Research Article

Cell differentiation and osseointegration influenced by nanoscale anodized titanium surfaces

Sandrine Lavenus

* Author for correspondence

Rensselaer Polytechnic Institute, Nanotecnology Center, Troy, NY 12180-3590, USA.

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Email the corresponding author at lavens@rpi.edu

Valérie Trichet

Inserm U957, Laboratory Physiopathology of Bone Resorption, Faculty of Medicine, University of Nantes, France

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Sébastien Le Chevalier

CNRS, Institut des Matériaux Jean Rouxel (IMN), University of Nantes, Nantes, France

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Alain Hoornaert

ERT 2004, Faculty of Dental Surgery, University of Nantes, Nantes, France

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Guy Louarn

CNRS, Institut des Matériaux Jean Rouxel (IMN), University of Nantes, Nantes, France

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Pierre Layrolle

Inserm U957, Laboratory Physiopathology of Bone Resorption, Faculty of Medicine, University of Nantes, France

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Published Online:30 Jul 2012https://doi.org/10.2217/nnm.11.181

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Abstract

Aims: We aimed to study the interactions between human mesenchymal stem cells and the bone integration of nanostructured titanium implants. Materials & methods: Nanopores of 20, 30 and 50 nm were prepared by anodization of titanium at 5, 10 and 20 V in a mixture of fluorhydric and acetic acid. Ti 30 and 50 nanostructures promoted early osteoblastic gene differentiation of the human mesenchymal stem cells without osteogenic supplements. The osseointegration of nanostructured and control titanium implants was compared by implantation in rat tibias for 1 and 3 weeks. Results: The nanostructures significantly accelerated bone apposition and bone bonding strength in vivo in correlation with in vitro results. Conclusion: These findings demonstrate that specific nanostructures controlled the differentiation of cells and, thus, the integration of implants in tissues. These nanoporous titanium surfaces may be of considerable interest for dental and orthopedic implants.

Original submitted 10 September 2011; Revised submitted 11 November 2011; Published online 6 March 2012

