Titania Nanotubes for Local Drug Delivery from Implant Surfaces

  • Karan Gulati
  • Masakazu Kogawa
  • Shaheer Maher
  • Gerald Atkins
  • David Findlay
  • Dusan Losic
Chapter
Part of the Springer Series in Materials Science book series (SSMATERIALS, volume 220)

Abstract

The principal challenge for bone therapy is to deliver an effective dose of therapeutic agent (for example antibiotic or anti-cancer drug) to the affected site within bone, while sparing other organs. The solution to this dilemma is to deliver drug locally within the bone; hence various surface/therapeutic modifications of the conventional bone implants have been suggested to achieve this. Implants composed of biocompatible materials and loaded with active therapeutics thus provide one possible option for effective bone therapy. This chapter showcases the challenges that an electrochemically nano-engineered bone implant based on titania nanotubes must overcome to survive and deliver therapeutics in conditions such as infections and cancer of bone. The fabrication of titania nanotubes, the therapeutic loading and release, ex vivo and in vivo investigations; all are reviewed in terms of effectiveness for therapeutic action. Also discussed are the potential advances of titania nanotube technology and the future research directions to address additional clinical problems.

References

  1. 1.
    S.B. Goodman, Z. Yao, M. Keeney, F. Yang, The future of biologic coatings for orthopaedic implants. Biomaterials 34(13), 3174–3183 (2013)Google Scholar
  2. 2.
    A.K. Jain, R. Panchagnula, Skeletal drug delivery systems. Int. J. Pharm. 206(1–2), 1–12 (2000)Google Scholar
  3. 3.
    M. Geetha, A.K. Singh, R. Asokamani, A.K. Gogia, Ti based biomaterials, the ultimate choice for orthopaedic implants—A review. Prog. Mater. Sci. 54(3), 397–425 (2009)Google Scholar
  4. 4.
    D. Losic, S. Simovic, Self-ordered nanopore and nanotube platforms for drug delivery applications. Expert. Opin. Drug Deliv. 6(12), 1363–1381 (2009)Google Scholar
  5. 5.
    K. Gulati, M.S. Aw, D. Findlay, D. Losic, Local drug delivery to the bone by drug-releasing implants: perspectives of nano-engineered titania nanotube arrays. Ther. Deliv. 3(7), 857–873 (2012)Google Scholar
  6. 6.
    B. Trajkovski, A. Petersen, P. Strube, M. Mehta, G.N. Duda, Intra-operatively customized implant coating strategies for local and controlled drug delivery to bone. Adv. Drug Deliv. Rev. 64(12), 1142–1151 (2012)Google Scholar
  7. 7.
    H. Buchholz, R. Elson, E. Engelbrecht, H. Lodenkamper, J. Rottger, A. Siegel, Management of deep infection of total hip replacement. Bone Joint J. 63-B(3), 342–353 (1981)Google Scholar
  8. 8.
    D.A. Puleo, A. Nanci, Understanding and controlling the bone–implant interface. Biomaterials 20(23–24), 2311–2321 (1999)Google Scholar
  9. 9.
    D. Losic, M. S. Aw, A. Santos, K. Gulati, M. Bariana, Titania nanotube arrays for local drug delivery: recent advances and perspectives. Expert Opin. Drug Deliv. 1–25 (2014)Google Scholar
  10. 10.
    A. Santos, M. Sinn Aw, M. Bariana, T. Kumeria, Y. Wang, D. Losic, Drug-releasing implants: current progress, challenges and perspectives. J Mater. Chem. B 2(37), 6157–6182 (2014)Google Scholar
  11. 11.
    R. Bosco, J. Van Den Beucken, S. Leeuwenburgh, J. Jansen, Surface engineering for bone implants: A trend from passive to active surfaces. Coatings 2(3), 95–119 (2012)Google Scholar
  12. 12.
    S. Bauer, P. Schmuki, K. Von Der Mark, J. Park, Engineering biocompatible implant surfaces: Part I: materials and surfaces. Prog. Mater. Sci. 58(3), 261–326 (2013)Google Scholar
  13. 13.
    S. Hansson, M. Norton, The relation between surface roughness and interfacial shear strength for bone-anchored implants. A mathematical model. J. Biomech. 32(8), 829–836 (1999)Google Scholar
  14. 14.
    K. Kieswetter, Z. Schwartz, T.W. Hummert, D.L. Cochran, J. Simpson, D.D. Dean, B.D. Boyan, Surface roughness modulates the local production of growth factors and cytokines by osteoblast-like MG-63 cells. J. Biomed. Mater. Res. 32(1), 55–63 (1996)Google Scholar
  15. 15.
    S. Stea, L. Savarino, A. Toni, A. Sudanese, A. Giunti, A. Pizzoferrato, Microradiographic and histochemical evaluation of mineralization inhibition at the bone-alumina interface. Biomaterials 13(10), 664–667 (1992)Google Scholar
  16. 16.
    A. Wennerberg, The importance of surface roughness for implant incorporation. Int. J. Mach. Tool Manu. 38(5–6), 657–662 (1998)Google Scholar
  17. 17.
    A. Piattelli, M. Degidi, M. Paolantonio, C. Mangano, A. Scarano, Residual aluminum oxide on the surface of titanium implants has no effect on osseointegration. Biomaterials 24(22), 4081–4089 (2003)Google Scholar
  18. 18.
    A. Wennerberg, T. Albrektsson, B. Andersson, J.J. Krol, A histomorghometric study of screw-shaped and removal torque titanium implants with three different surface topographies. Clin. Oral Implants Res. 6(1), 24–30 (1995)Google Scholar
  19. 19.
    M. Wong, J. Eulenberger, R. Schenk, E. Hunziker, Effect of surface topology on the osseointegration of implant materials in trabecular bone. J. Biomed. Mater. Res. 29(12), 1567–1575 (1995)Google Scholar
  20. 20.
