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PLOS ONE  2014 

Nanometer Scale Titanium Surface Texturing Are Detected by Signaling Pathways Involving Transient FAK and Src Activations

DOI: 10.1371/journal.pone.0095662

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Background It is known that physico/chemical alterations on biomaterial surfaces have the capability to modulate cellular behavior, affecting early tissue repair. Such surface modifications are aimed to improve early healing response and, clinically, offer the possibility to shorten the time from implant placement to functional loading. Since FAK and Src are intracellular proteins able to predict the quality of osteoblast adhesion, this study evaluated the osteoblast behavior in response to nanometer scale titanium surface texturing by monitoring FAK and Src phosphorylations. Methodology Four engineered titanium surfaces were used for the study: machined (M), dual acid-etched (DAA), resorbable media microblasted and acid-etched (MBAA), and acid-etch microblasted (AAMB). Surfaces were characterized by scanning electron microscopy, interferometry, atomic force microscopy, x-ray photoelectron spectroscopy and energy dispersive X-ray spectroscopy. Thereafter, those 4 samples were used to evaluate their cytotoxicity and interference on FAK and Src phosphorylations. Both Src and FAK were investigated by using specific antibody against specific phosphorylation sites. Principal Findings The results showed that both FAK and Src activations were differently modulated as a function of titanium surfaces physico/chemical configuration and protein adsorption. Conclusions It can be suggested that signaling pathways involving both FAK and Src could provide biomarkers to predict osteoblast adhesion onto different surfaces.


