A comparative in vivo study of strontium-functionalized and SLActive™ implant surfaces in early bone healing

Apr 2018

A comparative in vivo study of strontium-functionalized and SLActiveTM implant surfaces in early bone healing Vincent Offermanns,1 Ole Z Andersen,2 Michael Sillassen,2 Klaus P Almtoft,3 Inge H Andersen,3 Frank Kloss,4 Morten Foss2,5 1Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Innsbruck, Innsbruck, Austria; 2Interdisciplinary Nanoscience Center (iNANO), Faculty of Science and Technology, Aarhus University, Aarhus, Denmark; 3Tribology Center, Danish Technological Institute, Aarhus, Denmark; 4Private Practice, Lienz, Austria; 5Department of Physics and Astronomy, Faculty of Science and Technology, Aarhus University, Aarhus, Denmark Purpose: Studies have shown that strontium-doped medical applications benefit bone metabolism leading to improved bone healing and osseointegration. Based on this knowledge, the aim of the study was to evaluate the performance of an implant surface, functionalized by a physical vapor deposition (PVD) coating (Ti-Sr-O), designed to yield predictable release of strontium. The Ti-Sr-O functionalized surface is compared to a routinely used, commercially available surface (SLActive™) with respect to bone-to-implant contact (BIC%) and new bone formation (BF%) in two defined regions of interest (ROI-I and ROI-II, respectively).Materials and methods: Ti-Sr-O functionalized, SLActive, and Grade 4 titanium implants were inserted in the femoral condyle of adult male New Zealand White rabbits. The PVD magnetron-sputtered Ti-Sr-O surface coating was characterized using scanning electron microscopy (SEM) for morphology and coating thickness. Strontium release and mechanical stability of the coating, under simulated insertion conditions, were evaluated. Furthermore, histomorphometrical BIC and BF were carried out 2 weeks after insertion.Results: Histomorphometry revealed increased bone formation of Ti-Sr-O with significant differences compared to SLActive and Grade 4 titanium in both regions of interest, ROI-I and ROI-II, at 0–250 µm and 250–500 µm distance from the implant surfaces. Analogous results of bone-to-implant contact were observed for the two modified surfaces. Conclusion: The results show that a nanopatterned Ti-Sr-O functionalized titanium surface, with sustained release of strontium, increases peri-implant bone volume and could potentially contribute to enhancement of bone anchorage of osseointegrated implants. Keywords: biofunctionalization, wettability, physical vapor deposition, bioactive, surface modification, bone

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A comparative in vivo study of strontium-functionalized and SLActive™ implant surfaces in early bone healing