    L.F. Cooper, Y. Zhou, J. Takebe, J. Guo, A. Abron, A. Holmén, J.E. Ellingsen, Fluoride modification effects on osteoblast behavior and bone formation at TiO2 grit-blasted c.P. Titanium endosseous implants. Biomaterials 27(6), 926–936 (2006)Google Scholar
  21. 21.
    B. Yang, M. Uchida, H.-M. Kim, X. Zhang, T. Kokubo, Preparation of bioactive titanium metal via anodic oxidation treatment. Biomaterials 25(6), 1003–1010 (2004)Google Scholar
  22. 22.
    Y.T. Sul, C. Johansson, A. Wennerberg, L.R. Cho, B.S. Chang, T. Albrektsson, Optimum surface properties of oxidized implants for reinforcement of osseointegration: Surface chemistry, oxide thickness, porosity, roughness, and crystal structure. Int. J. Oral Maxillofac. Implants 20(3), 349–359 (2005)Google Scholar
  23. 23.
    X. Liu, P.K. Chu, C. Ding, Surface modification of titanium, titanium alloys, and related materials for biomedical applications. Mat. Sci. Eng. R: Rep. 47(3–4), 49–121 (2004)Google Scholar
  24. 24.
    T.A. Horbett, L.J. Brash, Proteins at interfaces: current issues and future prospects. In: Proteins at Interfaces, American Chemical Society, Chapter 1, pp 1–33 (1987)Google Scholar
  25. 25.
    J.E. Sundgren, P. Bodö, I. Lundström, Auger electron spectroscopic studies of the interface between human tissue and implants of titanium and stainless steel. J. Colloid Interface Sci. 110(1), 9–20 (1986)Google Scholar
  26. 26.
    L.D. Dorr, R. Bloebaum, J. Emmanual, R. Meldrum, Histologic, biochemical, and ion analysis of tissue and fluids retrieved during total hip arthroplasty. Clin. Orthop. Relat. Res. 261, 82–95 (1990)Google Scholar
  27. 27.
    J.J. Jacobs, A.K. Skipor, L.M. Patterson, N.J. Hallab, W.G. Paprosky, J. Black, J.O. Galante, Metal release in patients who have had a primary total hip arthroplasty. A prospective, controlled, longitudinal study. J. Bone Joint Surg. Am. 80(10), 1447–1458 (1998)Google Scholar
  28. 28.
    K.G. Nichols, D.A. Puleo, Effect of metal ions on the formation and function of osteoclastic cells in vitro. J. Biomed. Mater. Res. 35(2), 265–271 (1997)Google Scholar
  29. 29.
    R. Tejero, E. Anitua, G. Orive, Toward the biomimetic implant surface: Biopolymers on titanium-based implants for bone regeneration. Prog. Polym. Sci. 39(7), 1406–1447 (2014)Google Scholar
  30. 30.
    G. Schmidmaier, B. Wildemann, F. Cromme, F. Kandziora, N.P. Haas, M. Raschke, Bone morphogenetic protein-2 coating of titanium implants increases biomechanical strength and accelerates bone remodeling in fracture treatment: a biomechanical and histological study in rats. Bone 30(6), 816–822 (2002)Google Scholar
  31. 31.
    M. Yoshinari, Y. Oda, T. Inoue, K. Matsuzaka, M. Shimono, Bone response to calcium phosphate-coated and bisphosphonate-immobilized titanium implants. Biomaterials 23(14), 2879–2885 (2002)Google Scholar
  32. 32.
    J.G.E. Hendriks, J.R. Van Horn, H.C. Van Der Mei, H.J. Busscher, Backgrounds of antibiotic-loaded bone cement and prosthesis-related infection. Biomaterials 25(3), 545–556 (2004)Google Scholar
  33. 33.
    J. Parvizi, K.J. Saleh, P.S. Ragland, A.E. Pour, M.A. Mont, Efficacy of antibiotic-impregnated cement in total hip replacement. Acta Orthop. 79(3), 335–341 (2008)Google Scholar
  34. 34.
    K. Anagnostakos, O. Fürst, J. Kelm, Antibiotic-impregnated PMMA hip spacers: current status. Acta Orthop. 77(4), 628–637 (2006)Google Scholar
  35. 35.
    M.E. Shirtliff, J.H. Calhoun, J.T. Mader, Experimental osteomyelitis treatment with antibiotic-impregnated hydroxyapatite. Clin. Orthop. Relat. Res. 401, 239–247 (2002)Google Scholar
  36. 36.
    M. Gabriel, K. Nazmi, E.C. Veerman, A.V. Nieuw Amerongen, A. Zentner, Preparation of LL-37-grafted titanium surfaces with bactericidal activity. Bioconj. Chem. 17(2), 548–550 (2006)Google Scholar
  37. 37.
    P. Roy, S. Berger, P. Schmuki, TiO2 nanotubes: synthesis and applications. Angew. Chem. Int. Ed. 50(13), 2904–2939 (2011)Google Scholar
  38. 38.
    P. Hoyer, Formation of a titanium dioxide nanotube array. Langmuir 12(6), 1411–1413 (1996)Google Scholar
  39. 39.
    B.B. Lakshmi, P.K. Dorhout, C.R. Martin, Sol−gel template synthesis of semiconductor nanostructures. Chem. Mater. 9(3), 857–862 (1997)Google Scholar
  40. 40.
    T. Kasuga, M. Hiramatsu, A. Hoson, T. Sekino, K. Niihara, Titania nanotubes prepared by chemical processing. Adv. Mater. 11(15), 1307–1311 (1999)Google Scholar
  41. 41.
    M. Leskelä, M. Ritala, Atomic layer deposition chemistry: recent developments and future challenges. Angew. Chem. Int. Ed. 42(45), 5548–5554 (2003)Google Scholar
  42. 42.
