| 1. |
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| 2. |
- Andersson, Marcus, 1975, et al.
(författare)
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Effect of molecular mobility of polymeric implants on soft tissue reactions: An in vivo study in rats
- 2008
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Ingår i: Journal of Biomedical Materials Research Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 84A:3, s. 652-660
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Tidskriftsartikel (refereegranskat)abstract
- Although numerous different polymers are used as implants or otherwise studied for many other biotechnical applications, there is a lack of basic models that correlate polymer characteristics with foreign body reactions. This study aims at developing one such model by systematically studying surface molecular mobility of polymeric implants in soft tissues in vivo. Changing the length of the alkyl side chain of poly(alkyl methacrylates) (PAMAs), provides an interesting opportunity to study the surface molecular mobility with minimal changes of the hydrophobicity of the surface. Thus, in this study three different PAMAs, with increasingly surface mobility; poly (isobutyl methacrylate) (PIBMA), poly(butyl methacrylate) (PBMA), and poly(lauryl methacralate) (PLMA) along with pure titanium (Ti) substrates were implanted in the dorsum of Sprague-Dawley rats. Inflammatory cell recruitment, cell adhesion, and cytokine release were studied after 1, 3, and 28 days of implantation. Total number of inflammatory cells in the exudate was measured but no correlation between surface mobility and cell recruitment where found. However, the number of surface associated cells where significantly lower on the surfaces with high molecular mobility (PLMA and PBMA). The histological evaluation performed after 28 days revealed thicker fibrous capsule and a higher number of blood vessels on the low molecular mobility surface (PIBMA). After 28 days the cell activity was higher on the high molecular mobility surfaces (PLMA and PBMA) compared with PIBMA, based on the cytokine release. None of the surfaces induced any significant cell-death. On the basis of the results of this study we conclude that there is a significant difference in biological response to surfaces with different in molecular mobility. This might affect the wound healing process and the biocompatibility of biomaterials. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007 -------------------------------------------------------------------------------- Received: 13 March 2006; Revised: 15 December 2006; Accepted: 29 January 2007 Digital Object Identifier (DOI) 10.1002/jbm.a.31389 About DOI
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Omar, Omar, et al.
(författare)
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In vivo gene expression in response to anodically oxidized versus machined titanium implants.
- 2010
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Ingår i: Journal of biomedical materials research. Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 92:4, s. 1552-1566
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Tidskriftsartikel (refereegranskat)abstract
- A quantitative polymerase chain reaction technique (qPCR) in combination with scanning electron microscopy was applied for the evaluation of early gene expression response and cellular reactions close to titanium implants. Anodically oxidized and machined titanium miniscrews were inserted in rat tibiae. After 1, 3, and 6 days the implants were unscrewed and the surrounding bone was retrieved using trephines. Both the implants and bone were analyzed with qPCR. A greater amount of cells, as indicated with higher expression of 18S, was detected on the oxidized surface after 1 and 6 days. Significantly higher osteocalcin (at day 6), alkaline phosphatase (at days 3 and 6), and cathepsin K (at day 3) expression was demonstrated for the oxidized surface. Higher expression of tumor necrosis factor-alpha (at day 1) and interleukin-1beta (at days 1 and 6) was detected on the machined surfaces. SEM revealed a higher amount of mesenchymal-like cells on the oxidized surface. The results show that the rapid recruitment of mesenchymal cells, the rapid triggering of gene expression crucial for bone remodeling and the transient nature of inflammation, constitute biological mechanisms for osseointegration, and high implant stability associated with anodically oxidized implants. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2009.
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| 7. |
- Omar, Omar, et al.
(författare)
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Integrin and chemokine receptor gene expression in implant-adherent cells during early osseointegration.
- 2010
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Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 1573-4838 .- 0957-4530. ; 21:3, s. 969-80
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms of early cellular recruitment and interaction to titanium implants are not well understood. The aim of this study was to investigate the expression of pro-inflammatory cytokines, chemokines and adhesion markers during the first 24 h of implantation. Anodically oxidized and machined titanium implants were inserted in rat tibia. After 3, 12, and 24 h the implants were unscrewed and analyzed with quantitative polymerase chain reaction. Immunohistochemistry and scanning electron microscopy revealed different cell types, morphology and adhesion at the two implant surfaces. A greater amount of cells, as indicated by higher expression of small subunit ribosomal RNA (18S), was detected on the oxidized surface. Higher expression of CXC chemokine receptor-4 (at 12 h) and integrins, alphav (at 12 h), beta1 (at 24 h) and beta2 (at 12 and 24 h) was detected at the oxidized surfaces. Significantly higher tumor necrosis factor-alpha (at 3 h) and interleukin-1beta (at 24 h) expression was demonstrated for the machined surface. It is concluded that material surface properties rapidly modulate the expression of receptors important for the recruitment and adhesion of cells which are crucial for the inflammatory and regenerative processes at implant surfaces in vivo.
