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

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 ∼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 <i>Staphylococcus aureus</i> attachment and biofilm formation <i>in vitro</i>. 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.