    Y.R. Smith, B. Sarma, S.K. Mohanty, M. Misra, Light-assisted anodized TiO2 nanotube arrays. ACS Appl. Mater. Interfaces 4(11), 5883–5890 (2012)Google Scholar
  43. 43.
    M.P. Neupane, I.S. Park, T.S. Bae, M.H. Lee, Sonochemical assisted synthesis of nano-structured titanium oxide by anodic oxidation. J. Alloy. Compd. 581, 418–422 (2013)Google Scholar
  44. 44.
    V. Zwilling, M. Aucouturier, E. Darque-Ceretti, Anodic oxidation of titanium and TA6 V alloy in chromic media. An electrochemical approach. Electrochim. Acta 45(6), 921–929 (1999)Google Scholar
  45. 45.
    V. Zwilling, E. Darque-Ceretti, A. Boutry-Forveille, D. David, M.Y. Perrin, M. Aucouturier, Structure and physicochemistry of anodic oxide films on titanium and TA6Valloy. Surf. Interface Anal. 27(7), 629–637 (1999)Google Scholar
  46. 46.
    J.M. Macak, H. Tsuchiya, P. Schmuki, High-aspect-ratio TiO2 nanotubes by anodization of titanium. Angew. Chem. Int. Ed. 44(14), 2100–2102 (2005)Google Scholar
  47. 47.
    J.M. Macak, H. Tsuchiya, L. Taveira, S. Aldabergerova, P. Schmuki, Smooth anodic TiO2 nanotubes. Angew. Chem. Int. Ed. 44(45), 7463–7465 (2005)Google Scholar
  48. 48.
    J.M. Macak, K. Sirotna, P. Schmuki, Self-organized porous titanium oxide prepared in Na2SO4/NaF electrolytes. Electrochim. Acta 50(18), 3679–3684 (2005)Google Scholar
  49. 49.
    H.E. Prakasam, K. Shankar, M. Paulose, O.K. Varghese, C.A. Grimes, A new benchmark for TiO2 nanotube array growth by anodization. J. Phys. Chem. C 111(20), 7235–7241 (2007)Google Scholar
  50. 50.
    M. Paulose, H.E. Prakasam, O.K. Varghese, L. Peng, K.C. Popat, G.K. Mor, T.A. Desai, C.A. Grimes, TiO2 nanotube arrays of 1000 μm length by anodization of titanium foil: Phenol red diffusion. J. Phys. Chem. C 111(41), 14992–14997 (2007)Google Scholar
  51. 51.
    N.K. Allam, C.A. Grimes, Formation of vertically oriented TiO2 nanotube arrays using a fluoride free HCl aqueous electrolyte. J. Phys. Chem. C 111(35), 13028–13032 (2007)Google Scholar
  52. 52.
    S.P. Albu, D. Kim, P. Schmuki, Growth of aligned TiO2 bamboo-type nanotubes and highly ordered nanolace. Angew. Chem. 120(10), 1942–1945 (2008)Google Scholar
  53. 53.
    J. Yu, D. Wang, Y. Huang, X. Fan, X. Tang, C. Gao, J. Li, D. Zou, K. Wu, A cylindrical core-shell-like TiO2 nanotube array anode for flexible fiber-type dye-sensitized solar cells. Nanoscale Res. Lett. 6(1), 94 (2011)Google Scholar
  54. 54.
    K. Gulati, M.S. Aw, D. Losic, Drug-eluting Ti wires with titania nanotube arrays for bone fixation and reduced bone infection. Nanoscale Res. Lett. 6(1), 571 (2011)Google Scholar
  55. 55.
    Q.Y. Zeng, M. Xi, W. Xu, X.J. Li, Preparation of titanium dioxide nanotube arrays on titanium mesh by anodization in (NH4)2SO4/NH4F electrolyte. Mater. Corros. 64(11), 1001–1006 (2013)Google Scholar
  56. 56.
    L. Sun, X. Wang, M. Li, S. Zhang, Q. Wang, Anodic titania nanotubes grown on titanium tubular electrodes. Langmuir 30(10), 2835–2841 (2014)Google Scholar
  57. 57.
    K. Gulati, M.S. Aw, D. Losic, Nanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain. Int. J. Nanomed. 7, 2069–2076 (2012)Google Scholar
  58. 58.
    M.S. Aw, K.A. Khalid, K. Gulati, G.J. Atkins, P. Pivonka, D.M. Findlay, D. Losic, Characterization of drug-release kinetics in trabecular bone from titania nanotube implants. Int. J. Nanomed. 7, 4883–4892 (2012)Google Scholar
  59. 59.
    K. Gulati, G.J. Atkins, D.M. Findlay, D. Losic, Nano-engineered titanium for enhanced bone therapy, Proc SPIE 8812. Biosensing Nanomed. VI, 88120C (September 11, 2013). doi:10.1117/12.2027151
  60. 60.
    M. Long, H.J. Rack, Titanium alloys in total joint replacement—a materials science perspective. Biomaterials 19(18), 1621–1639 (1998)Google Scholar
  61. 61.
    J.M. Macak, H. Tsuchiya, L. Taveira, A. Ghicov, P. Schmuki, Self-organized nanotubular oxide layers on Ti-6Al-7Nb and Ti-6Al-4V formed by anodization in NH4F solutions. J. Biomed. Mater. Res. A 75A(4), 928–933 (2005)Google Scholar
  62. 62.
    X.J. Feng, J.M. Macak, S.P. Albu, P. Schmuki, Electrochemical formation of self-organized anodic nanotube coating on Ti–28ZR–8Nb biomedical alloy surface. Acta Biomater. 4(2), 318–323 (2008)Google Scholar
  63. 63.
