Antimicrobial Titanium Surface via Click-Immobilization of Peptide and Its in Vitro/Vivo Activity

Abstract

The use of antimicrobial peptides (AMPs)-functionalized titanium implants is an efficient method for preventing bacterial infection. However, the attachment of AMPs to the surface of titanium implants remains a challenge. In this study, a “clickable” titanium surface was developed by using a silane coupling agent with an alkynyl group. The antimicrobial titanium implant was then constructed through the reaction between the “clickable” surface and azido-AMPs (PEG-HHC36:N3-PEG12-KRWWKWWRR) via click chemistry of Cu­(I)-catalyzed azide–alkyne cycloaddition (CuAAC). Such an antimicrobial titanium implant, with an AMP density of 897.4 ± 67.3 ng/cm2 (2.5 ± 0.2 molecules per nm2) on the surface, exhibited good and stable antimicrobial activity, inhibited 90.2% of Staphylococcus aureus and 88.1% of Escherichia coli after 2.5 h of incubation, and even inhibited 69.5% of Staphylococcus aureus after 4 days of degradation. The CCK-8 assay indicated that the antimicrobial titanium implant exhibited negligible cytotoxicity to mouse bone mesenchymal stem cells. In vivo assay illustrated that this implant could kill 78.8% of Staphylococcus aureus after 7 days. This method has great potential for the preparation of antimicrobial titanium implants and the prevention of infections in the clinic.

Long acting anti-infection constructs on titanium

“…For this purpose, multilayers coatings containing chlorhexidine were prepared on the surfaces of titanium particles used as a model for actual implant devices as the procedure employed to deposit the coating is not affected by the size or shape of the substrate. In this context, the nanoparticles prepared and studied in this work were used as other commonly employed material models such as rods [38][39][40], disks [41] or wafers [20]; thus we did not envisage depositing the coated nanoparticles onto the surface of devices [42,43].…”

Host Defense Peptide-Mimicking Polymers and Polymeric-Brush-Tethered Host Defense Peptides: Recent Developments, Limitations, and Potential Success

“…In another study by Fang Z et al, polymer brushes with mono-and dual-peptide functionalized Ti rods implanted in a rabbit femur (bone) defect model exhibited excellent biocompatibility and antimicrobial activity [193]. Several other studies have reported in-vivo experiments [194][195][196][197][198] reinforcing the promise of using polymer-brush HDP-conjugate design to prepare functional biomaterial surfaces. In addition to their conjugation with standard polymer brushes, peptides with antimicrobial activity have also been integrated into or with other films/surfaces, such as protein-based films (i.e., self-assembled protein nanostructures) [199][200][201][202][203][204][205][206], silk surgical sutures [207,208], metal nanoparticles [209,210] and other solid interfaces, in order to provide biomaterials that can prevent and minimize the risks of bacterial infections.…”

Antimicrobial Surfaces for Applications on Confined Inhabited Space Stations

“…Furthermore, the PEG‐HHC36 peptide on a Ti surface with a silane coupling agent, [ 194 ] GZ3.27 lipopeptide on glass silicon or Ti surfaces via a thioether bond, [ 195 ] inverso‐CysHHC10 peptide with a polyethylene glycol (PEG) network on poly(ethylene terephthalate) (PET), [ 196 ] IG‐25 on fluoropolymers and M2‐DA on stainless steel [ 197 ] are also reported as peptide AM coatings. Collectively, these coatings demonstrate a broad range of AM activities and modes of action.…”