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| 8. |
- Omar, Omar, et al.
(författare)
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Interfacial gene expression and stability of oxidized and machined titanium implants
- 2010
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Ingår i: European Association for Osseointegration 19th Annual Scientific Meeting, Glasgow, UK, 6-9 October, 2010.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In previous studies, combination of experimental model and gene expression analysis showed that from 3 hours to 6 days of implantation, significant differences in expression of genes denoting for cellular recruitment, inflammation, bone formation and bone resorption were seen at the interfaces of screw-shaped oxidized and machined titanium implants. It was concluded that the modulation of gene expression in favor of osteogenic differentiation and downregulation of the pro-inflammatory responses might explain the improved osseointegration of the oxidized implant surfaces. However, as a major condition, the developed bone-implant interface needs to be mechanically stable in order to fulfill the requirements of osseointegration The aim of the current study was to combine in vivo interfacial gene expression model with torque analysis in order to determine how molecular and cellular events taking place at the different titanium implants are related to the biomechanical properties of the interface. Anodically oxidized and machined titanium miniscrews were inserted in tibiae of 6 rats. Each rat received two oxidized implants in one tibia and two machined implants in the opposite tibia. After 28 days, the implants were removed using torque measuring equipment. The torque was registered and the implants completely removed and analyzed with quantitative polymerase chain reaction (n=12). Wilcoxon signed rank test was used to analyze the statistical differences of biomechanical and gene expression results between the two implant types. In addition, similar oxidized and machined titanium miniscrews were characterized topographically, chemically and ultrastructurally using profilometry, Auger electron microscopy and cross-sectioning electron microscopy, respectively. For chemical and topographical analyses, 3 implants from each type were analyzed. The measurements were made on flanks, tops, and valleys of two nonadjacent threads giving a total of 18 measurements for each implant type. Topographical comparisons were performed using one-way ANOVA followed by Bonferroni’s test. The biomechanical evaluation demonstrated 190% increase in torque values for the oxidized implants as compared to the machined ones. At the same time (28d), oxidized implants showed significantly higher expression of Runt-related transcription factor 1, osteocalcin, and tartrate resistant acid phosphatase. On the other hand higher expression of tumor necrosis factor-α and interleukin-1β was detected on the machined surfaces. Surface characterization procedures revealed major differences in the physico-chemical properties of the implant surfaces. In conclusion, the favorable cellular and molecular events at the oxidized implants were in parallel with significantly stronger bone anchorage during osseointegration
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| 9. |
- Omar, Omar, et al.
(författare)
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The correlation between gene expression of proinflammatory markers and bone formation during osseointegration with titanium implants
- 2011
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612. ; 32:2, s. 374-86
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Tidskriftsartikel (refereegranskat)abstract
- An in vivo interfacial gene expression model combined with biomechanical analysis was used in order to determine the relationship between the molecular events taking place during osseointegration and the biomechanical stability of the implant. Anodically oxidized and machined, threaded titanium implants were characterized topographically, chemically and ultrastructurally. The implants were inserted in rat tibiae and the implant bone torsion stability was evaluated. After measurements, the implants were removed and analyzed with qPCR. Results showed an increase in the breakpoint torque of 140%, 170% and 190%, after 6, 14, and 28 days, respectively, at the oxidized implants as compared to the machined. Gene expression analysis revealed higher expression of runt related transcription factor-2 (Runx2) (after 28 d), osteocalcin (OC) and tartrate resistant acid phosphatase (TRAP) (after 6, 14 and 28 d) and cathepsin K (CATK) (after 6 and 14 d) at the oxidized implants. On the other hand, machined implants were associated with higher expression of tumor necrosis factor-α (TNF-α) (after 6 and 28 d) and interleukin-1β (IL-1β) (after 6, 14 and 28 d) compared to the oxidized implants. In conclusion, the favorable cellular and molecular events at the oxidized implants were in parallel with significantly stronger bone anchorage during osseointegration.
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| 10. |
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| 11. |
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| 12. |
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| 13. |
- Palmquist, Anders, 1977, et al.
(författare)
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A technique for evaluating bone ingrowth into 3D printed, porous Ti6Al4V implants accurately using X-ray micro-computed tomography and histomorphometry.