    K. Yasuda, P. Schmuki, Control of morphology and composition of self-organized zirconium titanate nanotubes formed in (NH4)2SO4/NH4F electrolytes. Electrochim. Acta 52(12), 4053–4061 (2007)Google Scholar
  64. 64.
    H. Jha, R. Hahn, P. Schmuki, Ultrafast oxide nanotube formation on TiNb, TiZr and TiTa alloys by rapid breakdown anodization. Electrochim. Acta 55(28), 8883–8887 (2010)Google Scholar
  65. 65.
    Y.Q. Liang, Z.D. Cui, S.L. Zhu, X.J. Yang, Characterization of self-organized TiO2 nanotubes on Ti–4Zr–22Nb–2Sn alloys and the application in drug delivery system. J. Mater. Sci. Mater. Med. 22(3), 461–467 (2011)Google Scholar
  66. 66.
    L. Wang, T.T. Zhao, Z. Zhang, G. Li, Fabrication of highly ordered TiO2 nanotube arrays via anodization of ti-6al-4v alloy sheet. J. Nanosci. Nanotechnol. 10(12), 8312–8321 (2010)Google Scholar
  67. 67.
    E. Feschet-Chassot, V. Raspal, Y. Sibaud, O.K. Awitor, F. Bonnemoy, J.L. Bonnet, J. Bohatier, Tunable functionality and toxicity studies of titanium dioxide nanotube layers. Thin Solid Films 519(8), 2564–2568 (2011)Google Scholar
  68. 68.
    B.D. Boyan, T.W. Hummert, D.D. Dean, Z. Schwartz, Role of material surfaces in regulating bone and cartilage cell response. Biomaterials 17(2), 137–146 (1996)Google Scholar
  69. 69.
    K. Gulati, S. Ramakrishnan, M.S. Aw, G.J. Atkins, D.M. Findlay, D. Losic, Biocompatible polymer coating of titania nanotube arrays for improved drug elution and osteoblast adhesion. Acta Biomater. 8(1), 449–456 (2012)Google Scholar
  70. 70.
    K.C. Popat, L. Leoni, C.A. Grimes, T.A. Desai, Influence of engineered titania nanotubular surfaces on bone cells. Biomaterials 28(21), 3188–3197 (2007)Google Scholar
  71. 71.
    K.C. Popat, M. Eltgroth, T.J. Latempa, C.A. Grimes, T.A. Desai, Decreased staphylococcus epidermis adhesion and increased osteoblast functionality on antibiotic-loaded titania nanotubes. Biomaterials 28(32), 4880–4888 (2007)Google Scholar
  72. 72.
    L. Peng, M.L. Eltgroth, T.J. Latempa, C.A. Grimes, T.A. Desai, The effect of TiO2 nanotubes on endothelial function and smooth muscle proliferation. Biomaterials 30(7), 1268–1272 (2009)Google Scholar
  73. 73.
    P. Neacsu, A. Mazare, A. Cimpean, J. Park, M. Costache, P. Schmuki, I. Demetrescu, Reduced inflammatory activity of raw 264.7 macrophages on titania nanotube modified Ti surface. Int. J. Biochem. Cell Biol. 55, 187–195 (2014)Google Scholar
  74. 74.
    L.M. Bjursten, L. Rasmusson, S. Oh, G.C. Smith, K.S. Brammer, S. Jin, Titanium dioxide nanotubes enhance bone bonding in vivo. J. Biomed. Mater. Res. A. 92A(3), 1218–1224 (2010)Google Scholar
  75. 75.
    W.C. Schroer, K.R. Berend, A.V. Lombardi, C.L. Barnes, M.P. Bolognesi, M.E. Berend, M.A. Ritter, R.M. Nunley, Why are total knees failing today? Etiology of total knee revision in 2010 and 2011. J. Arthroplasty 28(8, Supplement), 116–119 (2013)Google Scholar
  76. 76.
    S. Franz, S. Rammelt, D. Scharnweber, J.C. Simon, Immune responses to implants—a review of the implications for the design of immunomodulatory biomaterials. Biomaterials 32(28), 6692–6709 (2011)Google Scholar
  77. 77.
    B.D. Ratner, The engineering of biomaterials exhibiting recognition and specificity. J. Mol. Recognit. 9(5–6), 617–625 (1996)Google Scholar
  78. 78.
    C. Rungsiyakull, Q. Li, G. Sun, W. Li, M.V. Swain, Surface morphology optimization for osseointegration of coated implants. Biomaterials 31(27), 7196–7204 (2010)Google Scholar
  79. 79.
    K.M. Ainslie, S.L. Tao, K.C. Popat, H. Daniels, V. Hardev, C.A. Grimes, T.A. Desai, In vitro inflammatory response of nanostructured titania, silicon oxide, and polycaprolactone. J. Biomed. Mater. Res. A 91A(3), 647–655 (2009)Google Scholar
  80. 80.
    B.S. Smith, P. Capellato, S. Kelley, M. Gonzalez-Juarrero, K.C. Popat, Reduced in vitro immune response on titania nanotube arrays compared to titanium surface. Biomater. Sci. 1(3), 322–332 (2013)Google Scholar
  81. 81.
    G.E. Aninwene, C. Yao, T.J. Webster, Enhanced osteoblast adhesion to drug-coated anodized nanotubular titanium surfaces. Int. J. Nanomed. 3(2), 257–264 (2008)Google Scholar
  82. 82.
    S.S. Mandal, D. Jose, A.J. Bhattacharyya, Role of surface chemistry in modulating drug release kinetics in titania nanotubes. Mater. Chem. Phys. 147(1–2), 247–253 (2014)Google Scholar
  83. 83.
    T. Shokuhfar, S. Sinha-Ray, C. Sukotjo, A.L. Yarin, Intercalation of anti-inflammatory drug molecules within TiO2 nanotubes. RSC Adv. 3(38), 17380–17386 (2013)Google Scholar
  84. 84.
