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Vol. 178, No. 1, 2004
Issue release date: 2004

Cellular Reactions of Osteoblasts to Micron- and Submicron-Scale Porous Structures of Titanium Surfaces

Zhu X. · Chen J. · Scheideler L. · Altebaeumer T. · Geis-Gerstorfer J. · Kern D.
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Osteoblast reactions to topographic structures of titanium play a key role in host tissue responses and the final osseointegration. Since it is difficult to fabricate micro- and nano-scale structures on titanium surfaces, little is known about the mechanism whereby the topography of titanium surfaces exerts its effects on cell behavior at the cellular level. In the present study, the titanium surface was structured in micron- and submicron-scale ranges by anodic oxidation in either 0.2 M H3PO4 or 0.03 M calcium glycerophosphate with 0.15 calcium acetate. The average dimensions of pores in the structured surface were about 0.5 and 2 µm in diameter, with roughness averaging at 0.2 and 0.4 µm, respectively. Enhanced attachment of cells (SaOS-2) was shown on micron- and submicron-scale structures. Initial cell reactions to different titanium surfaces, e.g. the development of the actin-containing structures, are determined by the different morphology of the surfaces. It is demonstrated that on either micron- or submicron-structured surfaces, many well-developed filopodia were observed to be primary adhesion structures in cell-substrate interactions, and some of them entered pores using their distinct tips or points along their length for initial attachment. Therefore, porous structures at either micro- or submicrometre scale supply positive guidance cues for anchorage-dependent cells to attach, leading to enhanced cell attachment. In contrast, the cells attached to a smooth titanium surface by focal contacts around their periphery as predominant adhesion structures, since repulsive signals from the environment led to retraction of the filopodia back to the cell bodies. These cells showed well-organized stress fibres, which exert tension across the cell body, resulting in flattened cells.

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  1. Adams, J.C. (1997) Characterization of cell-matrix adhesion requirements for the formation of fascin microspikes. Mol Biol Cell 8: 2345–2363.
  2. Adams, J.C. (2001) Cell-matrix contact structures. Cell Mol Life Sci 58: 371–392.
  3. Albrecht-Buehler, G. (1976) Filopodia of spreading 3T3 cells: do they have a substrate-exploring function? J Cell Biol 69: 275–286.
  4. Anselme, K., M. Bigerelle, B. Noel, E. Dufresne, D. Judas, A. Iost, P. Hardouin (2000) Qualitative and quantitative study of human osteoblast adhesion on materials with various surface roughnesses. J Biomed Mater Res 49: 155–166.
  5. Anselme, K., M. Bigerelle, B. Noel, A. Iost, P. Hardouin (2002) Effect of grooved titanium substrate on human osteoblastic cell growth. J Biomed Mater Res 60: 529–540.
  6. Arregui, C.O., S. Caronetto, L. McKerracher (1994) Characterization of neural cell adhesion sites: point contacts are the sites of interaction between integrins and the cytoskeleton in PC 12 cells. J Neurosci 14: 6967–6977.
  7. Bershadsky, A.D., I.S. Tint, A.A. Neyfakh Jr., J.M. Vasiliev (1985) Focal contacts of normal and RSV-transformed quail cells. Hypothesis of the transformation-induced deficient maturation of focal contacts. Exp Cell Res 158: 433–444.
  8. Boyan, B.D., C.H. Lohmann, D.D. Dean, V.L. Sylvia, D.L. Cochran, Z. Schwartz (2001) Mechanisms involved in osteoblast response to implant surface morphology. Annu Rev Mater Res 31: 357–371.
  9. Brittain, S., K. Paul, X. Zhao, G. Whitesides (May 1998) Soft lithography and microfabrication. Phys World, pp 31–36.
  10. Brunette, D.M. (1986) Fibroblasts on micromachined substrata orient hierarchically to grooves of different dimensions. Exp Cell Res 164: 11–26.
  11. Brunette, D.M. (1988) The effects of implant surface topography on the behavior of cells. Int J Oral Maxillofac Implants 3: 231–246.
  12. Chen, P.L., C.T. Kuo (2003) Self-organized titanium oxide nanodot arrays by electrochemical anodization. Appl Phys Lett 82: 2796–2798.
  13. Chou, L., J. Firth, V. Uitto, D.M. Brunette (1995) Substrate surface topography alters cell shape and regulates fibronectin mRNA level, mRNA stability, secretion and assembly in human fibroblasts. J Cell Sci 108: 1563–1573.
  14. Cooper, L.F. (2000) A role for surface topography in creating and maintaining bone at titanium endosseous implants. J Prosthet Dent 84: 522–534.
  15. Curtis, A.S.G. (2001) Cell reactions with biomaterials: the microscopies. Eur Cell Mater 1: 59–65.
  16. Curtis, A.S.G, P. Clark (1990) The effect of topographic and mechanical properties of materials on cell behaviour. Crit Rev Biocompat 5: 343–362.
  17. Curtis, A.S.G., C.D.W. Wilkinson (1997) Topographical control of cells. Biomaterials 18: 1573–1583.
  18. Dunn, G.A., A.F. Brown (1986) Alignment of fibroblasts on grooved surfaces described by a simple geometric transformation. J Cell Sci 83: 313–340.
  19. Ferri, Y., O. Piotrowski, P.F. Chauvy, C. Madore, D. Landolt (2001) Two-level electrochemical micromachining of titanium for device fabrication. J Micromech Microeng 11: 522–527.
  20. Friedl, P., E.B. Bröcke (2000) The biology of cell locomotion within three-dimensional extracellular matrix. Cell Mol Life Sci 57: 41–67.
  21. Gumbiner, B.M. (1996) Cell adhesion: the molecular basis of tissue architecture and morphorgenesis. Cell 84: 345–357.
  22. Humphries, M.J., A.P. Mould, K.M. Yamada (1991) Matrix receptors in cell migration; in McDonald, J.A., R.P. Mecham (eds): Receptors for Extracellular Matrix. San Diego, Academic Press, pp 195–253.
  23. Ilic, D., Y. Furuta, S. Kanazawa, N. Takeda, K. Sobue, N. Nakatsuji, S. Nomura, J. Fujimoto, M. Okada, T. Yamamoto (1995) Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice. Nature 377: 539–544.
  24. Jayaraman, M., U. Meyer, M. Buehner, U. Joos, H.P. Wiesmann (2004) Influence of titanium surfaces on attachment of osteoblast-like cells in vitro. Biomaterials 25: 625–631.
  25. Jessensky, O., F. Müller, U. Gösele (1998) Self-organized formation of hexagonal pore arrays in anodic alumina. Appl Phys Lett 72: 1173–1175.
  26. Keller, J.C., C.M. Stanford, J.P. Wightman, R.A. Draughn, R. Zaharias (1994) Characterization of titanium implant surfaces. III. J Biomed Mater Res 28: 939–946.
  27. Kieswetter, K., Z. Schwartz, D.D. Dean, B.D. Boyan (1996) The role of implant surface characteristics in the healing of bone. Crit Rev Oral Biol Med 7: 329–345.
  28. Pienta, K.J., R.H. Getzenberg, D.S. Coffey (1991) Cell structure and DNA organization. Crit Rev Eukaryot Gene Expr 1: 355–385.
  29. Postiglione, L., G. Di Domemnico, L. Ramaglia, S. Montagnani, S. Salzano, F. Di Meglio, L. Sbordone, M. Vitale, G. Rossi (2003) Behavior of SaOS-2 cells cultured on different titanium surfaces. J Dent Res 82: 692–696.
  30. Quake, S.R., A. Scherer (2000) From micro- to nanofabrication with soft materials. Science 290: 1536–1540.
  31. Rosen, J.J., L.A. Culp (1977) Morphology and cellular origins of substrate-attached material from mouse fibroblasts. Exp Cell Res 107: 139–149.
  32. Schwartz, J., M.J. Avaltroni, M.P. Danahy, B.M. Silverman, E.L. Hanson, J.E. Schwarzbauer, K.S. Midwood, E.S. Gawalt (2003) Cell attachment and spreading on metal implant materials. Mater Science and Engineering C 23: 395–400.

