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

Abstract

Surgical site infection is a common cause of post-operative morbidity, often leading to implant loosening, ultimately requiring revision surgery, increased costs and worse surgical outcomes. Since implant failure starts at the implant surface, creating and controlling the bio-material interface will play a critical role in reducing infection while improving host cell-to-implant interaction. Here, we engineered a biomimetic interface based upon a chimeric peptide that incorporates a titanium binding peptide (TiBP) with an antimicrobial peptide (AMP) into a single molecule to direct binding to the implant surface and deliver an antimicrobial activity against S. mutans and S. epidermidis, two bacteria which are linked with clinical implant infections. To optimize antimicrobial activity, we investigated the design of the spacer domain separating the two functional domains of the chimeric peptide. Lengthening and changing the amino acid composition of the spacer resulted in an improvement of minimum inhibitory concentration by a three-fold against S. mutans. Surfaces coated with the chimeric peptide reduced dramatically the number of bacteria, with up to a nine-fold reduction for S. mutans and a 48-fold reduction for S. epidermidis. Ab initio predictions of antimicrobial activity based on structural features were confirmed. Host cell attachment and viability at the biomimetic interface were also improved compared to the untreated implant surface. Biomimetic interfaces formed with this chimeric peptide offer interminable potential by coupling antimicrobial and improved host cell responses to implantable titanium materials, and this peptide based approach can be extended to various biomaterials surfaces.

Repeatedly Applied Peptide Film Kills Bacteria on Dental Implants

“… 23 , 25 , 41 Similarly, we have previously established the importance of engineering the design of the spacer to optimize the function of the antimicrobial peptide domain in the bifunctional peptide construct. 41 The spacer serves as a link between the two functional domains and is designed to preserve the secondary structure of each individual domain, a parameter that is tightly linked to antimicrobial function. Here, a novel AMP domain obtained from literature was linked to the TiBP through a “spacer5” to create a bifunctional peptide, as previously studied.…”

“…Here, a novel AMP domain obtained from literature was linked to the TiBP through a “spacer5” to create a bifunctional peptide, as previously studied. 41 The antimicrobial peptide (AMP domain) and the bifunctional peptide was selected through a rational design process based on previously determined antimicrobial “rules”. 23 The minimum inhibitory concentration for the TiBP-spacer5-AMP bifunctional peptide was established at 64 iM for an ATCC line of S. mutans ( Fig.…”

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 ].…”

Threats to adhesive/dentin interfacial integrity and next generation bio‐enabled multifunctional adhesives

“…With the emergence of bacterial resistance, antimicrobial peptides, which are naturally integrated in the oral fluids, are getting high attention as a promising solution to prevent bacterial infections at the a/d interface . Building upon the strength of our research team in antimicrobial peptide design and application at biomaterial interfaces, we modified an antimicrobial peptide sequence to integrate into a dental adhesive system. The antimicrobial peptide coupled adhesive formulations demonstrated significant antimicrobial activity with the resin, when applied to the discs .…”