    M. Aw, K. Gulati, D. Losic, Controlling drug release from titania nanotube arrays using polymer nanocarriers and biopolymer coating. Biomater. Nanobiotechnol. 2, 477–484 (2011)Google Scholar
  85. 85.
    M.S. Aw, M. Kurian, D. Losic, Non-eroding drug-releasing implants with ordered nanoporous and nanotubular structures: concepts for controlling drug release. Biomater. Sci. 2(1), 10–34 (2014)Google Scholar
  86. 86.
    C.R. Hauck, K. Ohlsen, Sticky connections: Extracellular matrix protein recognition and integrin-mediated cellular invasion by staphylococcus aureus. Curr. Opin. Microbiol. 9(1), 5–11 (2006)Google Scholar
  87. 87.
    A. Gristina, Biomaterial-centered infection: microbial adhesion versus tissue integration. Science 237(4822), 1588–1595 (1987)Google Scholar
  88. 88.
    N.J. Hickok, I.M. Shapiro, Immobilized antibiotics to prevent orthopaedic implant infections. Adv Drug Del Rev. 64(12), 1165–1176 (2012)Google Scholar
  89. 89.
    J.W. Costerton, P.S. Stewart, E.P. Greenberg, Bacterial biofilms: A common cause of persistent infections. Science 284(5418), 1318–1322 (1999)Google Scholar
  90. 90.
    S.S. Rogers, C. Van Der Walle, T.A. Waigh, Microrheology of bacterial biofilms in vitro: staphylococcus aureus and pseudomonas aeruginosa. Langmuir 24(23), 13549–13555 (2008)Google Scholar
  91. 91.
    S.D. Puckett, E. Taylor, T. Raimondo, T.J. Webster, The relationship between the nanostructure of titanium surfaces and bacterial attachment. Biomaterials 31(4), 706–713 (2010)Google Scholar
  92. 92.
    B. Ercan, T. Erik, A. Ece, J.W. Thomas, Diameter of titanium nanotubes influences anti-bacterial efficacy. Nanotechnology 22(29), 295102 (2011)Google Scholar
  93. 93.
    T. Das, P.K. Sharma, H.J. Busscher, H.C. Van Der Mei, B.P. Krom, Role of extracellular DNA in initial bacterial adhesion and surface aggregation. Appl. Environ. Microbiol. 76(10), 3405–3408 (2010)Google Scholar
  94. 94.
    H. Zhang, Y. Sun, A. Tian, X.X. Xue, L. Wang, A. Alquhali, X. Bai, Improved antibacterial activity and biocompatibility on vancomycin-loaded TiO2 nanotubes: in vivo and in vitro studies. Int. J. Nanomed. 8, 4379–4389 (2013)Google Scholar
  95. 95.
    M. Kazemzadeh-Narbat, J. Kindrachuk, K. Duan, H. Jenssen, R.E.W. Hancock, R. Wang, Antimicrobial peptides on calcium phosphate-coated titanium for the prevention of implant-associated infections. Biomaterials 31(36), 9519–9526 (2010)Google Scholar
  96. 96.
    M. Ma, M. Kazemzadeh-Narbat, Y. Hui, S. Lu, C. Ding, D.D.Y. Chen, R.E.W. Hancock, R. Wang, Local delivery of antimicrobial peptides using self-organized TiO2 nanotube arrays for peri-implant infections. J. Biomed. Mater. Res. A 100A(2), 278–285 (2012)Google Scholar
  97. 97.
    L. Zhao, H. Wang, K. Huo, L. Cui, W. Zhang, H. Ni, Y. Zhang, Z. Wu, P.K. Chu, Antibacterial nano-structured titania coating incorporated with silver nanoparticles. Biomaterials 32(24), 5706–5716 (2011)Google Scholar
  98. 98.
    K. Huo, X. Zhang, H. Wang, L. Zhao, X. Liu, P.K. Chu, Osteogenic activity and antibacterial effects on titanium surfaces modified with Zn-incorporated nanotube arrays. Biomaterials 34(13), 3467–3478 (2013)Google Scholar
  99. 99.
    T. Kumeria, H. Mon, M.S. Aw, K. Gulati, H.J. Griesser, D. Losic, Advanced biopolymer-coated drug-releasing titania nanotubes (TNTs) implants with simultaneously enhanced osteoblast adhesion and antibacterial properties (2015) (unpublished)Google Scholar
  100. 100.
    X. Chen, K. Cai, J. Fang, M. Lai, Y. Hou, J. Li, Z. Luo, Y. Hu, L. Tang, Fabrication of selenium-deposited and chitosan-coated titania nanotubes with anticancer and antibacterial properties. Colloids Surf. B Biointerfaces 103, 149–157 (2013)Google Scholar
  101. 101.
    B. Ercan, K.M. Kummer, K.M. Tarquinio, T.J. Webster, Decreased staphylococcus aureus biofilm growth on anodized nanotubular titanium and the effect of electrical stimulation. Acta Biomater. 7(7), 3003–3012 (2011)Google Scholar
  102. 102.
    J.L. Del Pozo, M.S. Rouse, J.N. Mandrekar, J.M. Steckelberg, R. Patel, The electricidal effect: Reduction of staphylococcus and pseudomonas biofilms by prolonged exposure to low-intensity electrical current. Antimicrob. Agents Chemother. 53(1), 41–45 (2009)Google Scholar
  103. 103.
    A. Chug, S. Shukla, L. Mahesh, S. Jadwani, Osseointegration—molecular events at the bone–implant interface: A review. J. Oral Maxillofac. Surg. 25(1), 1–4 (2013)Google Scholar
  104. 104.
    C. Yao, V. Perla, J.L. Mckenzie, E.B. Slamovich, T.J. Webster, Anodized ti and Ti6Al4 V possessing nanometer surface features enhances osteoblast adhesion. J. Biomed. Nanotech. 1(1), 68–73 (2005)Google Scholar
  105. 105.
