Mitigation of Peri-implantitis by Rational Design of Bifunctional Peptides with Antimicrobial Properties

Abstract

The integration of molecular and cell biology with materials science has led to strategies to improve the interface between dental implants with the surrounding soft and hard tissues in order to replace missing teeth and restore mastication. More than 3 million implants have been placed in the US alone and this number is rising by 500,000/year. Peri-implantitis, an inflammatory response to oral pathogens growing on the implant surface threatens to reduce service life leading to eventual implant failure, and such an outcome will have adverse impact on public health and create significant health care costs. Here we report a predictive approach to peptide design, which enabled us to engineer a bifunctional peptide to combat bacterial colonization and biofilm formation, reducing the adverse host inflammatory immune response that destroys the tissue surrounding implants and shortens their lifespans. This bifunctional peptide contains a titaniumbinding domain that recognizes and binds with high affinity to titanium implant surfaces, fused through a rigid spacer domain with an antimicrobial domain. By varying the antimicrobial peptide domain, we were able to predict the properties of the resulting bifunctional peptides in their entirety by analyzing the sequence-structure-function relationship. These bifunctional peptides achieve: 1) nearly 100% surface coverage within minutes, a timeframe suitable for their clinical application to existing implants; 2) nearly 100% binding to a titanium surface even in the presence of contaminating serum protein; 3) durability to brushing with a commercially available electric toothbrush; and 4) retention of antimicrobial activity on the implant surface following bacterial challenge. A bifunctional peptide film can be applied to both new implants and/or repeatedly applied to previously placed implants to control bacterial colonization mitigating peri-implant disease that threatens dental implant longevity.

Next‐generation Antimicrobial Peptides (AMPs) incorporated nanofibre wound dressings

“…The M2 peptide model shows mostly α‐helix secondary structure with a positive charge; however, the hydrophobic ratio is lower than the hydrophobic ratio of AMP2. This could support AMP2 functioning more effectively as an AMP compared to M2 (Wisdom et al, 2020).…”

“…however, the hydrophobic ratio is lower than the hydrophobic ratio of AMP2. This could support AMP2 functioning more effectively as an AMP compared to M2 (Wisdom et al, 2020). Figure 7b shows a significant reduction in bacterial growth with PEO-AMP2, which shows that there is a stronger antibacterial effect on S. epidermidis compared with PEO-M2 nanofibres.…”

Surface Immobilization Chemistry of a Laminin-Derived Peptide Affects Keratinocyte Activity

“…Previous research compared a classic amino acid spacer (GGG) and a novel spacer (GSGGG) with a “backbone bend” to separate an antimicrobial peptide domain from the surface. This novel GSGGG spacer showed enhanced antimicrobial activity compared to the classic spacer we used here [ 57 , 58 ]. Other work has compared a rigid spacer [(EAAAK) 4 ] against a flexible spacer [(GGGGS) 4 ]; the flexible spacer design showed more effective eukaryotic cell signaling but less effective antimicrobial activity [ 36 , 59 ].…”

Harnessing biomolecules for bioinspired dental biomaterials

“…[376][377][378][379] An important aspect of chimeric peptides is their properties can be improved using computational modeling and predictive tools. [380][381][382] Peptides are particularly attractive for this purpose because of their ease of manufacture. 383 A relatively common way to generate such biomolecules is to pair a bioactive domain (such as growth factor, signaling molecule, etc.)…”