- 2017
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Ingår i: Micron. - : Elsevier BV. - 0968-4328. ; 94, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- This paper investigates the application of X-ray micro-computed tomography (micro-CT) to accurately evaluate bone formation within 3D printed, porous Ti6Al4V implants manufactured using Electron Beam Melting (EBM), retrieved after six months of healing in sheep femur and tibia. All samples were scanned twice (i.e., before and after resin embedding), using fast, low-resolution scans (Skyscan 1172; Bruker micro-CT, Kontich, Belgium), and were analysed by 2D and 3D morphometry. The main questions posed were: (i) Can low resolution, fast scans provide morphometric data of bone formed inside (and around) metal implants with a complex, open-pore architecture?, (ii) Can micro-CT be used to accurately quantify both the bone area (BA) and bone-implant contact (BIC)?, (iii) What degree of error is introduced in the quantitative data by varying the threshold values?, and (iv) Does resin embedding influence the accuracy of the analysis? To validate the accuracy of micro-CT measurements, each data set was correlated with a corresponding centrally cut histological section. The results show that quantitative histomorphometry corresponds strongly with 3D measurements made by micro-CT, where a high correlation exists between the two techniques for bone area/volume measurements around and inside the porous network. On the contrary, the direct bone-implant contact is challenging to estimate accurately or reproducibly. Large errors may be introduced in micro-CT measurements when segmentation is performed without calibrating the data set against a corresponding histological section. Generally, the bone area measurement is strongly influenced by the lower threshold limit, while the upper threshold limit has little or no effect. Resin embedding does not compromise the accuracy of micro-CT measurements, although there is a change in the contrast distributions and optimisation of the threshold ranges is required.
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| 14. |
- Palmquist, Anders, 1977, et al.
(författare)
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Acute Inflammatory Response to Laser-Induced Micro- and Nano-Sized Titanium Surface Features.
- 2013
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Ingår i: Clinical implant dentistry and related research. - : Wiley. - 1708-8208 .- 1523-0899. ; 15:1, s. 96-104
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Tidskriftsartikel (refereegranskat)abstract
- Background: The inflammatory process induced by implant surfaces is an important component of the tissue response, where limited knowledge is available regarding the role of surface topography. With laser ablation, a combined micro- and nanoscale surfacemodification could be created, which have been shown to enhance bone growth and biomechanical stability in vivo. Purpose: The aim of this article was to evaluate the early in vivo inflammatory response to laser-modified titanium disks, with machined titanium disks and sham operation sites serving as controls. Materials and Methods: Circular disks were installed in a subcutaneous rat model for 24 and 72 hours, where the cell number, cell types, and cytokine levels were evaluated. Results: The results revealed that significantly fewer inflammatory cells (mononuclear and polymorphonuclear) were attracted to the sites with the laser-modified implants compared with the machined titanium implants. Similar concentrations of pro-inflammatory cytokines (TNF-a and MCP-1), together with slightly higher cell viability, were observed around the laser-modified surface compared with the machined surface. Conclusions: The results in the present study suggest that the combination of surface micro and nano features of the laser-treated surface contributes to the downregulation of early inflammatory events.
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| 15. |
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| 16. |
- Rydén, Louise, 1975, et al.
(författare)
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Early inflammatory response in soft tissues induced by thin calcium phosphates.
- 2013
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Ingår i: Journal of biomedical materials research. Part A. - : Wiley. - 1552-4965 .- 1549-3296. ; 101A:9, s. 2712-2717
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Tidskriftsartikel (refereegranskat)abstract
- The inflammatory response to titanium and hydroxyapatite (HA)-coated titanium in living tissue is controlled by a number of humoral factors, of which monocyte chemoattractant protein-1 (MCP-1) has been specifically linked to the recruitment of monocytes. These cells subsequently mature into tissue-bound macrophages. Macrophages adhering to the proteins adsorbed at the implant surface play a pivotal role in initiating the rejection or integration of the foreign material. Despite this, little is known about the initial inflammatory events that occur in soft tissues following the implantation of titanium and HA-coated titanium implants. In this study, circular discs of commercially pure titanium (c.p. Ti) with either a thin crystalline HA coating or amorphous HA coating or uncoated were implanted subcutaneously into rats. The implants were retrieved after 24 and 72 h. The lactate dehydrogenase (LD) activity, DNA content, expression of MCP-1, interleukin-10 (IL-10), tumor necrosis factor α (TNF-α), as well as monocyte and polymorphonuclear granulocyte counts in the exudate surrounding the implants were analyzed. There were significantly higher DNA and LD levels around the titanium implants at 24 h compared with HA-coated titanium. A rapid decrease in MCP-1 levels was observed for all the implants over the period of observation. No statistically significant differences were found between the two HA-coated implants. Our results suggest a difference in the early soft-tissue response to HA-coated implants when compared with titanium implants, expressed as a downregulation of inflammatory cell recruitment. This suggests that thin HA coatings are promising surfaces for soft tissue applications.
