Preventing infections on medical implants : integration of LL-37, an antimicrobial peptide, in multilayered coatings
(2024)
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- The use of antibacterial agents is essential in the treatment of patients with bacterial infections. However, the last decades have seen an increase in the number of antimicrobial-resistant bacteria, which could have catastrophic consequences. Antimicrobial resistance is highlighted as one of the most serious threats to global health. In addition to this concern, bacterial adhesion and colonization on the surface of medical implantable devices, leading to biofilm formation, are causing severe complications. With a view to finding new effective strategies against these infections, this thesis aims at developing a coating displaying antibiofilm properties, that could be applied to the surface of medical devices. This was achieved through the assembly of multilayers integrating LL-37, an antimicrobial peptide (AMP), using the layer-by-layer (LbL) self-assembly method. It is well known that the charge heterogeneity of LL-37 can be a major setback for its LbL immobilization. Therefore, the surface charge of LL-37 was standardized via its complexation with heparin (Hep) to form protein-polyelectrolyte complexes (PPCsLL-37-Hep). The resulting PPCsLL-37-Hep were then used as new building blocks for LbL assembly with chitosan (Chi). As a matter of comparison, bare LL-37 was directly assembled with Hep into multilayers. The results show that the nano-architecture and -organization are influenced by the assembly strategy. The films built with PPCsLL-37-Hep are more viscoelastic and more hydrated than the bare LL-37-based multilayers. However, multilayers based on bare LL-37 incorporate more LL-37 than the PPCsLL-37-Hep-based multilayers because these latter would undergo a selfreorganization upon Chi adsorption. The LL-37 release profile from both LL-37- and PPCsLL-37-Hep-based multilayers is particularly interesting as the initial burst release is relatively moderate, followed by a prolonged and gradual release of AMP over an extended duration, which is useful for targeting both bacteria in the early stages of infection and opportunistic pathogens beyond this period. The thorough study of assembly conditions and the characterization of the obtained multilayers increased our understanding of LbL assembly of proteins. The developed coating demonstrates promising antibiofilm properties. This study highlights nevertheless the requirement of a multifaceted approach that leverages all available antimicrobial weapons to overcome biofilm-associated infections.
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Vranckx, C. (2024). Preventing infections on medical implants : integration of LL-37, an antimicrobial peptide, in multilayered coatings. https://hdl.handle.net/2078.5/235916