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References

1 Le Guéhennec L, Soueidan A, Layrolle P, Amouriq Y. Surface treatments of titanium dental implants for rapid osseointegration. Dent. Mater.23(7),844–854 (2007).Crossref, Medline, CAS, Google Scholar
2 Davies JE. Understanding peri-implant endosseous healing. J. Dent. Educ.67(8),932–949 (2003).Crossref, Medline, Google Scholar
3 Marco F, Milena F, Gianluca G, Vittoria O. Peri-implant osteogenesis in health and osteoporosis. Micron36(7–8),630–644 (2005).Crossref, Medline, CAS, Google Scholar
4 Cai K, Bossert J, Jandt KD. Does the nanometre scale topography of titanium influence protein adsorption and cell proliferation? Colloids Surf. B Biointerfaces49(2),136–144 (2006).Crossref, Medline, CAS, Google Scholar
5 Protivínský J, Appleford M, Strnad J, Helebrant A, Ong JL. Effect of chemically modified titanium surfaces on protein adsorption and osteoblast precursor cell behavior. Int. J. Oral Maxillofac. Implants22(4),542–550 (2007).Medline, Google Scholar
6 Zhao G, Raines AL, Wieland M, Schwartz Z, Boyan BD. Requirement for both micron- and submicron scale structure for synergistic responses of osteoblasts to substrate surface energy and topography. Biomaterials28(18),2821–2829 (2007).Crossref, Medline, CAS, Google Scholar
7 Yang Y, Tian J, Deng L, Ong JL. Morphological behavior of osteoblast-like cells on surface-modified titanium in vitro. Biomaterials23(5),1383–1389 (2002).Crossref, Medline, CAS, Google Scholar
8 Le Guehennec L. Osteoblastic cell behavior on nanostructured metal implants. Nanomedicine (Lond).3(1),61–71 (2008).Link, CAS, Google Scholar
9 Dalby MJ, Gadegaard N, Curtis ASG, Oreffo ROC. Nanotopographical control of human osteoprogenitor differentiation. Curr. Stem Cell Res. Ther.2(2),129–138 (2007).Crossref, Medline, CAS, Google Scholar
10 Dalby MJ, Gadegaard N, Tare R et al. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat. Mater.6(12),997–1003 (2007).Crossref, Medline, CAS, Google Scholar
11 Dalby MJ, McCloy, Robertson M, Wilkinson CDW, Oreffo RO. Osteoprogenitor response to defined topographies with nanoscale depths. Biomaterials27(8),1306–1315 (2006).Crossref, Medline, CAS, Google Scholar
12 Caplan AI. Why are MSCs therapeutic? New data: new insight. J. Pathol.217(2),318–324 (2009).Crossref, Medline, CAS, Google Scholar
13 Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J. Cell. Biochem.98(5),1076–1084 (2006).Crossref, Medline, CAS, Google Scholar
14 Kassem M. Stem cells: potential therapy for age-related diseases. Ann. NY Acad. Sci.1067,436–442 (2006).Crossref, Medline, CAS, Google Scholar
15 Marinucci L, Balloni S, Becchetti E et al. Effects of hydroxyapatite and Biostite on osteogenic induction of hMSC. Ann. Biomed. Eng.38(3),640–648 (2010).Crossref, Medline, Google Scholar
16 Lepski G, Jannes CE, Maciaczyk J et al. Limited Ca²⁺ and PKA-pathway dependent neurogenic differentiation of human adult mesenchymal stem cells as compared with fetal neuronal stem cells. Exp. Cell Res.316(2),216–231 (2010).Crossref, Medline, CAS, Google Scholar
17 Morganstein DL, Wu P, Mane MR, Fisk NM, White R, Parker MG. Human fetal mesenchymal stem cells differentiate into brown and white adipocytes: a role for ERRα in human UCP1 expression. Cell Res.20(4),434–444 (2010).Crossref, Medline, CAS, Google Scholar
18 Zannettino ACW, Paton S, Arthur A et al. Multipotential human adipose-derived stromal stem cells exhibit a perivascular phenotype in vitro and in vivo. J. Cell. Physiol.214(2),413–421 (2008).Crossref, Medline, CAS, Google Scholar
19 Engler AJ, Sen S, Sweeney HL, Discher DE. Matrix elasticity directs stem cell lineage specification. Cell126(4),677–689 (2006).Crossref, Medline, CAS, Google Scholar
20 Oh S, Brammer KS, Li YSJ et al. Stem cell fate dictated solely by altered nanotube dimension. Proc. Natl Acad. Sci. USA106(7),2130–2135 (2009).Crossref, Medline, CAS, Google Scholar
21 Park J, Bauer S, von der Mark K, Schmuki P. Nanosize and vitality: TiO₂ nanotube diameter directs cell fate. Nano Lett.7(6),1686–1691 (2007).Crossref, Medline, CAS, Google Scholar
22 Sul YT. Electrochemical growth behavior, surface properties, and enhanced in vivo bone response of TiO₂ nanotubes on microstructured surfaces of blasted, screw-shaped titanium implants. Int. J. Nanomedicine5,87–100 (2010).Crossref, Medline, CAS, Google Scholar
23 Sul YT, Johansson CB, Jeong Y, Röser K, Wennerberg A, Albrektsson T. Oxidized implants and their influence on the bone response. J. Mater. Sci. Mater. Med.12(10–12),1025–1031 (2001).Crossref, Medline, CAS, Google Scholar
24 Bjursten LM, Rasmusson L, Oh S, Smith GC, Brammer KS, Jin S. Titanium dioxide nanotubes enhance bone bonding in vivo. J. Biomed. Mater. Res. A92(3),1218–1224 (2010).Medline, Google Scholar
25 Le Guehennec L, Marco-Antonio, Benedicte, Weiss P, Amouriq Y, Layrolle P. Osteoblastic cell behaviour on different titanium implant surfaces. Acta Biomater.4(3),535–543 (2008).Crossref, Medline, CAS, Google Scholar
26 Kilian KA, Bugarija B, Lahn BT, Mrksich M. Geometric cues for directing the differentiation of mesenchymal stem cells. Proc. Natl Acad. Sci. USA107(11),4872–4877 (2010).Crossref, Medline, CAS, Google Scholar