[1]  Chuang SK, Cai T (2006) Predicting clustered dental implant survival using frailty methods. J Dent Res 85: 1147–51 doi:10.1177/154405910608501216.
[2]  Esposito M, Murray-Curtis L, Grusovin MG, Coulthard P, Worthington HV (2007) Interventions for replacing missing teeth: different types of dental implants. Cochrane Database Syst Rev 4: CD003815 doi:10.1002/14651858.CD003815.pub3.
[3]  Raes F, Cooper LF, Tarrida LG, Vandromme H, De Bruyn H (2012) A case-control study assessing oral-health-related quality of life after immediately loaded single implants in healed alveolar ridges or extraction sockets. Clinical oral implants research 23: 602–8 doi:10.1111/j.1600-0501.2011.02178.x.
[4]  Jimbo R, Sawase T, Shibata Y, Hirata K, Hishikawa Y, et al. (2007) Enhanced osseointegration by the chemotactic activity of plasma fibronectin for cellular fibronectin positive cells. Biomaterials 28: 3469–77 doi:10.1016/j.biomaterials.2007.04.029.
[5]  Coelho PG, Granjeiro JM, Romanos GE, Suzuki M, Silva NR, et al. (2009) Basic research methods and current trends of dental implant surfaces. J Biomed Mater Res B Appl Biomater 88: 579–96 doi:10.1002/jbm.b.31264.
[6]  Wennerberg A, Albrektsson T (2009) Effects of titanium surface topography on bone integration: a systematic review. Clinical oral implants research 20 Suppl 4172–84 doi:10.1111/j.1600-0501.2009.01775.x.
[7]  Wennerberg A, Albrektsson T (2009) Structural influence from calcium phosphate coatings and its possible effect on enhanced bone integration. Acta Odontol Scand 67: 1–8 doi:10.1080/00016350903188325.
[8]  Wennerberg A, Albrektsson T (2010) On implant surfaces: a review of current knowledge and opinions. The International journal of oral & maxillofacial implants 25: 63–74.
[9]  Meirelles L, Currie F, Jacobsson M, Albrektsson T, Wennerberg A (2008) The effect of chemical and nanotopographical modifications on the early stages of osseointegration. The International journal of oral & maxillofacial implants 23: 641–7.
[10]  Jimbo R, Coelho PG, Bryington M, Baldassarri M, Tovar N, et al. (2012) Nano hydroxyapatite-coated implants improve bone nanomechanical properties. Journal of dental research 91: 1172–7 doi:10.1177/0022034512463240.
[11]  Frojd V, Franke-Stenport V, Meirelles L, Wennerberg A (2008) Increased bone contact to a calcium-incorporated oxidized commercially pure titanium implant: an in-vivo study in rabbits. International journal of oral and maxillofacial surgery 37: 561–6 doi:10.1016/j.ijom.2008.01.020.
[12]  Cooper LF, Zhou Y, Takebe J, Guo J, Abron A, et al. (2006) Fluoride modification effects on osteoblast behavior and bone formation at TiO2 grit-blasted c.p. titanium endosseous implants. Biomaterials 27: 926–36 doi:10.1016/j.biomaterials.2005.07.009.
[13]  Monjo M, Lamolle SF, Lyngstadaas SP, R?nold HJ, Ellingsen JE (2008) In vivo expression of osteogenic markers and bone mineral density at the surface of fluoride-modified titanium implants. Biomaterials 29: 3771–80. doi: 10.1016/j.biomaterials.2008.06.001
[14]  Sul YT (2010) Electrochemical growth behavior, surface properties, and enhanced in vivo bone response of TiO2 nanotubes on microstructured surfaces of blasted, screw-shaped titanium implants. International journal of nanomedicine 5: 87–100 doi
[15]  Marin C, Granato R, Bonfante EA, Suzuki M, Janal MN, et al. (2012) Evaluation of a nanometer roughness scale resorbable media-processed surface: a study in dogs. Clin Oral Implants Res 23: 119–24 doi:10.1111/j.1600-0501.2010.02155.x.
[16]  Jimbo R, Coelho PG, Vandeweghe S, Schwartz-Filho HO, Hayashi M, et al. (2011) Histological and three-dimensional evaluation of osseointegration to nanostructured calcium phosphate-coated implants. Acta Biomater 7: 4229–34 doi:10.1016/j.actbio.2011.07.017.
[17]  Jimbo R, Xue Y, Hayashi M, Schwartz-Filho HO, Andersson M, et al. (2011) Genetic responses to nanostructured calcium-phosphate-coated implants. Journal of dental research 90: 1422–7 doi:10.1177/0022034511422911.
[18]  Sawase T, Jimbo R, Baba K, Shibata Y, Ikeda T, et al. (2008) Photo-induced hydrophilicity enhances initial cell behavior and early bone apposition. Clinical oral implants research 19: 491–6 doi:10.1111/j.1600-0501.2007.01509.x.
[19]  Jimbo R, Sawase T, Baba K, Kurogi T, Shibata Y, et al. (2008) Enhanced initial cell responses to chemically modified anodized titanium. Clinical implant dentistry and related research 10: 55–61 doi:10.1111/j.1708-8208.2007.00061.x.
[20]  Monjo M, Petzold C, Ramis JM, Lyngstadaas SP, Ellingsen JE (2012) In Vitro Osteogenic Properties of Two Dental Implant Surfaces. International Journal of Biomaterials 2012: 1–14 doi:10.1155/2012/181024.
