Covalent immobilization of antimicrobial peptides (AMPs) onto biomaterial surfaces

Abstract

a b s t r a c tBacterial adhesion to biomaterials remains a major problem in the medical devices field. Antimicrobial peptides (AMPs) are well-known components of the innate immune system that can be applied to overcome biofilm-associated infections. Their relevance has been increasing as a practical alternative to conventional antibiotics, which are declining in effectiveness. The recent interest focused on these peptides can be explained by a group of special features, including a wide spectrum of activity, high efficacy at very low concentrations, target specificity, anti-endotoxin activity, synergistic action with classical antibiotics, and low propensity for developing resistance. Therefore, the development of an antimicrobial coating with such properties would be worthwhile. The immobilization of AMPs onto a biomaterial surface has further advantages as it also helps to circumvent AMPs' potential limitations, such as short half-life and cytotoxicity associated with higher concentrations of soluble peptides. The studies discussed in the current review report on the impact of covalent immobilization of AMPs onto surfaces through different chemical coupling strategies, length of spacers, and peptide orientation and concentration. The overall results suggest that immobilized AMPs may be effective in the prevention of biofilm formation by reduction of microorganism survival post-contact with the coated biomaterial. Minimal cytotoxicity and longterm stability profiles were obtained by optimizing immobilization parameters, indicating a promising potential for the use of immobilized AMPs in clinical applications. On the other hand, the effects of tethering on mechanisms of action of AMPs have not yet been fully elucidated. Therefore, further studies are recommended to explore the real potential of immobilized AMPs in health applications as antimicrobial coatings of medical devices.

Combinatorial discovery of polymers resistant to bacterial attachment

“…Biofilms present on the surface of medical devices provide the bacterial inocula for disease and can also serve as reservoirs of plasmids carrying antibioticresistance genes 4,5 . Most strategies for reducing biofilm-associated infections focus on the modification of existing materials that are used to manufacture in-dwelling medical devices by the incorporation of antibiotics 6,7 or other antimicrobials, such as silver salts, nitrofurazone, chlorhexidine, polymerized quaternary ammonium surfactants, antibacterial peptides and anionic nanoporous hydrogels [8][9][10][11][12][13][14][15] . These approaches aim to kill bacterial cells that attach to a material, but we believe that greater efficacy in preventing biofilm formation might be achieved by the development of new materials that are inherently resistant to biofilm formation 16 .…”

Novel cinnamic acid/4-aminoquinoline conjugates bearing non-proteinogenic amino acids: Towards the development of potential dual action antimalarials

“…The most active vinyl sulfones contained a dipeptide LeuhPhe spacer between a bulky moiety and the S-alkylating motif [9,18e20]. Unfortunately, peptide-based inhibitors are prone to proteolytic degradation [21], a problem that can be overcome by use of suitable peptide delivery systems [22,23]. Still, such systems are likely to impair efficient inhibition of the target enzyme.…”

Antibacterial Properties of hLf1–11 Peptide onto Titanium Surfaces: A Comparison Study Between Silanization and Surface Initiated Polymerization

“…In order to reduce implant failure associated to bacterial infections, the immobilization of antimicrobial peptides (AMPs) onto implant surfaces has been studied 8,9 . In general, AMPs are cationic, often amphipathic, which primarily kill bacteria by interacting and disrupting their cell membrane [10][11][12][13] .…”