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| 17. |
- Shah, Furqan A., et al.
(författare)
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Long-term osseointegration of 3D printed CoCr constructs with an interconnected open-pore architecture prepared by electron beam melting.
- 2016
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 36:May, s. 296-309
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Tidskriftsartikel (refereegranskat)abstract
- In orthopaedic surgery, cobalt chromium (CoCr) based alloys are used extensively for their high strength and wear properties, but with concerns over stress shielding and bone resorption due to the high stiffness of CoCr. The structural stiffness, principally related to the bulk and the elastic modulus of the material, may be lowered by appropriate design modifications, to reduce the stiffness mismatch between metal/alloy implants and the adjacent bone. Here, 3D printed CoCr and Ti6Al4V implants of similar macro-geometry and interconnected open-pore architecture prepared by electron beam melting (EBM) were evaluated following 26week implantation in adult sheep femora. Despite higher total bone-implant contact for Ti6Al4V (39±4%) than CoCr (27±4%), bone formation patterns were similar, e.g., densification around the implant, and gradual ingrowth into the porous network, with more bone in the outer half (periphery) than the inner half (centre). Raman spectroscopy revealed no major differences in mineral crystallinity, the apatite-to-collagen ratio, or the carbonate-to-phosphate ratio. Energy dispersive X-ray spectroscopy showed similar Ca/P ratio of the interfacial tissue adjacent to both materials. Osteocytes made direct contact with CoCr and Ti6Al4V. While osteocyte density and distribution in the new-formed bone were largely similar for the two alloys, higher osteocyte density was observed at the periphery of the porous network for CoCr, attributable to slower remodelling and a different biomechanical environment. The results demonstrate the possibility to achieve bone ingrowth into open-pore CoCr constructs, and attest to the potential for fabricating customised osseointegrated CoCr implants for load-bearing applications.
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| 18. |
- Silva, Ingrid, et al.
(författare)
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Quality of life in patients undergoing orthognathic surgery - A two-centered Swedish study
- 2016
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Ingår i: Journal of Cranio-Maxillofacial Surgery. - : Elsevier BV. - 1010-5182 .- 1878-4119. ; 44:8, s. 973-978
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Surgical corrections of dentofacial deformities have both physical and psychological impact on quality of life (QoL). The objectives of the present study were to evaluate the impact of oral health related problems on QoL before and after a combination of orthodontic treatment and orthognathic surgery. Additionally, the study aimed to identify correlations between different dentofacial patterns and possible improvements due to treatment. Material and methods: In a prospective study, we evaluated fifty patients before start of treatment, 6 weeks and 6 months postoperatively. The questionnaires used were: OHIP-14 (Short Form Oral Health Impact Profile), a condition-specific QOL approach (Orthognathic Quality of Life Questionnaires; OQLQ) and a social-demographic questionnaire. Results: There was a statistically significant improvement in the OHIP domains from baseline to 6 months follow-up and for the OQLQ the improvement was significant both at 6 weeks and 6 months in relation to the baseline data. Conclusion: Significant improvement of quality of life over time is proved by both OHIP-14 and OQLQ in the present study. Socio-demographic and holistic considerations are important when evaluating treatment outcome after combined orthodontic and orthognatic surgery. However, longer follow-up would be beneficial. (C) 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
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| 19. |
- Silva, Ingrid, et al.
(författare)
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Stability after maxillary segmentation for correction of anterior open bite: A cohort study of 33 cases.
- 2013
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Ingår i: Journal of Cranio-Maxillofacial Surgery. - : Elsevier BV. - 1010-5182 .- 1878-4119. ; 41:7
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this cohort study was to evaluate the stability after multi-segmentation of the maxilla for correction of anterior open bite deformities. A total of 33 patients who underwent segmented maxillary osteotomy between 1994 and 2006 were included in the study. Rigid fixation with plates and postsurgical intermaxillary fixation for 6 weeks was applied to each patient. All patients were then followed in a standardized examination procedure at months 6, 12, 18 and up to 30 months postoperatively. Vertical and horizontal relation of the incisors was measured both clinically and on cast models. The main finding was that statistically significant relapse was found vertically, whereas the horizontal relationship to the mandible was unchanged. The vertical relapses were predominantly seen in patients with severe open bite evident preoperatively.
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| 20. |
- Slotte, Christer, 1954, et al.
(författare)
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Gene Expression of Inflammation and Bone Healing in Peri-Implant Crevicular Fluid after Placement and Loading of Dental Implants. A Kinetic Clinical Pilot Study Using Quantitative Real-Time PCR.
