Abstract
In western countries, one patient on twenty will develop a nosocomial infection during his hospitalization at health care facilities. Classical antibiotics being less and less effective, this phenomenon is expanding year after year. Prevention of bacteria colonization of implantable medical devices constitutes a major medical and financial issue. In this study, we developed an antibacterial coating based on self-assembled Fmoc-tripeptide. Fmoc-FFpY peptides (F: phenylalanine; Y: tyrosine; p: PO42–) are dephosphorylated enzymatically into Fmoc-FFY by action of alkaline phosphatase functionalized silica nanoparticles (NPs@AP), previously deposited on a surface. Fmoc-FFY peptides then self-assemble through π–π stacking interactions, hydrogen bonds and hydrophobic interactions adopting β-sheets secondary structures. The obtained hydrogel coatings show fibrillary structures observed by cryo-scanning electron microscopy with a thickness of few micrometers. At low concentration (≤0.5 mg.mL–1), self-assembled Fmoc-FFY has a superior antibacterial activity than Fmoc-FFpY peptide in solution. After 24 h of incubation, Fmoc-FFY hydrogel coatings fully inhibit the development of Gram-positive Staphylococcus aureus (S. aureus). The antibacterial effect is maintained on an in vitro model of repetitive infection in the case of S. aureus. This coating could serve in infections were Gram positive bacteria are prevalent, e.g., intravascular catheter infections. This work gives new insights toward the design of an alternative antimicrobial coating.
Highlights
Biomedical implants, i.e., prosthetics, catheters or intraocular lenses, are indispensable in medicine and gain increasing attention over the years (Lombardi et al, 2019)
We introduced the use of non-self-assembling Fmoc-FFpY peptide (Y: tyrosine; p: PO42−), which is transformed into the hydrogelator Fmoc-FFY by alkaline phosphatase (AP)
When NPs@AP suspension is put in contact with the polyelectrolyte multilayer (PEM) precursor film, a high increase of the normalized frequency shift is observed by Quartz Crystal Microbalance With Dissipation Monitoring (QCM-D) reaching about 700 Hz after the rinsing steps (Figure 1A)
Summary
Biomedical implants, i.e., prosthetics, catheters or intraocular lenses, are indispensable in medicine and gain increasing attention over the years (Lombardi et al, 2019). Biofilm formation contributes to the resistance to antibiotic treatments, it protects the bacterial colonies from host defense systems and bactericidal agents (Kaplan, 2011). This leads to the chemotherapeutic failure which often results in an increase of the resistance mechanism adopted by many bacterial strains, those involving S. aureus (Darouiche, 2004). In this scenario, the development of antimicrobial coatings to protect against such infections has become a major field of scientific and technological research (Séon et al, 2015). Self-assembly of peptides, with a sequenced-defined chemical structure, can give hydrogels with a desired functionality which becomes increasingly attractive in the development of therapeutics materials (Makam and Gazit, 2018; Criado-Gonzalez et al, 2020a)
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