    T.J. Webster, J.U. Ejiofor, Increased osteoblast adhesion on nanophase metals: Ti, Ti6Al4V, and CoCrMo. Biomaterials 25(19), 4731–4739 (2004)Google Scholar
  106. 106.
    C. Von Wilmowsky, S. Bauer, R. Lutz, M. Meisel, F.W. Neukam, T. Toyoshima, P. Schmuki, E. Nkenke, K.A. Schlegel, In vivo evaluation of anodic TiO2 nanotubes: an experimental study in the pig. J. Biomed. Mater. Res. B Appl. Biomater. 89B(1), 165–171 (2009)Google Scholar
  107. 107.
    M.P. Neupane, I.S. Park, T.S. Bae, H.K. Yi, M. Uo, F. Watari, M.H. Lee, Titania nanotubes supported gelatin stabilized gold nanoparticles for medical implants. J. Mater. Chem. 21(32), 12078–12082 (2011)Google Scholar
  108. 108.
    L. Zhao, H. Wang, K. Huo, X. Zhang, W. Wang, Y. Zhang, Z. Wu, P.K. Chu, The osteogenic activity of strontium loaded titania nanotube arrays on titanium substrates. Biomaterials 34(1), 19–29 (2013)Google Scholar
  109. 109.
    J. Kunze, L. Müller, J.M. Macak, P. Greil, P. Schmuki, F.A. Müller, Time-dependent growth of biomimetic apatite on anodic TiO2 nanotubes. Electrochim. Acta 53(23), 6995–7003 (2008)Google Scholar
  110. 110.
    A. Kar, K.S. Raja, M. Misra, Electrodeposition of hydroxyapatite onto nanotubular TiO2 for implant applications. Surf. Coat. Technol. 201(6), 3723–3731 (2006)Google Scholar
  111. 111.
    A. Kodama, S. Bauer, A. Komatsu, H. Asoh, S. Ono, P. Schmuki, Bioactivation of titanium surfaces using coatings of TiO2 nanotubes rapidly pre-loaded with synthetic hydroxyapatite. Acta Biomater. 5(6), 2322–2330 (2009)Google Scholar
  112. 112.
    Y.-X. Gu, J. Du, J.-M. Zhao, M.-S. Si, J.-J. Mo, H.-C. Lai, Characterization and preosteoblastic behavior of hydroxyapatite-deposited nanotube surface of titanium prepared by anodization coupled with alternative immersion method. J. Biomed. Mater. Res. B Appl. Biomater. 100B(8), 2122–2130 (2012)Google Scholar
  113. 113.
    S. Oh, S. Jin, Titanium oxide nanotubes with controlled morphology for enhanced bone growth. Mater. Sci. Eng. C 26(8), 1301–1306 (2006)Google Scholar
  114. 114.
    T.N. Vo, F.K. Kasper, A.G. Mikos, Strategies for controlled delivery of growth factors and cells for bone regeneration. Adv. Drug Deliv. Rev. 64(12), 1292–1309 (2012)Google Scholar
  115. 115.
    M. Lai, K. Cai, L. Zhao, X. Chen, Y. Hou, Z. Yang, Surface functionalization of TiO2 nanotubes with Bone Morphogenetic Protein 2 and its synergistic effect on the differentiation of mesenchymal stem cells. Biomacromolecules 12(4), 1097–1105 (2011)Google Scholar
  116. 116.
    Y. Hu, K. Cai, Z. Luo, D. Xu, D. Xie, Y. Huang, W. Yang, P. Liu, Tio2 nanotubes as drug nanoreservoirs for the regulation of mobility and differentiation of mesenchymal stem cells. Acta Biomater. 8(1), 439–448 (2012)Google Scholar
  117. 117.
    T.-H. Koo, J. Borah, Z.C. Xing, S.M. Moon, Y. Jeong, I.K. Kang, Immobilization of pamidronic acids on the nanotube surface of titanium discs and their interaction with bone cells. Nanoscale Res. Lett. 8(1), 1–9 (2013)Google Scholar
  118. 118.
    S.J. Lee, T.J. Oh, T.S. Bae, M.H. Lee, Y. Soh, B.I. Kim, H.S. Kim, Effect of bisphosphonates on anodized and heat-treated titanium surfaces: an animal experimental study. J. Periodontol. 82(7), 1035–1042 (2010)Google Scholar
  119. 119.
    H. Wei, S. Wu, Z. Feng, W. Zhou, Y. Dong, G. Wu, S. Bai, Y. Zhao, Increased fibroblast functionality on CNN2-loaded titania nanotubes. Int. J. Nanomed. 7, 1091–1100 (2012)Google Scholar
  120. 120.
    S. Sun, W. Yu, Y. Zhang, F. Zhang, Increased preosteoblast adhesion and osteogenic gene expression on TiO2 nanotubes modified with KRSR. J. Mater. Sci. Mater. Med. 24(4), 1079–1091 (2013)Google Scholar
  121. 121.
    E. Gultepe, D. Nagesha, S. Sridhar, M. Amiji, Nanoporous inorganic membranes or coatings for sustained drug delivery in implantable devices. Adv. Drug Deliv. Rev. 62(3), 305–315 (2010)Google Scholar
  122. 122.
    L. Peng, A.D. Mendelsohn, T.J. Latempa, S. Yoriya, C.A. Grimes, T.A. Desai, Long-term small molecule and protein elution from TiO2 nanotubes. Nano Lett. 9(5), 1932–1936 (2009)Google Scholar
  123. 123.
    C. Yao, T.J. Webster, Prolonged antibiotic delivery from anodized nanotubular titanium using a co-precipitation drug loading method. J. Biomed. Mater. Res. B Appl. Biomater. 91B(2), 587–595 (2009)Google Scholar
  124. 124.
