Immobilised teicoplanin does not demonstrate antimicrobial activity against Staphylococcus aureus

Abstract: Antibacterial bone biomaterial coatings appeal to orthopaedics, dentistry and veterinary medicine. Achieving the successful, stable conjugation of suitable compounds to biomaterial surfaces is a major challenge. A pragmatic starting point is to make use of existing, approved antibiotics which are known to remain functional in a stationary, immobilised state. This includes the macrocyclic glycopeptide, teicoplanin, following the discovery, in the 1990’s, that it could be used as a chiral selector in chromatographic enantiomeric separations. Importantly teicoplanin works at the level of the bacterial cell wall making it a potential candidate for biomaterial functionalisations. We initially sought to functionalise titanium (Ti) with polydopamine and use this platform to capture teicoplanin, however we were unable to avoid the natural affinity of the antibiotic to the oxide surface of the metal. Whilst the interaction between teicoplanin and Ti was robust, we found that phosphate resulted in antibiotic loss. Before contemplating the covalent attachment of teicoplanin to Ti we examined whether a commercial teicoplanin stationary phase could kill staphylococci. Whilst this commercially available material could bind N-Acetyl-L-Lys-D-Ala-D-Ala it was unable to kill bacteria. We therefore strongly discourage attempts at covalently immobilising teicoplanin and/or other glycopeptide antibiotics in the pursuit of novel antibacterial bone biomaterials

Fluorophosphonate-functionalised titanium via a pre-adsorbed alkane phosphonic acid: a novel dual action surface finish for bone regenerative applications

© 2015, Springer Science+Business Media New York. Abstract: Enhancing vitamin D-induced human osteoblast (hOB) maturation at bone biomaterial surfaces is likely to improve prosthesis integration with resultant reductions in the need for revision arthroplasty consequent to aseptic loosening. Biomaterials that are less appealing to microorganisms implicated in implant failures through infection are also highly desirable. However, finding surfaces that enhance hOB maturation to active vitamin D yet deter bacteria remain elusive. In addressing this, we have sought to bio-functionalise titanium (Ti) with lysophosphatidic acid (LPA) and related, phosphatase-resistant, LPA analogues. The impetus for this follows our discovery that LPA co-operates with active vitamin D3 metabolites to secure hOB maturation in vitro including cells grown upon Ti. LPA has also been found, by others, to inhibit virulence factor production and biofilm formation of the human opportunistic pathogen Pseudomonas aeruginosa. Collectively, selected LPA species might offer potential dual-action surface finishes for contemporary bone biomaterials. In attaching a phosphatase-resistant LPA analogue to Ti we took advantage of the affinity of alkane phosphonic acids for TiO 2 . Herein, we provide evidence for the facile development of a dual-action Ti surface for potential orthopaedic and dental applications. Successful conjugation of an LPA analogue (3S)1-fluoro-3-hydroxy-4-(oleoyloxy)butyl-1-phosphonate (FHBP) to the Ti surface was supported through physiochemical characterisation using x-ray photoelectron spectroscopy and secondary ion mass spectrometry. hOB maturation to active vitamin D3 was enhanced for cells grown on FHBP-Ti whilst these same surfaces exhibited clear antiadherent properties towards a clinical isolate of Staphylococcus aureus. Graphical Abstract: [Figure not available: see fulltext.