- 2012
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Ingår i: Clinical implant dentistry and related research. - : Wiley. - 1708-8208 .- 1523-0899. ; 14:5, s. 723-736
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Early detection of healing complications after placement of dental implants is a pressing but elusive goal. This paper proposes a non-invasive diagnostic tool for monitoring healing- and peri-implant disease specific genes, complementary to clinical evaluations. Material and Methods: Eighteen partially edentulous patients were recruited to this pilot study. Three Brånemark TiUnite® implants/patient (Nobel Biocare) were placed in a one-stage procedure. Abutments with smooth or rough (TiUnite®) surface were placed. The test group (n=9) received fixed bridges (immediate loading), whereas the control group (n=9) implants were loaded 3 months after surgery. In addition to clinical measurements, crevicular fluid was collected using paper strips at the implant abutments 2, 14, 28, and 90 days postoperative. mRNA was extracted, purified, and converted to cDNA. Quantitative PCR assays for IL-1β, TNF-α, Osteocalcin (OC), Alkaline Phosphatase (ALP), Cathepsin K, Tartrate Resistant Acid Phosphatase, and 18S ribosomal RNA were designed and validated. Relative gene expression levels were calculated. Results: One implant was lost in the control group and three in the test group. In one test patient, one implant showed lowered stability after 2 to 4 weeks and was unloaded. Later implant stability improved which allowed for loading after 3 to 4 months. TNF-α and ALP most commonly showed correlation with clinical parameters followed by IL-1β and OC. The strongest correlation was found for TNF-α with clinical complications at 2 and 14 days (p=.01/r=-048, and p=.0004/r=-0.56, respectively; test and control groups together). In some cases, gene expression predicted clinical complications (TNF-α, ALP, CK). Conclusion: This study is based on samples from few individuals; still, some genes showed correlation with clinical findings. Further studies are needed to refine and optimize the sampling process, to find the appropriate panel, and to validate gene expression for monitoring implant healing.
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| 21. |
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| 22. |
- Stenlund, Patrik, et al.
(författare)
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Osseointegration Enhancement by Zr doping of Co-Cr-Mo Implants Fabricated by Electron Beam Melting
- 2015
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Ingår i: Additive Manufacturing. - : Elsevier BV. - 2214-8604 .- 2214-7810. ; 6, s. 6-15
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Tidskriftsartikel (refereegranskat)abstract
- Direct osseous healing to prosthetic components is a prerequisite for the clinical success of uncemented treatment in total hip replacements (THR). The demands imposed on the material properties are constantly being stepped up to withstand the impact of an active lifestyle and ensure lifelong integration. Cobalt–chromium–molybdenum (Co-Cr-Mo) materials are interesting for their excellent mechanical stability, corrosion resistance and possibility to be produced by additive manufacturing into complex designs with modifiable stiffness. The bone response to Co-Cr-Mo is regarded as inferior to that of titanium and are usually cemented in THR. The hypothesis in the present study was that a low amount of Zr in the Co-Cr-Mo alloy would improve the bone response and biomechanical anchorage. The results showed significantly higher implant stability for the Co-Cr-Mo alloy with an addition of 0.04% Zr after eight weeks of healing in rabbits, while no major differences were observed in the amount of bone formed around the implants. Further, bone tissue grew into surface irregularities and in direct contact with the implant surfaces. It is concluded that additively manufactured Co-Cr-Mo alloy implants osseointegrate and that the addition of a low amount of Zr to the bulk Co-Cr-Mo further improves the bone anchorage.
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| 23. |
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| 24. |
- Suska, Felicia, 1974, et al.
(författare)
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Electron Beam Melting Manufacturing Technology for Individually Manufactured Jaw Prosthesis: A Case Report
- 2016
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Ingår i: Journal of Oral and Maxillofacial Surgery. - : Elsevier BV. - 0278-2391 .- 1531-5053. ; 74:8
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Tidskriftsartikel (refereegranskat)abstract
- In the field of maxillofacial reconstruction, additive manufacturing technologies, specifically electron beam melting (EBM), offer clinicians the potential for patient-customized design of jaw prostheses, which match both load-bearing and esthetic demands. The technique allows an innovative, functional design, combining integrated porous regions for bone ingrowth and secondary biological fixation with solid load-bearing regions ensuring the biomechanical performance. A patient-specific mandibular prosthesis manufactured using EBM was successfully used to reconstruct a patient's mandibular defect after en bloc resection. Over a 9-month follow-up period, the patient had no complications. A short operating time, good esthetic outcome, and high level of patient satisfaction as measured by quality-of-life questionnaires-the European Organisation for Research and Treatment of Cancer QLQ-C30 (30-item quality-of-life core questionnaire) and H&N35 (head and neck cancer module)-were reported for this case. Individually planned and designed EBM-produced prostheses may be suggested as a possible future alternative to fibular grafts or other reconstructive methods. However, the role of porosity, the role of geometry, and the optimal combination of solid and porous parts, as well as surface properties in relation to soft tissues, should be carefully evaluated in long-term clinical trials. (C) 2016 American Association of Oral and Maxillofacial Surgeons
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| 25. |
- Suska, Felicia, 1974, et al.
