In vivo evaluation of anodic TiO2 nanotubes: an experimental study in the pig.

Because of their ability to mimic the dimensions of constituent components of natural bone and the possibility to serve as a gene and drug-delivery carrier, nanotubes seem to be a promising coating for medical implants. Aim of this study was to investigate the effects of a TiO(2) nanotube structured surface on periimplant bone formation in vivo when compared with an untreated standard titanium surface. Twenty-five titanium implants covered with an ordered TiO(2) nanotube layer with an individual tube diameter of 30 nm and 25 commercially pure titanium (cp-Ti) implants were placed in the frontal skull of 25 domestic pigs. To evaluate the effects of the nanotube structured implants on the periimplant bone formation, bone-implant contact (BIC), and immunohistochemistry analysis were performed at day 3, 7, 14, 30, and 90. Evaluating immunohistochemistry, a significantly higher collagen type- I expression occurred at day 7 (p = 0.003), day 14 (p = 0.016), and day 30 (p = 0.044), for the nanostructured implants in comparison with the control group. It could be found that a nanotube structured implant surface with a diameter of 30 nm does influence bone formation and bone development by enhancing osteoblast function. SEM evaluation of the specimen surfaces revealed that the nanotube coatings do resist shearing forces that evoked by implant insertion. Because of their simple, low cost, flexible manufacturing and the possibility for the usage as drug or growth factor delivery system, nanotubes seem to be a promising method for future medical implant coatings.

[1]  T. Webster,et al.  Enhanced functions of osteoblasts on nanophase ceramics. , 2000, Biomaterials.

[2]  Jay R Lieberman,et al.  The role of growth factors in the repair of bone. Biology and clinical applications. , 2002, The Journal of bone and joint surgery. American volume.

[3]  J. Aubin,et al.  Cellular expression of bone‐related proteins during in vitro osteogenesis in rat bone marrow stromal cell cultures , 1994, Journal of cellular physiology.

[4]  Thomas Jay Webster,et al.  Nanomedicine for implants: a review of studies and necessary experimental tools. , 2007, Biomaterials.

[5]  C. R. Martin,et al.  Smart nanotubes for bioseparations and biocatalysis. , 2002, Journal of the American Chemical Society.

[6]  K. Donath,et al.  A method for the study of undecalcified bones and teeth with attached soft tissues. The Säge-Schliff (sawing and grinding) technique. , 1982, Journal of oral pathology.

[7]  R H Christenson,et al.  Biochemical markers of bone metabolism: an overview. , 1997, Clinical biochemistry.

[8]  Patrik Schmuki,et al.  Nanosize and vitality: TiO2 nanotube diameter directs cell fate. , 2007, Nano letters.

[9]  Marc Aucouturier,et al.  Anodic oxidation of titanium and TA6V alloy in chromic media. An electrochemical approach , 1999 .

[10]  Hans Söderlund,et al.  Antibody-Based Bio-Nanotube Membranes for Enantiomeric Drug Separations , 2002, Science.

[11]  K. Schlegel,et al.  Expression of bone matrix proteins during de novo bone formation using a bovine collagen and platelet-rich plasma (prp)--an immunohistochemical analysis. , 2005, Biomaterials.

[12]  Song Li,et al.  Enhanced cell attachment and osteoblastic activity by P-15 peptide-coated matrix in hydrogels. , 2003, Biochemical and biophysical research communications.

[13]  G. Stein,et al.  Progressive development of the rat osteoblast phenotype in vitro: Reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix , 1990, Journal of cellular physiology.

[14]  R. Swaminathan Biochemical markers of bone turnover. , 2001, Clinica chimica acta; international journal of clinical chemistry.

[15]  J. Qian,et al.  Design of biomimetic habitats for tissue engineering with P-15, a synthetic peptide analogue of collagen. , 1999, Tissue engineering.

[16]  Patrik Schmuki,et al.  Self-Organized Porous Titanium Oxide Prepared in H 2 SO 4 / HF Electrolytes , 2003 .

[17]  S. Heo,et al.  Osseointegration of anodized titanium implants under different current voltages: a rabbit study. , 2007, Journal of oral rehabilitation.

[18]  K. Donath,et al.  A method for the study of undecalcified bones and teeth with attached soft tissues. The sawing and grinding technique , 1982 .

[19]  Maxence Bigerelle,et al.  Effect of grooved titanium substratum on human osteoblastic cell growth. , 2002, Journal of biomedical materials research.

[20]  G. Jaeschke,et al.  [Clinical chemistry examinations of bone and muscle metabolism under stress in the Göttingen miniature pig--an experimental study]. , 1979, Berliner und Munchener tierarztliche Wochenschrift.

[21]  T. Webster,et al.  Specific proteins mediate enhanced osteoblast adhesion on nanophase ceramics. , 2000, Journal of biomedical materials research.

[22]  T. Albrektsson,et al.  Optimum surface properties of oxidized implants for reinforcement of osseointegration: surface chemistry, oxide thickness, porosity, roughness, and crystal structure. , 2005, The International journal of oral & maxillofacial implants.

[23]  Patrik Schmuki,et al.  TiO2 nanotubes : Tailoring the geometry in H3PO4/HF electrolytes , 2006 .

[24]  Michael Hahn,et al.  Enzyme and immunohistochemistry on undecalcified bone and bone marrow biopsies after embedding in plastic: A new embedding method for routine application , 2005, Virchows Archiv A.

[25]  F. Kloss,et al.  Bone conditioning to enhance implant osseointegration: an experimental study in pigs. , 2003, The International journal of oral & maxillofacial implants.

[26]  Thomas J Webster,et al.  Osteoblast function on nanophase alumina materials: Influence of chemistry, phase, and topography. , 2003, Journal of biomedical materials research. Part A.

[27]  H. Hansson,et al.  Osseointegrated titanium implants. Requirements for ensuring a long-lasting, direct bone-to-implant anchorage in man. , 1981, Acta orthopaedica Scandinavica.

[28]  H. G. Craighead,et al.  Chemical and topographical patterning for directed cell attachment , 2001 .

[29]  Patrik Schmuki,et al.  High-aspect-ratio TiO2 nanotubes by anodization of titanium. , 2005, Angewandte Chemie.

[30]  T. Martin,et al.  In situ hybridization to show sequential expression of osteoblast gene markers during bone formation in vivo , 1994, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[31]  J. Wiltfang,et al.  Expression of bone matrix proteins during the osseus healing of topical conditioned implants: an experimental study. , 2006, Clinical oral implants research.

[32]  T. Webster,et al.  Use of Anodized Titanium in Drug Delivery Applications , 2006 .