Biological and immunotoxicity evaluation of antimicrobial peptide-loaded coatings using a layer-by-layer process on titanium

Abstract

The prevention and control of peri-implantitis is a challenge in dental implant surgery. Dental implants with sustained antimicrobial coating are an ideal way of preventing peri-implantitis. This study reports development of a non- immunotoxicity multilayered coating on a titanium surface that had sustained antimicrobial activity and limited early biofilm formation. In this study, the broad spectrum AMP, Tet213, was linked to collagen IV through sulfo-SMPB and has been renamed as AMPCol. The multilayer AMPCol coatings were assembled on smooth titanium surfaces using a LBL technique. Using XPS, AFM, contact angle analysis, and QCM, layer-by-layer accumulation of coating thickness was measured and increased surface wetting compared to controls was confirmed. Non-cytotoxicity to HaCaT and low erythrocyte hemolysis by the AMPCol coatings was observed. In vivo immunotoxicity assays showed IP administration of AMPCol did not effect serum immunoglobulin levels. This coating with controlled release of AMP decreased the growth of both a Gram-positive aerobe (Staphylococcus aureus) and a Gram-negative anaerobe (Porphyromonas gingivalis) up to one month. Early S. aureus biofilm formation was inhibited by the coating. The excellent long-term sustained antimicrobial activity of this multilayer coating is a potential method for preventing peri-implantitis through coated on the neck of implants before surgery.

Engineering a sprayable and elastic hydrogel adhesive with antimicrobial properties for wound healing

“…In recent years, significant efforts have been made to develop macromolecular antimicrobial agents that are impervious to antibiotic resistance, and can be used in the context of chronic wound treatment [62]. AMPs are comprised of short sequences of cationic amino acids, which have been shown to possess broadspectrum bactericidal activity against G(þ/À) bacteria [63]. AMPs bind to the negatively charged outer leaflet of bacterial cell membranes, which leads to changes in bacterial surface electrostatics, actuation upon cytoplasmic targets, increased membrane permeabilization, and ultimately, cell lysis [6,64].…”

A comparative analysis of antibacterial properties and inflammatory responses for the KR-12 peptide on titanium and PEGylated titanium surfaces

“…[7][8][9][10][11][12] Various approaches based on the physical or chemical immobilisation of AMPs have been developed to generate antibacterial surfaces, including covalent immobilisation, layer-by-layer techniques, and local release on the Ti surface. [13][14][15] The local controlled release of AMPs has certain disadvantages, including short effective times, large dose requirements, and the development of bacterial resistance when small doses are used. Covalent immobilisation of AMPs on Ti surfaces is an effective approach to mitigate Ti implantassociated infections with long-term stability and low toxicity.…”

Modification of the surface of titanium with multifunctional chimeric peptides to prevent biofilm formation via inhibition of initial colonizers

“…In order to avoid biofilmassociated infections, various strategies have been developed to improve the antimicrobial properties of biomaterial surfaces including loading with antibiotics, 31 covalent attachment of AMPs, [14][15][16] and polymer-based surface modification. [32][33][34][35] Although these methods can inhibit bacterial attachment, the procedure is tedious and has a limited efficacy in practice. To overcome these limitations and combat the issues of antibiotic resistance and toxicity, a Ti-binding protein was used to connect the multifunctional chimeric peptides with the Ti surface.…”