International Journal of Nanomedicine Dovepress open access to scientific and medical research O r i g in a l R e s e a r c h International Journal of Nanomedicine downloaded from https://www.dovepress.com/ by 51.68.7.205 on 13-Jul-2018 For personal use only. Open Access Full Text Article A comparative in vivo study of strontiumfunctionalized and SLActive™ implant surfaces in early bone healing This article was published in the following Dove Press journal: International Journal of Nanomedicine Vincent Offermanns 1 Ole Z Andersen 2 Michael Sillassen 2 Klaus P Almtoft 3 Inge H Andersen 3 Frank Kloss 4 Morten Foss 2,5 Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Innsbruck, Innsbruck, Austria; 2 Interdisciplinary Nanoscience Center (iNANO), Faculty of Science and Technology, Aarhus University, Aarhus, Denmark; 3Tribology Center, Danish Technological Institute, Aarhus, Denmark; 4Private Practice, Lienz, Austria; 5Department of Physics and Astronomy, Faculty of Science and Technology, Aarhus University, Aarhus, Denmark 1 Purpose: Studies have shown that strontium-doped medical applications benefit bone metabolism leading to improved bone healing and osseointegration. Based on this knowledge, the aim of the study was to evaluate the performance of an implant surface, functionalized by a physical vapor deposition (PVD) coating (Ti-Sr-O), designed to yield predictable release of strontium. The Ti-Sr-O functionalized surface is compared to a routinely used, commercially available surface (SLActive™) with respect to bone-to-implant contact (BIC%) and new bone formation (BF%) in two defined regions of interest (ROI-I and ROI-II, respectively). Materials and methods: Ti-Sr-O functionalized, SLActive, and Grade 4 titanium implants were inserted in the femoral condyle of adult male New Zealand White rabbits. The PVD magnetron-sputtered Ti-Sr-O surface coating was characterized using scanning electron microscopy (SEM) for morphology and coating thickness. Strontium release and mechanical stability of the coating, under simulated insertion conditions, were evaluated. Furthermore, histomorphometrical BIC and BF were carried out 2 weeks after insertion. Results: Histomorphometry revealed increased bone formation of Ti-Sr-O with significant differences compared to SLActive and Grade 4 titanium in both regions of interest, ROI-I and ROI-II, at 0–250 µm and 250–500 µm distance from the implant surfaces. Analogous results of bone-to-implant contact were observed for the two modified surfaces. Conclusion: The results show that a nanopatterned Ti-Sr-O functionalized titanium surface, with sustained release of strontium, increases peri-implant bone volume and could potentially contribute to enhancement of bone anchorage of osseointegrated implants. Keywords: biofunctionalization, wettability, physical vapor deposition, bioactive, surface modification, bone Introduction Correspondence: Vincent Offermanns Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria Tel +43 512 504 24373 Email 2189 submit your manuscript | www.dovepress.com International Journal of Nanomedicine 2018:13 2189–2197 Dovepress © 2018 Offermanns 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. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/IJN.S161061 Powered by TCPDF (www.tcpdf.org) Implant insertion and subsequent prosthetic treatment has become a reliable method with predictable results in modern dentistry. Artificial root insertion is regarded as an effective treatment for several prosthetic clinical setups considering survival rates between 75% and 98% in defined observation periods and study groups.1,2 Nevertheless, in industrialized countries with influence of demographic changes in particular, different challenges remain. Elderly patients with compromised bone conditions3 due to, eg, osteoporosis, antiresorptive therapy, or patients having undergone irradiation with a need for oral rehabilitation represent a patient population with requisitions for further enhancement of endosseous implant devices. International Journal of Nanomedicine downloaded from https://www.dovepress.com/ by 51.68.7.205 on 13-Jul-2018 For personal use only. Offermanns et al Following the discovery of the phenomenon of osseointegration by Brånemark et al,4 research initially focused on implant geometry.5 This focus has now shifted toward biofunctionalization of surfaces aiming for acceleration of the biological process of osseointegration, allowing for early implant loading. Nowadays, different approaches for enhancement of surface properties are used, such as generation of defined geometries in the macro-, micro-, and nanometer range6 (eg, sandblasting and etching),7 implementation of osteoinductive ions,8 laser ablation,9 anodic oxidation,10 or preparation under N2 protection/storage in liquid resulting in ultrahydrophilic surfaces.11 The latter process with increased wettability was introduced in the last decade and evolved to a commonly used surface within dental implantology due to advanced surface free energy resulting in extended woven bone formation.11,12 Preclinical studies showed that SLActive™ implants achieved up to 60% more bone-to-implant contact 2 weeks post-insertion13 and demonstrated accelerated and more developed bone formation when compared to a conventional sandblasted and acid-etched surface.14 Incorporation and subsequent release of bioactive ions, eg, calcium (Ca), magnesium (Mg), or strontium (Sr), has been investigated in various applications,15–17 constituting beneficial effects on bone metabolism. Based on the documented effects in vitro, in vivo, as well as in clinical trials,17–19 strontium, an essential trace element in the human body, represents a promising route for enhancement of osseointegration with effects on osteogenic gene expression, cell differentiation, and increased bone apposition when introduced into, eg, bioabsorbable alloys, cements, bioglasses, composites, or surface coatings.20–24 The mechanisms through which strontium affects bone remodeling, with its dual effect on bone-forming osteoblasts and bone-resorbing osteoclasts, are still elusive. In vitro studies have shown that clinically used strontium ranelate (SrRan) affects the RANK/RANKL/OPG pathway25 as well as osteogenic differentiation of mesenchymal stem cells (MSCs), (...truncated)


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Vincent Offermanns, Ole Z Andersen, Michael Sillassen, Klaus P Almtoft, Inge H Andersen, Frank Kloss, Morten Foss. A comparative in vivo study of strontium-functionalized and SLActive™ implant surfaces in early bone healing, 2018, pp. 2189-2197, DOI: 10.2147/IJN.S161061