(författare)
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Enhancement of CRF-PEEK osseointegration by plasma-sprayed hydroxyapatite: A rabbit model.
- 2014
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Ingår i: Journal of biomaterials applications. - : SAGE Publications. - 1530-8022 .- 0885-3282. ; 29:2, s. 234-242
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Tidskriftsartikel (refereegranskat)abstract
- Carbon-fibre-reinforced polyether ether ketone (CFR-PEEK) exhibits excellent biomechanical properties as it has an elastic modulus similar to bone. However, CFR-PEEK displays inferior biocompatibility compared with titanium alloy and coating techniques are therefore of interest in order to improve integration. In this paper, the early biological response to CFR-PEEK implants, with and without hydroxyapatite coating, was investigated. Furthermore, a hydroxyapatite-coated titanium alloy reference served as a clinically relevant control. The study was conducted in a rabbit model, both in femur trabecular bone as well as in tibia cortical bone. The results demonstrated that an hydroxyapatite coating significantly enhances the bone response to PEEK implants invivo. Moreover, in cortical bone, hydroxyapatite-coated PEEK implants induced superior bone response compared with hydroxyapatite-coated Ti ones. These results suggest that hydroxyapatite-coated CFR-PEEK is a suitable material for invivo implantation.
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| 26. |
- Suska, Felicia, 1974, et al.
(författare)
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Fibrous capsule formation around titanium and copper.
- 2008
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Ingår i: Journal of Biomedical Materials Research Part A. - : Wiley. - 1549-3296 .- 1552-4965 .- 0021-9304 .- 1097-4636. ; 85:4, s. 888-96
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies suggest that implant material properties influence the quality and quantity of fibrous capsule around the implant. However, the precise relation between material surface chemistry, early inflammatory response, and fibrous subsequent repair outcome is still unknown. Titanium (Ti) and copper (Cu), surfaces with different inflammatory potential, were implanted subcutaneously in rats and retrieved fibrous capsules were analyzed after 28 and 56 days. Histological examinations show pronounced differences in capsule morphology. The fibrous capsule around Ti was thinner than that around Cu, with less number of the inflammatory cells in the layer close to the implant surface, and less and smaller blood vessels. The capsule around Cu was thick, with a large number of the inflammatory cells, particularly macrophages and giant cells, and increased number of blood vessels. Our study suggests that material surface properties, which initiate early, multiple cellular inflammatory events, are also associated with increased fibrosis and angiogenesis during repair phase. (c) 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007.
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| 27. |
- Suska, Felicia, 1974, et al.
(författare)
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In vivo cytokine secretion and NF-kappaB activation around titanium and copper implants.
- 2005
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 26:5, s. 519-27
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Tidskriftsartikel (refereegranskat)abstract
- The early biological response at titanium (Ti), copper (Cu)-coated Ti and sham sites was evaluated in an in vivo rat model. Material surface chemical and topographical properties were characterized using Auger electron spectroscopy, energy dispersive X-ray spectroscopy and interferometry, respectively. The number of leukocytes, cell types and cell viability (release of lactate dehydrogenase) were determined in the implant-interface exudate. The contents of activated nuclear transcription factor NF-kappaB, interleukin-6 (IL-6) and interleukin-10 (IL-10) were determined by enzyme linked immunosorbent assay. An increase in the number of leukocytes, in particular, polymorphonuclear leukocytes, was observed between 12 and 48 h around Cu. A marked decrease of exudate cell viability was found around Cu after 48 h. The total amounts of activated NF-kappaB after 12 h was highest in Ti exudates whereas after 48 h the highest amount of NF-kappaB was detected around Cu. The levels of cytokine IL-6 were consistently high around Cu at both time periods. No differences in IL-10 contents were detected, irrespective of material/sham and time. The results show that materials with different toxicity grades (titanium with low and copper with high toxicity) exhibit early differences in the activation of NF-kappaB, extracellular expression and secretion of mediators, causing major differences in inflammatory cell accumulation and death in vivo.
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| 28. |
- Suska, Felicia, 1974, et al.