[21]  Zhang W, Wang G, Liu Y, Zhao X, Zou D, et al. (2013) The synergistic effect of hierarchical micro/nano-topography and bioactive ions for enhanced osseointegration. Biomaterials 34: 3184–95 doi:10.1016/j.biomaterials.2013.01.008.
[22]  Zambuzzi WF, Bruni-Cardoso A, Granjeiro JM, Peppelenbosch MP, de Carvalho HF, et al. (2009) On the road to understanding of the osteoblast adhesion: cytoskeleton organization is rearranged by distinct signaling pathways. Journal of cellular biochemistry 108: 134–44 doi:10.1002/jcb.22236.
[23]  Zambuzzi WF, Milani R, Teti A (2010) Expanding the role of Src and protein-tyrosine phosphatases balance in modulating osteoblast metabolism: lessons from mice. Biochimie 92: 327–32 doi:10.1016/j.biochi.2010.01.002.
[24]  Zambuzzi WF, Ferreira CV, Granjeiro JM, Aoyama H (2011) Biological behavior of pre-osteoblasts on natural hydroxyapatite: A study of signaling molecules from attachment to differentiation. Journal of Biomedical Materials Research Part A 97A: 193–200 doi:10.1002/jbm.a.32933.
[25]  Wlodarski KH, Reddi AH (1986) Alkaline phosphatase as a marker of osteoinductive cells. Calcified tissue international 39: 382–5. doi: 10.1007/bf02555175
[26]  Gemini-Piperni S, Milani R, Bertazzo S, Peppelenbosch M, Takamori ER, et al. (2014) Kinome profiling of osteoblasts on hydroxyapatite opens new avenues on biomaterial cell signaling. Biotechnol Bioeng. doi:10.1002/bit.25246 [Epub ahead of print].
[27]  Lamolle SF, Monjo M, Rubert M, Haugen HJ, Lyngstadaas SP, et al. (2009) The effect of hydrofluoric acid treatment of titanium surface on nanostructural and chemical changes and the growth of MC3T3-E1 cells. Biomaterials 30: 736–42 doi:10.1016/j.biomaterials.2008.10.052.
[28]  Bertazzo S, Zambuzzi WF, da Silva HA, Ferreira CV, Bertran CA (2009) Bioactivation of alumina by surface modification: a possibility for improving the applicability of alumina in bone and oral repair. Clinical oral implants research 20: 288–93 doi:10.1111/j.1600-0501.2008.01642.x.
[29]  Bertazzo S, Zambuzzi WF, Campos DD, Ferreira CV, Bertran CA (2010) A simple method for enhancing cell adhesion to hydroxyapatite surface. Clinical oral implants research 21: 1411–3 doi:10.1111/j.1600-0501.2010.01968.x.
[30]  Milani R, Ferreira CV, Granjeiro JM, Paredes-Gamero EJ, Silva RA, et al. (2010) Phosphoproteome reveals an atlas of protein signaling networks during osteoblast adhesion. Journal of cellular biochemistry 109: 957–66 doi:10.1002/jcb.22479.
[31]  Saruwatari L, Aita H, Butz F, Nakamura HK, Ouyang J, et al. (2005) Osteoblasts Generate Harder, Stiffer, and More Delamination-Resistant Mineralized Tissue on Titanium Than on Polystyrene, Associated With Distinct Tissue Micro- and Ultrastructure. Journal of Bone and Mineral Research 20: 2002–16 doi:10.1359/JBMR.050703.
[32]  Shapira L, Halabi A (2009) Behavior of two osteoblast-like cell lines cultured on machined or rough titanium surfaces. Clinical oral implants research 20: 50–5 doi:10.1111/j.1600-0501.2008.01594.x.
[33]  Wei J, Shi Y, Zheng L, Zhou B, Inose H, et al. (2012) miR-34 s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2. The Journal of Cell Biology 197: 509–521 doi:10.1083/jcb.201201057.
[34]  Yang Q, Jian J, Abramson SB, Huang X (2011) Inhibitory effects of iron on bone morphogenetic protein 2–induced osteoblastogenesis. Journal of Bone and Mineral Research 26: 1188–1196 doi:10.1002/jbmr.337.
[35]  Lüthen F, Lange R, Becker P, Rychly J, Beck U, et al. (2005) The influence of surface roughness of titanium on beta1- and beta3-integrin adhesion and the organization of fibronectin in human osteoblastic cells. Biomaterials 26: 2423–40 doi:10.1016/j.biomaterials.2004.07.054.
[36]  Wilson CJ, Clegg RE, Leavesley DI, Pearcy MJ (2005) Mediation of biomaterial-cell interactions by adsorbed proteins: a review. Tissue Engineering 11: 1–18 doi:10.1089/ten.2005.11.1.
[37]  Sommerfeldt DW, McLeod KJ, Rubin CT, Hadjiargyrou M (2001) Differential phosphorylation of paxillin in response to surface-bound serum proteins during early osteoblast adhesion. Biochem Biophys Res Commun 285: 355–63 doi:10.1006/bbrc.2001.519.
[38]  Hoemann CD, El-Gabalawy H, McKee MD (2009) In vitro osteogenesis assays: influence of the primary cell source on alkaline phosphatase activity and mineralization. Pathologie-biologie 57: 318–23 doi:10.1016/j.patbio.2008.06.004.
[39]  de Souza Malaspina TS, Zambuzzi WF, dos Santos CX, Campanelli AP, Laurindo FR, et al. (2009) A possible mechanism of low molecular weight protein tyrosine phosphatase (LMW-PTP) activity modulation by glutathione action during human osteoblast differentiation. Archives of oral biology 54: 642–50 doi:10.1016/j.archoralbio.2009.03.011.


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