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      Laser-Modified Surface Enhances Osseointegration and Biomechanical Anchorage of Commercially Pure Titanium Implants for Bone-Anchored Hearing Systems

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          Abstract

          Osseointegrated implants inserted in the temporal bone are a vital component of bone-anchored hearing systems (BAHS). Despite low implant failure levels, early loading protocols and simplified procedures necessitate the application of implants which promote bone formation, bone bonding and biomechanical stability. Here, screw-shaped, commercially pure titanium implants were selectively laser ablated within the thread valley using an Nd:YAG laser to produce a microtopography with a superimposed nanotexture and a thickened surface oxide layer. State-of-the-art machined implants served as controls. After eight weeks’ implantation in rabbit tibiae, resonance frequency analysis (RFA) values increased from insertion to retrieval for both implant types, while removal torque (RTQ) measurements showed 153% higher biomechanical anchorage of the laser-modified implants. Comparably high bone area (BA) and bone-implant contact (BIC) were recorded for both implant types but with distinctly different failure patterns following biomechanical testing. Fracture lines appeared within the bone ~30–50 μm from the laser-modified surface, while separation occurred at the bone-implant interface for the machined surface. Strong correlations were found between RTQ and BIC and between RFA at retrieval and BA. In the endosteal threads, where all the bone had formed de novo, the extracellular matrix composition, the mineralised bone area and osteocyte densities were comparable for the two types of implant. Using resin cast etching, osteocyte canaliculi were observed directly approaching the laser-modified implant surface. Transmission electron microscopy showed canaliculi in close proximity to the laser-modified surface, in addition to a highly ordered arrangement of collagen fibrils aligned parallel to the implant surface contour. It is concluded that the physico-chemical surface properties of laser-modified surfaces (thicker oxide, micro- and nanoscale texture) promote bone bonding which may be of benefit in situations where large demands are imposed on biomechanically stable interfaces, such as in early loading and in compromised conditions.

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          Most cited references48

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          The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder.

          A key tenet of bone tissue engineering is the development of scaffold materials that can stimulate stem cell differentiation in the absence of chemical treatment to become osteoblasts without compromising material properties. At present, conventional implant materials fail owing to encapsulation by soft tissue, rather than direct bone bonding. Here, we demonstrate the use of nanoscale disorder to stimulate human mesenchymal stem cells (MSCs) to produce bone mineral in vitro, in the absence of osteogenic supplements. This approach has similar efficiency to that of cells cultured with osteogenic media. In addition, the current studies show that topographically treated MSCs have a distinct differentiation profile compared with those treated with osteogenic media, which has implications for cell therapies.
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            Surface treatments of titanium dental implants for rapid osseointegration.

            The osseointegration rate of titanium dental implants is related to their composition and surface roughness. Rough-surfaced implants favor both bone anchoring and biomechanical stability. Osteoconductive calcium phosphate coatings promote bone healing and apposition, leading to the rapid biological fixation of implants. The different methods used for increasing surface roughness or applying osteoconductive coatings to titanium dental implants are reviewed. Surface treatments, such as titanium plasma-spraying, grit-blasting, acid-etching, anodization or calcium phosphate coatings, and their corresponding surface morphologies and properties are described. Most of these surfaces are commercially available and have proven clinical efficacy (>95% over 5 years). The precise role of surface chemistry and topography on the early events in dental implant osseointegration remain poorly understood. In addition, comparative clinical studies with different implant surfaces are rarely performed. The future of dental implantology should aim to develop surfaces with controlled and standardized topography or chemistry. This approach will be the only way to understand the interactions between proteins, cells and tissues, and implant surfaces. The local release of bone stimulating or resorptive drugs in the peri-implant region may also respond to difficult clinical situations with poor bone quality and quantity. These therapeutic strategies should ultimately enhance the osseointegration process of dental implants for their immediate loading and long-term success.
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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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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 June 2016
                2016
                : 11
                : 6
                : e0157504
                Affiliations
                [1 ]Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden
                [2 ]BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden
                [3 ]Oticon Medical AB, Askim, Sweden
                University of Akron, UNITED STATES
                Author notes

                Competing Interests: MLJ and HS are under the employment of Oticon Medical AB. This (commercial affiliation) does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: MLJ OO PT. Performed the experiments: FAS MLJ OO HS AP. Analyzed the data: FAS MLJ OO HS AP PT. Wrote the paper: FAS MLJ OO HS AP PT.

                Author information
                http://orcid.org/0000-0002-9876-0467
                Article
                PONE-D-16-15181
                10.1371/journal.pone.0157504
                4907497
                27299883
                4d3db01e-01ee-45c5-aa3f-dd778181ed34
                © 2016 Shah et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 14 April 2016
                : 31 May 2016
                Page count
                Figures: 7, Tables: 4, Pages: 24
                Funding
                This study was supported by grants from Oticon Medical AB, the BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, the Västra Götaland Region, the Swedish Research Council (grant K2015-52X-09495-28-4), the ALF/LUA Research Grant “Optimization of osseointegration for treatment of transfemoral amputees” (ALFGBG-448851), the IngaBritt and Arne Lundberg Foundation, the Hjalmar Svensson Foundation, and the Vilhelm and Martina Lundgren Vetenskapsfond. FAS holds a PhD position financed by the Swedish Government Strategic Funding of Materials Science Area of Advance, provided to Chalmers and Department of Biomaterials, University of Gothenburg. MLJ holds an industrial PhD position financed by Oticon Medical AB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funder (Oticon Medical AB) provided support in the form of salaries for MLJ and HS, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
                Categories
                Research Article
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Connective Tissue Cells
                Osteoblasts
                Osteocytes
                Biology and Life Sciences
                Anatomy
                Biological Tissue
                Connective Tissue
                Connective Tissue Cells
                Osteoblasts
                Osteocytes
                Medicine and Health Sciences
                Anatomy
                Biological Tissue
                Connective Tissue
                Connective Tissue Cells
                Osteoblasts
                Osteocytes
                Physical Sciences
                Physics
                Classical Mechanics
                Motion
                Torque
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Bone Imaging
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Bone Imaging
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Bone Imaging
                Physical Sciences
                Physics
                Resonance
                Resonance Frequency
                Research and Analysis Methods
                Microscopy
                Electron Microscopy
                Scanning Electron Microscopy
                Physical Sciences
                Chemistry
                Chemical Elements
                Titanium
                Engineering and Technology
                Equipment
                Optical Equipment
                Lasers
                Biology and Life Sciences
                Anatomy
                Histology
                Medicine and Health Sciences
                Anatomy
                Histology
                Custom metadata
                The minimal data set underlying the major findings in the study has now been provided as Supporting Information.

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