title: Osteoblast lineage cells can discriminate microscale topographic features on titanium-aluminum-vanadium surfaces.
abstract: Titanium (Ti) and Ti alloys are used in orthopaedic/spine applications where biological implant fixation, or osseointegration, is required for long-term stability. These implants employ macro-scale features to provide mechanical stability until arthrodesis, features that are too large to influence healing at the cellular level. Micron-scale rough Ti alloy (Ti-6Al-4V) increases osteoblastic differentiation and osteogenic factor production in vitro and increases in vivo bone formation; however, effects of overall topography, including sub-micron scale and nanoscale features, on osteoblast lineage cells are less well appreciated. To address this, Ti6Al4V surfaces with macro/micro/nano-textures were generated using sand blasting and acid etching that had comparable average roughness values but differed in other roughness parameters (total roughness, profile roughness, maximum peak height, maximum valley depth, root-mean-squared roughness, kurtosis, skewness) (#5, #9, and #12). Human mesenchymal stem cells (HMSCs) and normal human osteoblasts (NHOst) were cultured for 7 days on the substrates and then analyzed for alkaline phosphatase activity and osteocalcin content, production of osteogenic local factors, and integrin subunit expression. All three surfaces supported osteoblastic differentiation of HMSCs and further maturation of NHOst cells, but the greatest response was seen on the #9 substrate, which had the lowest skewness and kurtosis. The #9 surface also induced highest expression of α2 and β1 integrin mRNA. HMSCs produced highest levels of ITGAV on #9, suggesting this integrin may play a role for early lineage cells. These results indicate that osteoblast lineage cells are sensitive to specific micro/nanostructures, even when overall macro roughness is comparable and suggest that skewness and kurtosis are important variables.
authors.affiliation: Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Rene
authors.initials: R
authors.lastname: Olivares-Navarrete
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Hyzy
authors.forename: Mark E
authors.initials: ME
authors.lastname: Berg
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Schneider
authors.forename: Kelly
authors.initials: K
authors.lastname: Hotchkiss
authors.forename: Zvi
authors.initials: Z
authors.lastname: Schwartz
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Boyan
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000497:Alloys; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D053244:Osteoprotegerin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013499:Surface Properties; D014025:Titanium; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000497:Alloys; C525718:BMP2 protein, human; C525809:BMP4 protein, human; D001672:Biocompatible Materials; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D016023:Integrins; D053244:Osteoprotegerin; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D015675:Osteocalcin; C031462:titanium alloy (TiAl6V4); D005346:Fibroblast Growth Factors; D004247:DNA; D014025:Titanium; D000469:Alkaline Phosphatase