Staphylococcus aureus resistance on titanium coated with multivalent PEGylated-peptides

Abstract

Bacterial infections can have adverse effects on the efficacy, lifetime and safety of an implanted device and are the second most commonly attributed cause of orthopedic implant failure. We have previously shown the assembly of PEGylated titanium-binding peptides (TBPs) on Ti to obtain a bacteriophobic surface coating that can effectively resist protein adsorption and Staphylococcus aureus (S. aureus) adhesion. In the present study, we examine the effect of multiple TBP repeats on coating performance in vitro. Mono, di, and tetravalent peptides were synthesized and assessed for binding affinity and serum stability. PEGylated analogs were prepared and evaluated for their effect on S. aureus attachment and biofilm formation. Coating performance improved with the number of TBP repeats, with the tetravalent coating, TBP4–PEG, showing the best performance in all assays. In particular, TBP4–PEG forms a serum-resistant surface coating capable of preventing S. aureus colonization and subsequent biofilm formation. These results further support the role that multivalency can play in the development of improved surface coatings with enhanced stabilities and efficacy for in vivo clinical use.

Liquid-infused structured surfaces with exceptional anti-biofouling performance

“…The SLIPS liquid in our setup is infiltrated into a porous polytetrafluoroethylene (PTFE) substrate (40)(41)(42)(43) or microstructured fluoro-silanized Si wafer and presented as a smooth liquid-liquid interface to bacteria. Through rigorous quantification, we demonstrate that our SLIPS platform prevents up to 96-99% of common bacterial biofilms from attaching over at least a 7-d period in a low flow environment, a 35 times greater advance over best-case-scenario, state-of-the-art surface chemistry treatments based on PEGylation (44). This result extends across bacterial species, including the clinical pathogens P. aeruginosa, S. aureus, and E. coli.…”

“…Scale bar ¼ 2 cm. (F) Comparison of biofilm attachment to our SLIPS substrate after 7 d and to a PEGylated substrate after 5 h, as reported in (44). Even assuming a best-case scenario in which its 5 h PEG performance can be maintained at 7 d without desorption or masking of surface chemistry, the 0.4% relative attachment to SLIPS represents a >30 times improvement.…”

Covalent Immobilization of Enoxacin onto Titanium Implant Surfaces for Inhibiting Multiple Bacterial Species Infection and In Vivo Methicillin-Resistant Staphylococcus aureus Infection Prophylaxis

“…A spacer is always needed prior to the covalent attachment of antibiotics to a Ti surface (5) and serves as a bridge that links antibacterial agents to the implant surface, making the orientation of antibacterial agents more flexible. PEG has been widely used as a spacer because of its nontoxicity and its functional group, which may be easily modified to link to various bioactive molecules and antibacterial agents (35). In the current study, the PEG molecules could extend enoxacin away from the Ti surface, allowing enoxacin to enter the bacterial cell wall and bind to the bacterium's DNA gyrase and topoisomerase IV.…”

Multifunctional biomaterial coatings: synthetic challenges and biological activity

“…This could be applied to study the anchor strength of the conjugate, listed in Table 1, line e., consisting of a polystyrene-binding peptide and the integrin-ligand RRETAWA (Khoo et al, 2010;Meyers et al, 2011).…”

“…Surface binding peptides can be replaced by salts or proteins or degraded under physiological conditions, thus it is important to study the binding stability of the peptide (Micksch et al, 2014). The advantage of peptide-based approaches is the easy introduction of bioactive motifs to the anchor molecule (Khoo et al, 2010). Electrostatic interactions are mostly applied between a negatively charged surface such as TiO 2 and positively charged amino acids (aa).…”