Directed Assembly of PEGylated-Peptide Coatings for Infection-Resistant Titanium Metal

Abstract

Appropriate surface chemistry between a material and its surrounding biological environment is crucial to the eventual integration and performance of any implant, whether metal, plastic, or ceramic. A robust peptide-based coating technology capable of easily modifying the surface of titanium (Ti) metal through noncovalent binding is described. A short peptide possessing affinity for Ti was identified using a phage display screening process and subjected to an amino acid substitution exercise using solid-phase chemical synthesis. Through these studies, the HKH tripeptide motif was elucidated as an important contributor to Ti binding within the Ti-binding peptide. This peptide spontaneously and selectively adsorbs onto a Ti surface from dilute aqueous solution with submicromolar binding affinities as determined by ELISA and quartz crystal microbalance with dissipation monitoring (QCM-D), through a process largely dominated by electrostatic interactions. Atomic force microscopy (AFM) reveals a densely packed peptide adlayer with an average height of approximately 0.5 nm. Subsequently, a PEGylated analogue of the peptide was shown to rapidly coat Ti to afford a nonfouling surface that efficiently blocked the adsorption of fibronectin and significantly reduced the extent of Staphylococcus aureus attachment and biofilm formation in vitro. These PEGylated-peptide coatings show promise in terms of resolving two major hurdles common to implanted metals: (i) nonspecific protein adsorption and (ii) bacterial colonization. At the same time, the facile one-step modification process will facilitate the point-of-care application of these coatings in the surgical suite.

Biofilm-Related Infections: Bridging the Gap between Clinical Management and Fundamental Aspects of Recalcitrance toward Antibiotics

“…Thus, different attempts have been made to reduce not only microbial adhesion but also the deposition of host components or the occurrence of thrombosis. To do so, a peptide-based coating technology was proposed to modify the surface of Ti metal through noncovalent binding (258). In that study, a peptide (SHKHGGHKHGSSGK) possessing affinity for Ti was identified and coated with a pegylated analogue that efficiently blocked adsorption of fibronectin and S. aureus adhesion (258).…”

“…To do so, a peptide-based coating technology was proposed to modify the surface of Ti metal through noncovalent binding (258). In that study, a peptide (SHKHGGHKHGSSGK) possessing affinity for Ti was identified and coated with a pegylated analogue that efficiently blocked adsorption of fibronectin and S. aureus adhesion (258). Another group used lysozyme immobilized on polyethylene glycol monomethacrylate (PEGMA) to coat stainless steel surfaces and demonstrated that bacterial adhesion and albumin adsorption were reduced (259).…”

New Strategies in the Development of Antimicrobial Coatings: The Example of Increasing Usage of Silver and Silver Nanoparticles

“…The peptides contained several HKH motifs that show specific binding with high affinity to titanium surfaces. The resulting surfaces showed reduced protein and bacterial adhesion [41].…”

Molecular engineering of an orthopaedic implant: from bench to bedside

“…One approach to overcoming the problems mentioned above is to covalently bond a biocidal molecule to the surface of an implant. For titanium, linkages reported include diphosphonic acid (Danahy et al, 2004), plasma animation (Puleo et al, 2002), silanisation (Wojcik and Puleo, 1997;Antoci et al, 2007d;Sechi et al, 2007), photopolymerisation (Lawson et al, 2007), p-nitrophenyl chloroformate treatment (Mikulec and Puleo, 1996) and PEGylation (Khoo et al, 2009). This type of surface would prevent bacterial attachment and therefore block biofilm formation.…”