Engineered Chimeric Peptides as Antimicrobial Surface Coating Agents toward Infection-Free Implants

Abstract

Prevention of bacterial colonization and consequent biofilm formation remains a major challenge in implantable medical devices. Implant-associated infections are not only a major cause of implant failures but also their conventional treatment with antibiotics brings further complications due to the escalation in multidrug resistance to a variety of bacterial species. Owing to their unique properties, antimicrobial peptides (AMPs) have gained significant attention as effective agents to combat colonization of microorganisms. These peptides have been shown to exhibit a wide spectrum of activities with specificity to a target cell while having a low tendency for developing bacterial resistance. Engineering biomaterial surfaces that feature AMP properties, therefore, offer a promising approach to prevent implant infections. Here, we engineered a chimeric peptide with bifunctionality that both forms a robust solid-surface coating while presenting antimicrobial property. The individual domains of the chimeric peptides were evaluated for their solid-binding kinetics to titanium substrate as well as for their antimicrobial properties in solution. The antimicrobial efficacy of the chimeric peptide on the implant material was evaluated in vitro against infection by a variety of bacteria, including Streptococcus mutans, Staphylococcus. epidermidis, and Escherichia coli, which are commonly found in oral and orthopedic implant related surgeries. Our results demonstrate significant improvement in reducing bacterial colonization onto titanium surfaces below the detectable limit. Engineered chimeric peptides with freely displayed antimicrobial domains could be a potential solution for developing infection-free surfaces by engineering implant interfaces with highly reduced bacterial colonization property.

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

“…The spectrum for the chimeric peptide with Spacer5 indicates a greater preference for right-circularly polarized light absorbance compared to the previously published spectrum for Spacer3, indicating that the predominance of α -helix secondary structure present in TiBP-Spacer3-AMP is not preserved through the newly designed Spacer5. 26 The CD structural prediction results are consistent with the computationally predicted secondary structure analysis, indicating that a majority of the secondary structure of TiBP-Spacer5-AMP is β -sheet or random coil. Moreover, both the CAPITO and Raussens method assigns 86% and 55% secondary structure to irregular or random coil features, for TiBP-Spacer5-AMP, respectively.…”

“…The feature designated by the arrow indicates a greater preference for right-circularly polarized light absorbance compared to the previously published spectrum for chimeric peptide with Spacer3. 26 The CAPITO and Raussens methods indicates a predominance of irregular and random coil features in the spectrum consistent with what is observed in the computationally generated secondary structure for TiBP-Spacer5-AMP shown in Fig. 1(b).…”

“…40,41 Data from a similar chimeric peptide with identical functional domains, but a shorter spacer sequence (TiBP-Spacer3-AMP) and the AMP peptide alone were used to evaluate the effect of the new engineered spacer design. 24–26 Table 1 contains the sequences and physical chemical properties for each chimeric peptide and their functional domains. Despite the physical chemical similarity to one another, we observed improved antimicrobial activity with the altered amino acid composition designed into the longer spacer called Spacer5.…”

“…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.…”

Biosilver nanoparticle interface offers improved cell viability

“…Over the past decade, inorganic binding peptides (BPs) have been proven as robust surface functionalisation agents on different metal and metal oxide surfaces. 32,52–54 In the authors’ previous work, a multifunctional fusion protein was designed, which included a silver BP, identified using phage display technology, coupled to a green fluorescent protein (GFP). 34 It was demonstrated that the silver BP tag directs the fusion protein to self-immobilise selectively onto silver NP arrays on ferroelectric materials.…”