(författare)
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In vivo evaluation of noble metal coatings
- 2010
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Ingår i: Journal of Biomedical Materials Research Part B: Applied Biomaterials. - 1552-4981. ; 92B:1, s. 86-94
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Tidskriftsartikel (refereegranskat)abstract
- A nanotopographic noble metal (Ag, Au, Pd) coating has been applied on commercial urinary catheters and used in more than 80,000 patients, with good clinical results. We have previously evaluated the biocompatibility of different variations of this coating, showing high cellular viability and function in vitro. However, the reasons for good clinical and preclinical behavior are not known. This in vivo study aimed to investigate the soft tissue peri-implant reaction to five coatings with systematically altered noble metal ratios after 1, 3, and 21 days of implantation in rats. The results show that coatings of silver only, or silver with medium amounts of gold and low-medium palladium content were superior to other tested coatings. Such surfaces were during the first days after implantation associated with a decreased recruitment of inflammatory cells to implant close exudates, a lower percentage of neutrophils, higher cell viability, and lower production of monocyte chemoattractant protein-1 (MCP-1), compared to the other coatings and uncoated silicone (PDMS) control. In contrast, the addition of higher concentrations of gold and palladium to silver induced a thicker soft tissue capsule. Coatings with high concentration of palladium induced the thickest fibrouscapsule after 21 days of implantation. The study demonstrates that by varying the noble metal ratio at implant surfaces it is possible to modulate inflammation and fibrosis in soft tissue.
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| 29. |
- Suska, Felicia, 1974, et al.
(författare)
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In vivo/ex vivo cellular interactions with titanium and copper.
- 2001
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Ingår i: Journal of materials science. Materials in medicine. - 0957-4530 .- 1573-4838. ; 12:10-12, s. 939-44
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Tidskriftsartikel (refereegranskat)abstract
- Machined, commercially pure titanium (Ti) disks were coated with approximately 400 nm copper (Cu) by physical vapor deposition or left uncoated. The kinetics of inflammatory cell recruitment, distribution and viability was evaluated around Ti, Cu, and in sham sites after 1, 3, 12, 18, 24, and 48 h in a rat subcutaneous (s.c.) model. Further analysis of the cells on implant surfaces was performed by ex vivo incubation of the disks. Ti and Cu stimulated an increased recruitment of inflammatory cells in comparison with sham sites. A markedly higher amount of cells, predominantly polymorpho-nuclear granulocytes (PMN), was detected around Cu after 18 h and onwards. More cells were found at the implant surfaces than in the surrounding exudates after 18 h. The total amount of lactate dehydrogenase (LDH), an indicator of plasma membrane injury, was higher in Cu exudates after 18 h in comparison with Ti and sham. In contrast, no differences in the proportion of dead cells (trypan blue dye uptake) were detected in the exudates. Further, LDH levels were higher around Ti than Cu during the initial 18 h of ex vivo incubation. The results of this study indicate that the early inflammatory process associated with a cytotoxic material in soft tissues is largely attributed to the induction of a markedly strong and prolonged chemotactic response. In contrast, this process is characterized by a higher amount of inflammatory cells around a biocompatible material than in sham sites, but with a transient course and total LDH similar to sham sites.
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| 30. |
- Suska, Felicia, 1974, et al.
(författare)
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Monocyte viability on titanium and copper coated titanium.
- 2005
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 26:30, s. 5942-50
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Tidskriftsartikel (refereegranskat)abstract
- The role of apoptosis/cell death in the inflammatory response at the implanted materials is unexplored. Two surfaces with different cytotoxic potential and in vivo outcomes, titanium (Ti) and copper (Cu) were incubated in vitro with human monocytes and studied using a method to discriminate apoptotic and necrotic cells (Annexin V/PI staining). Further, staurosporine, a potent inducer of apoptosis, was added to the surface adherent monocytes. Lactate dehydrogenase (a marker of cell membrane injury) and TNF-alpha and IL-10, cytokines, previously suggested to play a major role in the monocyte apoptosis, were assayed in the culture medium. The results demonstrated that Ti surfaces displayed enhanced monocyte survival and production of IL-10 and TNF-alpha. Cu adherent cells exhibited apoptotic signs as early as 1h after incubation. In contrast to Ti, after 48 h the predominance of apoptotic cells switched to apoptotic/necrotic cells on Cu surfaces. Staurosporine treatment of Ti adherent cells mediated similar type of cell death. LDH and cytokine contents were low around Cu surfaces, partly explained by interference between Cu ions and LDH and cytokines. This study suggests that material properties rapidly influence the onset of human monocyte apoptosis and progression to late apoptosis/necrosis. Early detection of apoptosis and cell death may be important for the understanding of the biological response to implanted materials.
