Postoperative infections are the most common complications faced by surgeons after implant surgery. To address this issue, an emerging and promising approach is to develop antimicrobial coatings using antibiotic substitutes. We investigated the use of polycationic homopolypeptides in a layer-by-layer coating combined with hyaluronic acid (HA) to produce an effective antimicrobial shield. The three peptide-based polycations used to make the coatings, poly(l-arginine) (PAR), poly(l-lysine), and poly(l-ornithine), provided an efficient antibacterial barrier by a contact-killing mechanism against Gram-positive, Gram-negative, and antibiotic-resistant bacteria. Moreover, this activity was higher for homopolypeptides containing 30 amino-acid residues per polycation chain, emphasizing the impact of the polycation chain length and its mobility in the coatings to deploy its contact-killing antimicrobial properties. However, the PAR-containing coating emerged as the best candidate among the three selected polycations, as it promoted cell adhesion and epithelial monolayer formation. It also stimulated nitric oxide production in endothelial cells, thereby facilitating angiogenesis and subsequent tissue regeneration. More interestingly, bacteria did not develop a resistance to PAR and (PAR/HA) also inhibited the proliferation of eukaryotic pathogens, such as yeasts. Furthermore, in vivo investigations on a (PAR/HA)-coated hernia mesh implanted on a rabbit model confirmed that the coating had antibacterial properties without causing chronic inflammation. These impressive synergistic activities highlight the strong potential of PAR/HA coatings as a key tool in combating bacteria, including those resistant to conventional antibiotics and associated to medical devices.

There is an urgent need to develop new therapeutic strategies to fight the emergence of multidrug resistant bacteria. Many antimicrobial peptides (AMPs) have been identified and characterized, but clinical translation has been limited partly due to their structural instability and degradability in physiological environments. The use of unnatural backbones leading to foldamers can generate peptidomimetics with improved properties and conformational stability. We recently reported the successful design of urea-based eukaryotic cell-penetrating foldamers (CPFs). Since cell-penetrating peptides and AMPs generally share many common features, we prepared new sequences derived from CPFs by varying the distribution of histidine- and arginine-type residues at the surface of the oligourea helix, and evaluated their activity on both Gram-positive and Gram-negative bacteria as well as on fungi. In addition, we prepared and tested new amphiphilic block cofoldamers consisting of an oligourea and a peptide segment whereby polar and charged residues are located in the peptide segment and more hydrophobic residues in the oligourea segment. Several foldamer sequences were found to display potent antibacterial activities even in the presence of 50% serum. Importantly, we show that these urea-based foldamers also possess promising antifungal properties.

To fight against antibiotic-resistant bacteria adhering and developing on medical devices, which is a growing problem worldwide, researchers are currently developing new "smart" materials and coatings. They consist in delivery of antimicrobial agents in an intelligent way, i.e., only when bacteria are present. This requires the use of new and sophisticated tools combining antimicrobial agents with lipids or polymers, synthetic and/or natural. In this review, three classes of innovative materials are described: hydrogels, nanomaterials, and thin films. Moreover, smart antibacterial materials can be classified into two groups depending on the origin of the stimulus used: those that respond to a nonbiological stimulus (light, temperature, electric and magnetic fields) and those that respond to a biological stimulus related to the presence of bacteria, such as changes in pH or bacterial enzyme secretion. The bacteria presence can induce a pH change that constitutes a first potential biological trigger allowing the system to become active. A second biological trigger signal consists in enzymes produced by bacteria themselves. A complete panel of recent studies will be given focusing on the design of such innovative smart materials that are sensitive to biological triggers.

The number of nosocomial infections related to implants and medical devices increase alarmingly worldwide. New strategies based on the design of antimicrobial coatings are required to prevent such infections. Polyelectrolyte "multilayer" films constitute a powerful tool for nanoscale surface functionalization which allows addressing this issue. By investigating films built up with poly(arginine) (PAR) of various chain lengths (10, 30, 100, and 200 residues) and hyaluronic acid (HA), we demonstrate that exclusively films constructed with poly(arginine) composed of 30 residues (PAR30) acquire a strong antimicrobial activity against Gram-positive and Gram-negative pathogenic bacteria associated with infections of medical devices. This chain-size effect is extremely striking and is the first example reported where the length of the polyelectrolytes played a key-role in the functionality of the films. Moreover, this unexpected functionality of nanolayered polypeptide/polysaccharide PAR30/HA films occurs without adding any specific antimicrobial agent, such as antibiotics or antimicrobial peptides. PAR30/HA film inhibits bacteria through a contact-killing mechanism due to the presence of mobile PAR30 chains. These chains are assumed to diffuse toward the interface, where they interact with the bacteria with the consequence of killing them. This new coating with unique properties based on the association of a homopolypeptide of 30 residues with a polysaccharide constitutes a simple system to prevent implant-related infections with a reasonable production cost.