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

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 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 per 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 an 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 life spans. This bifunctional peptide contains a titanium-binding 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 time frame 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 or repeatedly applied to previously placed implants to control bacterial colonization mitigating peri-implant disease that threatens dental implant longevity.