27 Itano N, Okamoto S, Zhang D, Lipton SA, Ruoslahti E. Cell spreading controls endoplasmic and nuclear calcium: a physical gene regulation pathway from the cell surface to the nucleus. Proc. Natl Acad. Sci. USA.100(9),5181–5186 (2003).Crossref, Medline, CAS, Google Scholar
28 McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev. Cell6(4),483–495 (2004).Crossref, Medline, CAS, Google Scholar
29 Keene DR, Sakai LY, Burgeson RE. Human bone contains type III collagen, type VI collagen, and fibrillin: type III collagen is present on specific fibers that may mediate attachment of tendons, ligaments, and periosteum to calcified bone cortex. J. Histochem. Cytochem.39(1),59–69 (1991).Crossref, Medline, CAS, Google Scholar
30 Hong D, Chen HX, Yu HQ et al. Morphological and proteomic analysis of early stage of osteoblast differentiation in osteoblastic progenitor cells. Exp. Cell Res.316(14),2291–2300 (2010).Crossref, Medline, CAS, Google Scholar
31 Liu X, Wu H, Byrne M, Krane S, Jaenisch R. Type III collagen is crucial for collagen I fibrillogenesis and for normal cardiovascular development. Proc. Natl Acad. Sci. USA94(5),1852–1856 (1997).Crossref, Medline, CAS, Google Scholar
32 Kadler KE, Hojima Y, Prockop DJ. Collagen fibrils in vitro grow from pointed tips in the C- to N-terminal direction. Biochem. J.268(2),339–343 (1990).Crossref, Medline, CAS, Google Scholar
33 Chiquet M, Mumenthaler U, Wittwer M, Jin W, Koch M. The chick and human collagen α1(XII) gene promoter – activity of highly conserved regions around the first exon and in the first intron. Eur. J. Biochem.257(2),362–371 (1998).Crossref, Medline, CAS, Google Scholar
34 Singh SP, Chang EI, Gossain AK et al. Cyclic mechanical strain increases production of regulators of bone healing in cultured murine osteoblasts. J. Am. Coll. Surg.204(3),426–434 (2007).Crossref, Medline, Google Scholar
35 Lindahl GE, Chambers RC, Papakrivopoulou J et al. Activation of fibroblast procollagen α1(I) transcription by mechanical strain is transforming growth factor-β-dependent and involves increased binding of CCAAT-binding factor (CBF/NF-Y) at the proximal promoter. J. Biol. Chem.277(8),6153–6161 (2002).Crossref, Medline, CAS, Google Scholar
36 Arai K, Nagashima Y, Takemoto T, Nishiyama T. Mechanical strain increases expression of type XII collagen in murine osteoblastic MC3T3-E1 cells. Cell Struct. Funct.33(2),203–210 (2008).Crossref, Medline, CAS, Google Scholar
37 Tanaka Y, Morimoto I, Nakano Y et al. Osteoblasts are regulated by the cellular adhesion through ICAM-1 and VCAM-1. J. Bone Miner. Res.10(10),1462–1469 (1995).Crossref, Medline, CAS, Google Scholar
38 Di Cesare PE, Fang C, Leslie MP, Tulli H, Perris R, Carlson CS. Expression of cartilage oligomeric matrix protein (COMP) by embryonic and adult osteoblasts. J. Orthop. Res.18(5),713–720 (2000).Crossref, Medline, CAS, Google Scholar
39 DiCesare P, Hauser N, Lehman D, Pasumarti S, Paulsson M. Cartilage oligomeric matrix protein (COMP) is an abundant component of tendon. FEBS Lett.354(2),237–240 (1994).Crossref, Medline, CAS, Google Scholar
40 Halász K, Kassner A, Mörgelin M, Heinegård D. COMP acts as a catalyst in collagen fibrillogenesis. J. Biol. Chem.282(43),31166–31173 (2007).Crossref, Medline, CAS, Google Scholar
41 Briggs MD, Hoffman SM, King LM et al. Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene. Nat. Genet.10(3),330–336 (1995).Crossref, Medline, CAS, Google Scholar
42 Rosenberg K, Olsson H, Mörgelin M, Heinegård D. Cartilage oligomeric matrix protein shows high affinity zinc-dependent interaction with triple helical collagen. J. Biol. Chem.273(32),20397–20403 (1998).Crossref, Medline, CAS, Google Scholar
43 von Wilmowsky C, Bauer S, Lutz R et al.In vivo evaluation of anodic TiO₂ nanotubes: an experimental study in the pig. J. Biomed. Mater. Res. Part B Appl. Biomater.89(1),165–171 (2009).Crossref, Medline, Google Scholar
44 Bigerelle M, Anselme K, Noël B, Ruderman I, Hardouin P, Iost A. Improvement in the morphology of Ti-based surfaces: a new process to increase in vitro human osteoblast response. Biomaterials23(7),1563–1577 (2002).Crossref, Medline, CAS, Google Scholar
45 Buser D, Nydegger T, Oxland T et al. Interface shear strength of titanium implants with a sandblasted and acid-etched surface: a biomechanical study in the maxilla of miniature pigs. J. Biomed. Mater. Res.45(2),75–83 (1999).Crossref, Medline, CAS, Google Scholar
101 Tebu-bio. www.tebubio.comGoogle Scholar

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Published online 30 July 2012

Published in print July 2012

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Acknowledgements

The authors are grateful to M Berreur for her help with the PCR experiments. P Pilet and the microscopy center of U791 are acknowledged for their help.

Financial & competing interests disclosure

P Layrolle and A Hoornaert are founders of the spin-off company Biomedical Tissues, which produces biodegradable polymer nanofiber meshes for regeneration of human tissues. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. The authors are grateful to K Snaith of Medicis Traduction for grammar and spelling corrections of the manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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