as are surface polymerisation, functionalisation, and derivatisation), whereas, modification of the surface architecture of a substrate can be considered a physical approach. Here, the antifouling and bactericidal effects of antibacterial surfaces are briefly discussed. Finally, several recent efforts to design a new generation of antibacterial surfaces, which are based on mimicking the surface nanotopography of natural surfaces, are considered. Copyright © 2013 Elsevier Ltd. All rights reserved.