Chimeric Peptides as Implant Functionalization Agents for Titanium Alloy Implants with Antimicrobial Properties

Abstract

Implant-associated infections can have severe effects on the longevity of implant devices and they also represent a major cause of implant failures. Treating these infections associated with implants by antibiotics is not always an effective strategy due to poor penetration rates of antibiotics into biofilms. Additionally, emerging antibiotic resistance poses serious concerns. There is an urge to develop effective antibacterial surfaces that prevent bacterial adhesion and proliferation. A novel class of bacterial therapeutic agents, known as antimicrobial peptides (AMP’s), are receiving increasing attention as an unconventional option to treat septic infection, partly due to their capacity to stimulate innate immune responses and for the difficulty of microorganisms to develop resistance towards them. While host- and bacterial- cells compete in determining the ultimate fate of the implant, functionalization of implant surfaces with antimicrobial peptides can shift the balance and prevent implant infections. In the present study, we developed a novel chimeric peptide to functionalize the implant material surface. The chimeric peptide simultaneously presents two functionalities, with one domain binding to a titanium alloy implant surface through a titanium-binding domain while the other domain displays an antimicrobial property. This approach gains strength through control over the bio-material interfaces, a property built upon molecular recognition and self-assembly through a titanium alloy binding domain in the chimeric peptide. The efficiency of chimeric peptide both in-solution and absorbed onto titanium alloy surface was evaluated in vitro against three common human host infectious bacteria, S. mutans, S. epidermidis, and E. coli. In biological interactions such as occurs on implants, it is the surface and the interface that dictate the ultimate outcome. Controlling the implant surface by creating an interface composed chimeric peptides may therefore open up new possibilities to cover the implant site and tailor it to a desirable bioactivity.

Antimicrobial dental implant functionalization strategies —A systematic review

“…Furthermore, AMP surfaces displayed antimicrobial activity under dynamic growth conditions against S. gordonii 156) and under static growth conditions against Streptococcus mutans, Staphylococcus epidermidis and Escherichia coli 159) . This passive antimicrobial coating resisted hydrolytic and mechanical challenges and exhibited no significant release of peptides from the modified titanium surface.…”

Controlling the Biomimetic Implant Interface: Modulating Antimicrobial Activity by Spacer Design

“…In our previous studies, we demonstrated that AMPs can be immobilized on titanium implant surfaces through the engineering of chimeric peptides that use molecular recognition to attach and self-assemble on the implant surface as a novel biomolecular-coating. 24–26 A chimeric peptide is a bifunctional single-chain relatively short peptide when compared to biological proteins, and it joins two functional domains through an engineered spacer. The functional domain joined to the AMP for immobilization on implant surface is a peptide that is identified using combinatorial biology based molecular libraries, i.e., phage and cell surface display libraries.…”

“…27,28 Previous work has identified several titanium binding peptides (TiBP) that assemble onto the titanium surface with high affinity appropriate for the surface of titanium and titanium alloy-based implants. 24,25 Peptide-based self-immobilization strategies therefore offer an opportunity to overcome the limitations and challenges associated with covalent immobilization of antibacterial agents on implant surfaces.…”

Cecropin B loaded TiO2 nanotubes coated with hyaluronidase sensitive multilayers for reducing bacterial adhesion

“…To avoid or reduce such undesirable consequences, some antibacterial agents (e.g., antimicrobial peptides, antibacterial ions, Ag nanoparticles etc.) were used for the fabrication of clinical antibacterial implants [6][7][8][9][10]. Although the sustained release of these substances could inhibit bacteria adhesion while ensuring the biosafety of implants against surrounding cells/tissues, the early stage (4-6 h) bacteria inhibition is not in well control to some extent.…”