    I. De Santo, L. Sanguigno, F. Causa, T. Monetta, P.A. Netti, Exploring doxorubicin localization in eluting TiO2 nanotube arrays through fluorescence correlation spectroscopy analysis. Analyst 137(21), 5076–5081 (2012)Google Scholar
  125. 125.
    C.M. Han, E.J. Lee, H.E. Kim, Y.H. Koh, J.H. Jang, Porous TiO2 films on Ti implants for controlled release of tetracycline-hydrochloride (TCH). Thin Solid Films 519(22), 8074–8076 (2011)Google Scholar
  126. 126.
    M.S. Aw, J. Addai-Mensah, D. Losic, A multi-drug delivery system with sequential release using titania nanotube arrays. Chem. Commun. 48(27), 3348–3350 (2012)Google Scholar
  127. 127.
    M.S. Aw, J. Addai-Mensah, D. Losic, Magnetic-responsive delivery of drug-carriers using titania nanotube arrays. J. Mater. Chem. 22(14), 6561–6563 (2012)Google Scholar
  128. 128.
    M.S. Aw, D. Losic, Ultrasound enhanced release of therapeutics from drug-releasing implants based on titania nanotube arrays. Int. J. Pharm. 443(1–2), 154–162 (2013)Google Scholar
  129. 129.
    Y.Y. Song, F. Schmidt-Stein, S. Bauer, P. Schmuki, Amphiphilic TiO2 nanotube arrays: an actively controllable drug delivery system. J. Am. Chem. Soc. 131(12), 4230–4232 (2009)Google Scholar
  130. 130.
    S. Simovic, D. Losic, K. Vasilev, Controlled drug release from porous materials by plasma polymer deposition. Chem. Commun. 46(8), 1317–1319 (2010)Google Scholar
  131. 131.
    K. Vasilev, Z. Poh, K. Kant, J. Chan, A. Michelmore, D. Losic, Tailoring the surface functionalities of titania nanotube arrays. Biomaterials 31(3), 532–540 (2010)Google Scholar
  132. 132.
    A.J. Collins, J.A. Cosh, Temperature and biochemical studies of joint inflammation. A preliminary investigation. Ann. Rheum. Dis. 29(4), 386–392 (1970)Google Scholar
  133. 133.
    K. Cai, F. Jiang, Z. Luo, X. Chen, Temperature-responsive controlled drug delivery system based on titanium nanotubes. Adv. Eng. Mater. 12(9), B565–B570 (2010)Google Scholar
  134. 134.
    N.K. Shrestha, J.M. Macak, F. Schmidt-Stein, R. Hahn, C.T. Mierke, B. Fabry, P. Schmuki, Magnetically guided titania nanotubes for site-selective photocatalysis and drug release. Angew. Chem. Int. Ed. 48(5), 969–972 (2009)Google Scholar
  135. 135.
    S. Sirivisoot, R.A. Pareta, T.J. Webster, A conductive nanostructured polymer electrodeposited on titanium as a controllable, local drug delivery platform. J. Biomed. Mater. Res. A 99A(4), 586–597 (2011)Google Scholar
  136. 136.
    S. Sirivisoot, P. Rajesh, J.W. Thomas, Electrically controlled drug release from nanostructured polypyrrole coated on titanium. Nanotechnology 22(8), 085101 (2011)Google Scholar
  137. 137.
    M. Bariana, M.S. Aw, E. Moore, N.H. Voelcker, D. Losic, Radiofrequency-triggered release for on-demand delivery of therapeutics from titania nanotube drug-eluting implants. Nanomedicine 9(8), 1263–1275 (2013)Google Scholar
  138. 138.
    S. Sirivisoot, Y. Chang, X. Xingcheng, W.S. Brian, J.W. Thomas, Greater osteoblast functions on multiwalled carbon nanotubes grown from anodized nanotubular titanium for orthopedic applications. Nanotechnology 18(36), 365102 (2007)Google Scholar
  139. 139.
    S. Sirivisoot, J.W. Thomas, Multiwalled carbon nanotubes enhance electrochemical properties of titanium to determine in situ bone formation. Nanotechnology. 19(29), 295101 (2008)Google Scholar
  140. 140.
    D.B. Jones, E. Broeckmann, T. Pohl, E.L. Smith, Development of a mechanical testing and loading system for trabecular bone studies for long term culture. Eur. Cell Mater. 5, 48–59 (2003)Google Scholar
  141. 141.
    C.M. Davies, D.B. Jones, M.J. Stoddart, K. Koller, E. Smith, C.W. Archer, R.G. Richards, Mechanically loaded ex vivo bone culture system ‘zetos’: systems and culture preparation. Eur. Cell Mater. 11, 57–75 (2006)Google Scholar
  142. 142.
    S. Minagar, J. Wang, C.C. Berndt, E.P. Ivanova, C. Wen, Cell response of anodized nanotubes on titanium and titanium alloys. J. Biomed. Mater. Res. A 101A(9), 2726–2739 (2013)Google Scholar
  143. 143.
    J. Xiao, H. Zhou, L. Zhao, Y. Sun, S. Guan, B. Liu, L. Kong, The effect of hierarchical micro/nanosurface titanium implant on osseointegration in ovariectomized sheep. Osteoporosis Int. 22(6), 1907–1913 (2011)Google Scholar
  144. 144.
    K. Vandamme, X. Holy, M. Bensidhoum, D. Logeart-Avramoglou, I.E. Naert, J.A. Duyck, H. Petite, In vivo molecular evidence of delayed titanium implant osseointegration in compromised bone. Biomaterials 32(14), 3547–3554 (2011)Google Scholar
  145. 145.
    N. Harmankaya, J. Karlsson, A. Palmquist, M. Halvarsson, K. Igawa, M. Andersson, P. Tengvall, Raloxifene and alendronate containing thin mesoporous titanium oxide films improve implant fixation to bone. Acta Biomater. 9, 7064–7073 (2013)Google Scholar
  146. 146.
