title: Lysophosphatidic acid-functionalised titanium as a superior surface for supporting human osteoblast (MG63) maturation.
abstract: Covalent modifications of titanium with small molecules known to promote human osteoblast maturation are especially attractive in developing superior biomaterials. An important step in securing competent bone formation at implant sites is promoting the formation of mature osteoblasts, either from committed pre-osteoblasts or from their mesenchymal progenitors. To this end our research has focussed on identifying molecules that enhance human osteoblast formation and maturation and to develop ways of covalently attaching these molecules to implant surfaces so that they are more likely to withstand the rigors of the implantation process whilst still retaining their bioactivity. Herein we report the novel production of lipid-functionalised titanium using lysophosphatidic acid or a related compound, (3S) 1-fluoro-3-hydroxy-4-butyl-1-phosphonate. Both lipids were especially effective at co-operating with calcitriol to promote human osteoblast maturation at these modified Ti surfaces in vitro. The novel findings presented offer enticing new developments towards the fabrication of next-generation implant devices with the potential to significantly enhance the osseointegration process and with it improvements in future prosthesis performance and longevity.
authors.affiliation: Musculoskeletal Research Unit, Avon Orthopaedic Centre, School of Clinical Sciences, University of Bristol, Westbury-on-Trym, BS10 5NB, UK. j.p.mansell@bris.ac.uk
authors.forename: Jason P
authors.initials: JP
authors.lastname: Mansell
authors.forename: Judith
authors.initials: J
authors.lastname: Brown
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Knapp
authors.forename: Charl F J
authors.initials: CF
authors.lastname: Faul
authors.forename: Ashley W
authors.initials: AW
authors.lastname: Blom
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008246:Lysophospholipids / Q000737:chemistry / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D063065:Organophosphonates / Q000737:chemistry / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D056951:Photoelectron Spectroscopy; D013499:Surface Properties; D013997:Time Factors; D014025:Titanium / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D050071:Bone Density Conservation Agents; D008246:Lysophospholipids; D063065:Organophosphonates; D014025:Titanium; D000469:Alkaline Phosphatase; D002117:Calcitriol; C032881:lysophosphatidic acid