title: Fluorophosphonate-functionalised titanium via a pre-adsorbed alkane phosphonic acid: a novel dual action surface finish for bone regenerative applications.
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 TiO2. 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.
authors.affiliation: School of Dentistry, Cardiff University, Cardiff, CF14 4XY, UK.
authors.forename: Wayne Nishio
authors.initials: WN
authors.lastname: Ayre
authors.affiliation: Interface Analysis Centre, School of Physics, University of Bristol, Bristol, BS8 1TL, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Scott
authors.affiliation: Interface Analysis Centre, School of Physics, University of Bristol, Bristol, BS8 1TL, UK.
authors.forename: Keith
authors.initials: K
authors.lastname: Hallam
authors.affiliation: Musculoskeletal Research Unit, University of Bristol, Southmead Hospital, Bristol, BS10 5NB, UK.
authors.forename: Ashley W
authors.initials: AW
authors.lastname: Blom
authors.affiliation: University of Brighton, Mithras House, Brighton, BN2 4AT, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Denyer
authors.affiliation: CATIM, University of the West of England, Frenchay Campus, Bristol, BS16 1QY, UK.
authors.forename: Heather K
authors.initials: HK
authors.lastname: Bone
authors.affiliation: Department of Biological, Biomedical & Analytical Sciences, University of the West of England, Coldharbour Lane, Bristol, BS16 1QY, UK. jason.mansell@uwe.ac.uk.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Mansell
mesh_terms: D000473:Alkanes / Q000138:chemical synthesis / Q000737:chemistry; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D057219:Biofouling / Q000517:prevention & control; D001861:Bone Regeneration; D002454:Cell Differentiation; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D005459:Fluorides / Q000737:chemistry*; D006801:Humans; D007720:Knee Prosthesis / Q000382:microbiology; D008246:Lysophospholipids / Q000737:chemistry; D008422:Materials Testing; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology; D010757:Phosphorous Acids / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000254:growth & development / Q000302:isolation & purification; D013499:Surface Properties; D023822:Tissue Engineering / Q000379:methods; D014025:Titanium / Q000737:chemistry*
chemical_list: D000473:Alkanes; D020099:Coated Materials, Biocompatible; D008246:Lysophospholipids; D010757:Phosphorous Acids; C570063:phosphonic acid; D014025:Titanium; C032881:lysophosphatidic acid; D005459:Fluorides