    J.M. Park, J.Y. Koak, J.H. Jang, C.H. Han, S.K. Kim, S.J. Heo, Osseointegration of anodized titanium implants coated with fibroblast growth factor-fibronectin (FGF-FN) fusion protein. Int. J. Oral Maxillofac. Implants 21(6), 859–866 (2006)Google Scholar
  147. 147.
    R. Adell, B. Eriksson, U. Lekholm, P.I. Brånemark, T. Jemt, Long-term follow-up study of osseointegrated implants in the treatment of totally edentulous jaws. Int. J. Oral Maxillofac. Implants 5(4), 347–359 (1990)Google Scholar
  148. 148.
    E.K. Moioli, P.A. Clark, X. Xin, S. Lal, J.J. Mao, Matrices and scaffolds for drug delivery in dental, oral and craniofacial tissue engineering. Adv. Drug Deliv. Rev. 59(4–5), 308–324 (2007)Google Scholar
  149. 149.
    Q. Ma, S. Mei, K. Ji, Y. Zhang, P.K. Chu, Immobilization of Ag nanoparticles/FGF-2 on a modified titanium implant surface and improved human gingival fibroblasts behavior. J. Biomed. Mater. Res. A 98A(2), 274–286 (2011)Google Scholar
  150. 150.
    Y.-H. Lee, G. Bhattarai, I.-S. Park, G.-R. Kim, G.-E. Kim, M.-H. Lee, H.-K. Yi, Bone regeneration around n-acetyl cysteine-loaded nanotube titanium dental implant in rat mandible. Biomaterials 34(38), 10199–10208 (2013)Google Scholar
  151. 151.
    I. Demetrescu, C. Pirvu, V. Mitran, Effect of nano-topographical features of Ti/TiO2 electrode surface on cell response and electrochemical stability in artificial saliva. Bioelectrochemistry 79(1), 122–129 (2010)Google Scholar
  152. 152.
    M. Kalbacova, J.M. Macak, F. Schmidt-Stein, C.T. Mierke, P. Schmuki, Tio2 nanotubes: Photocatalyst for cancer cell killing. Phys. Status Solidi Rapid Res. Lett. 2(4), 194–196 (2008)Google Scholar
  153. 153.
    Q. Li, X. Wang, X. Lu, H. Tian, H. Jiang, G. Lv, D. Guo, C. Wu, B. Chen, The incorporation of daunorubicin in cancer cells through the use of titanium dioxide whiskers. Biomaterials 30(27), 4708–4715 (2009)Google Scholar
  154. 154.
    P. Mccarthy, K. Otto, M. Rao, Robust penetrating microelectrodes for neural interfaces realized by titanium micromachining. Biomed. Microdevices 13(3), 503–515 (2011)Google Scholar
  155. 155.
    Y. Wang, J. Wang, X. Deng, J. Wang, H. Wang, M. Wu, Z. Jiao, Y. Liu, Direct imaging of titania nanotubes located in mouse neural stem cell nuclei. Nano Res. 2(7), 543–552 (2009)Google Scholar
  156. 156.
    World Health Organization (WHO), Medical device regulations. Global overview and guiding principles (2003)Google Scholar
  157. 157.
    J.S. Tsuji, A.D. Maynard, P.C. Howard, J.T. James, C.-W. Lam, D.B. Warheit, A.B. Santamaria, Research strategies for safety evaluation of nanomaterials, part IV: risk assessment of nanoparticles. Toxicol. Sci. 89(1), 42–50 (2006)Google Scholar
  158. 158.
    Y. Nuevo-Ordóñez, M. Montes-Bayón, E. Blanco-González, J. Paz-Aparicio, J.D. Raimundez, J.M. Tejerina, M.A. Peña, A. Sanz-Medel, Titanium release in serum of patients with different bone fixation implants and its interaction with serum biomolecules at physiological levels. Anal. Bioanal. Chem. 401(9), 2747–2754 (2011)Google Scholar
  159. 159.
    X. Li, L. Wang, Y. Fan, Q. Feng, F.-Z. Cui, Biocompatibility and toxicity of nanoparticles and nanotubes. J. Nanomat. 2012, 548389 (2012)Google Scholar
  160. 160.
    C.M. Sayes, R. Wahi, P.A. Kurian, Y. Liu, J.L. West, K.D. Ausman, D.B. Warheit, V.L. Colvin, Correlating nanoscale titania structure with toxicity: A cytotoxicity and inflammatory response study with human dermal fibroblasts and human lung epithelial cells. Toxicol. Sci. 92(1), 174–185 (2006)Google Scholar
  161. 161.
    N. Wang, H. Li, W. Lü, J. Li, J. Wang, Z. Zhang, Y. Liu, Effects of TiO2 nanotubes with different diameters on gene expression and osseointegration of implants in minipigs. Biomaterials 32(29), 6900–6911 (2011)Google Scholar
  162. 162.
    G.C. Smith, L. Chamberlain, L. Faxius, G.W. Johnston, S. Jin, L.M. Bjursten, Soft tissue response to titanium dioxide nanotube modified implants. Acta Biomater. 7(8), 3209–3215 (2011)Google Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Karan Gulati
    • 1
  • Masakazu Kogawa
    • 2
  • Shaheer Maher
    • 1
    • 3
  • Gerald Atkins
    • 2
  • David Findlay
    • 2
  • Dusan Losic
    • 1
  1. 1.School of Chemical EngineeringUniversity of AdelaideAdelaideAustralia
  2. 2.Discipline of Orthopaedics & TraumaUniversity of AdelaideAdelaideAustralia
  3. 3.Faculty of PharmacyAssiut UniversityAssiutEgypt

Personalised recommendations