    External Resources

  33. Son, W., X. Zhu, H. Shin, J.L. Ong, K. Kim (2003) In vivo histological response to anodized and anodized/hydrothermally treated titanium implants. J Biomed Mater Res 66B: 520–525.
  34. Stangl, R., B. Rinne, S. Kastl, C. Hendrich (2001) The influence of pore geometry in cp Ti-implants – a cell culture investigation. Eur Cell Mater 2: 1–9.
  35. Steketee, M., K. Balazovich, K.W. Tosney (2001) Filopodial initiation and a novel filament-organizing center, the focal ring. Mol Biol Cell 12: 2378–2395.
  36. Sykaras, N., A.M. Iacopino, V.A. Marker, R.G. Triplett, R.D. Woody (2000) Implant materials, designs, and surface topographies: their effect on osseointegration. A literature review. Int J Oral Maxillofac Implants 15: 675–690.
  37. Tobasnick, G., A.S.G. Curtis (2001) Chloride channels and the reactions of cells to topography. Eur Cell Mater 2: 49–61.
  38. Voldman, J., M.L. Gray, M.A. Schmidt (1999) Microfabrication in biology and medicine. Annu Rev Biomed Eng 1: 401–425.
  39. Wilkinson, C.D.W., A.S.G. Curtis, J. Crossan (1998) Nanofabrication in cellular engineering. J Vac Sci Technol B16: 3132–3136.
  40. Wolosewick, J.J., Porter K.R. (1979) Microtrabecular lattice of the cytoplasmic ground substance. Artifact or reality. J Cell Biol 82: 114–139.
  41. Zhang S, L. Yan, M. Altman, M. Lässle, H. Nugent, F. Frankel, D.A. Lauffenburger, G.M. Whitesides, A. Rich (1999) Biological surface engineering: a simple system for cell pattern formation. Biomaterials 20: 1213–1220.
  42. Zhu, X., J. Chen, L. Scheideler, C. Schille, J. Geis-Gerstorfer (2003) In vitro osteoblast responses to anodic oxides containing Ca and P on titanium. J Dent Res 82: B-308.
  43. Zhu, X., K. Kim, Y. Jeong (2001) Anodic oxide films containing Ca and P of titanium biomaterial. Biomaterials 22: 2199–2206.
  44. Zhu, X., K. Kim, J.L. Ong, Y. Jeong (2002) Surface analysis of anodic oxide films containing phosphorus on titanium. Int J Oral Maxillofac Implants 17: 331–336.
  45. Zinger, O., K. Anselme, A. Denzer, P. Habersetzer, M. Wieland, J. Jeanfils, P. Hardouin, D. Landolt (2004) Time-dependent morphology and adhesion of osteoblastic cells on titanium model surfaces featuring scale-resolved topography. Biomaterials 25: 2695–2711.

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