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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

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      Biological and osseointegration capabilities of hierarchically (meso-/micro-/nano-scale) roughened zirconia

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          Abstract

          Purpose

          Zirconia is a potential alternative to titanium for dental and orthopedic implants. Here we report the biological and bone integration capabilities of a new zirconia surface with distinct morphology at the meso-, micro-, and nano-scales.

          Methods

          Machine-smooth and roughened zirconia disks were prepared from yttria-stabilized tetragonal zirconia polycrystal (Y-TZP), with rough zirconia created by solid-state laser sculpting. Morphology of the surfaces was analyzed by three-dimensional imaging and profiling. Rat femur-derived bone marrow cells were cultured on zirconia disks. Zirconia implants were placed in rat femurs and the strength of osseointegration was evaluated by biomechanical push-in test.

          Results

          The rough zirconia surface was characterized by meso-scale (50 µm wide, 6–8 µm deep) grooves, micro-scale (1–10 µm wide, 0.1–3 µm deep) valleys, and nano-scale (10–400 nm wide, 10–300 nm high) nodules, whereas the machined surface was flat and uniform. The average roughness (Ra) of rough zirconia was five times greater than that of machined zirconia. The expression of bone-related genes such as collagen I, osteopontin, osteocalcin, and BMP-2 was 7–25 times upregulated in osteoblasts on rough zirconia at the early stage of culture. The number of attached cells and rate of proliferation were similar between machined and rough zirconia. The strength of osseointegration for rough zirconia was twice that of machined zirconia at weeks two and four of healing, with evidence of mineralized tissue persisting around rough zirconia implants as visualized by electron microscopy and elemental analysis.

          Conclusion

          This unique meso-/micro-/nano-scale rough zirconia showed a remarkable increase in osseointegration compared to machine-smooth zirconia associated with accelerated differentiation of osteoblasts. Cell attachment and proliferation were not compromised on rough zirconia unlike on rough titanium. This is the first report introducing a rough zirconia surface with distinct hierarchical morphology and providing an effective strategy to improve and develop zirconia implants.

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          Most cited references98

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          Effects of titanium surface topography on bone integration: a systematic review.

          To analyse possible effects of titanium surface topography on bone integration. Our analyses were centred on a PubMed search that identified 1184 publications of assumed relevance; of those, 1064 had to be disregarded because they did not accurately present in vivo data on bone response to surface topography. The remaining 120 papers were read and analysed, after removal of an additional 20 papers that mainly dealt with CaP-coated and Zr implants; 100 papers remained and formed the basis for this paper. The bone response to differently configurated surfaces was mainly evaluated by histomorphometry (bone-to-implant contact), removal torque and pushout/pullout tests. A huge number of the experimental investigations have demonstrated that the bone response was influenced by the implant surface topography; smooth (S(a) 1-2 microm) surfaces showed stronger bone responses than rough (S(a)>2 microm) in some studies. One limitation was that it was difficult to compare many studies because of the varying quality of surface evaluations; a surface termed 'rough' in one study was not uncommonly referred to as 'smooth' in another; many investigators falsely assumed that surface preparation per se identified the roughness of the implant; and many other studies used only qualitative techniques such as SEM. Furthermore, filtering techniques differed or only height parameters (S(a), R(a)) were reported. * Surface topography influences bone response at the micrometre level. * Some indications exist that surface topography influences bone response at the nanometre level. * The majority of published papers present an inadequate surface characterization. * Measurement and evaluation techniques need to be standardized. * Not only height descriptive parameters but also spatial and hybrid ones should be used.
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            Advancing dental implant surface technology--from micron- to nanotopography.

            Current trends in clinical dental implant therapy include use of endosseous dental implant surfaces embellished with nanoscale topographies. The goal of this review is to consider the role of nanoscale topographic modification of titanium substrates for the purpose of improving osseointegration. Nanotechnology offers engineers and biologists new ways of interacting with relevant biological processes. Moreover, nanotechnology has provided means of understanding and achieving cell specific functions. The various techniques that can impart nanoscale topographic features to titanium endosseous implants are described. Existing data supporting the role of nanotopography suggest that critical steps in osseointegration can be modulated by nanoscale modification of the implant surface. Important distinctions between nanoscale and micron-scale modification of the implant surface are presently considered. The advantages and disadvantages of nanoscale modification of the dental implant surface are discussed. Finally, available data concerning the current dental implant surfaces that utilize nanotopography in clinical dentistry are described. Nanoscale modification of titanium endosseous implant surfaces can alter cellular and tissue responses that may benefit osseointegration and dental implant therapy.
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              High surface energy enhances cell response to titanium substrate microstructure.

              Titanium (Ti) is used for implantable devices because of its biocompatible oxide surface layer. TiO2 surfaces that have a complex microtopography increase bone-to-implant contact and removal torque forces in vivo and induce osteoblast differentiation in vitro. Studies examining osteoblast response to controlled surface chemistries indicate that hydrophilic surfaces are osteogenic, but TiO2 surfaces produced until now exhibit low surface energy because of adsorbed hydrocarbons and carbonates from the ambient atmosphere or roughness induced hydrophobicity. Novel hydroxylated/hydrated Ti surfaces were used to retain high surface energy of TiO2. Osteoblasts grown on this modified surface exhibited a more differentiated phenotype characterized by increased alkaline phosphatase activity and osteocalcin and generated an osteogenic microenvironment through higher production of PGE2 and TGF-beta1. Moreover, 1alpha,25OH2D3 increased these effects in a manner that was synergistic with high surface energy. This suggests that increased bone formation observed on modified Ti surfaces in vivo is due in part to stimulatory effects of high surface energy on osteoblasts. (c) 2005 Wiley Periodicals, Inc.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2018
                08 June 2018
                : 13
                : 3381-3395
                Affiliations
                Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, UCLA School of Dentistry, Los Angeles, CA, USA
                Author notes
                Correspondence: Takahiro Ogawa, Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, UCLA School of Dentistry, 10833 Le Conte Avenue (B3-081 CHS), Box 951668, Los Angeles, CA 90095-1668, USA, Tel +1 310 825 0727, Fax +1 310 825 6345, Email togawa@ 123456dentistry.ucla.edu
                Article
                ijn-13-3381
                10.2147/IJN.S159955
                5997135
                29922058
                20472427-f7e2-448f-abfd-6bab077ddbbb
                © 2018 Rezaei et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Molecular medicine
                bone–implant integration,y-tzp,hierarchical morphology,multi-scale rough,dental and orthopedic implant

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