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| 31. |
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| 32. |
- Suska, Felicia, 1974
(författare)
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On the initial inflammatory response to variations in biomaterial surface chemistry.
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aims. The aim of the present thesis was, firstly, to develop in vivo and ex vivo models for analysis of peri-implant exudate and implant adherent cells and, secondly, to characterize the early inflammatory response to materials with different surface chemical functionalization as well as materials with inert (Ti) and cytotoxic (Cu) properties.Materials and Methods. C. p. titanium (Ti) disks were evaporated with gold (Au) or copper (Cu). Au surfaces were functionalized with alkane thiols. Pure Au, Au functionalized with -OH (hydrophilic) or -CH3 (hydrophobic) groups represent material surfaces with small chemical alterations, whereas c. p. Ti and Cu surfaces represent material surface with major variations in chemistry. Surfaces were implanted subcutaneously in rats for time periods ranging between 1 h and 48 h. Early inflammatory events (inflammatory cell recruitment, distribution, activation of transcription factor NF-kappaB, cytokine production, and cell death) and fibrous capsule formation (28 d) were evaluated. Further, surfaces with adherent cells were incubated ex vivo and implant adherent cells were characterized with respect to oxidative burst, cytokine secretion and cells damage (lactate dehydrogenase, LDH, content). Mechanisms of Ti and Cu induced cell death were analysed in vitro upon incubation of human peripheral blood mononuclear cells (PBMC) with different material surfaces.Results. An experimental rat model was developed, enabling the analysis of implant adherent cells ex vivo. The kinetics of cytokine secretion by implant adherent cells ex vivo was similar to that detected in vivo, indicating that cells associated with the material surface contributed substantially to the total inflammatory response.Distinct chemical functionalization of material surfaces influenced cellular distribution and oxidative burst during in vivo implantation. Methylated, hydrophobic surfaces were associated with a greater proportion of exudate-located cells than hydroxylated and gold surfaces. Cells associated with hydroxylated, hydrophilic surfaces responded with a relatively higher chemiluminescence after PMA stimulation.Major variations in surface chemistry (Ti and Cu) influenced cell recruitment, the type of recruited cell, cytokine production, kinetics of cell death, intracellular signalling and fibrous capsule organisation: Ti was associated with a high and transient leukotactic reponse, predominance of mononuclear cells, high and transient amounts of active NF-kappaB in exudates cells and an early and transient cytokine production (IL-1alpha, TNF-alpha and IL-6) in vivo. The fibrous capsule around Ti was thinner than around Cu. In vitro, high cellular viability and activity were characteristic features of human monocytes cultured on Ti. Cu was associated with a delayed but extended leukotactic response, high degree of cellular damage, predominance of PMN in the inflammatory exudates, and delayed and high amounts of transcriptional factor NF-kappaB and pro-inflammatory cytokines IL-1alpha, TNF-alpha and IL-6 in vivo. The fibrous capsule around Cu was thicker than around Ti and was characterized by accumulation of inflammatory cells close to the implant surface. Further, Cu implants induced rapid cellular death, probably through apoptosis, in vitro. Conclusions. The present experimental results show that material surface chemical functionality influences specific events in the inflammatory response, including cell distribution and respiratory burst, whereas cytokine secretion seemed not to be affected. It is therefore possible, at least partly, to govern in vivo reactions through tailor-made modifications of material surface chemistry.The present experimental results show that material surface alterations, which induce cell death also initiate early, multiple cellular and inflammatory processes which in turn are related to the subsequent repair phase. Some of these processes may be determined in the present experimental system, thus providing a pre-clinical screening of materials with adverse effects.The early and high inflammatory response around Ti contradicts the prevailing view of Ti being an inert material. It is suggested that the observed transient biologic response is of importance for the understanding of the mechanisms of tissue integration and biocompatibility.
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| 33. |
- Svensson, Sara, 1981, et al.
(författare)
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A novel soft tissue model for biomaterial-associated infection and inflammation - Bacteriological, morphological and molecular observations
- 2015
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Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 41, s. 106-121
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Tidskriftsartikel (refereegranskat)abstract
- Infection constitutes a major risk for implant failure, but the reasons why biomaterial sites are more vulnerable than normal tissue are not fully elucidated. In this study, a soft tissue infection model was developed, allowing the analysis of cellular and molecular responses in each of the sub-compartments of the implant-tissue interface (on the implant surface, in the surrounding exudate and in the tissue). Smooth and nanostructured titanium disks with or without noble metal chemistry (silver, gold, palladium), and sham sites, were inoculated with Staphylococcus epidermidis and analysed with respect to number of viable bacteria, number, viability and gene expression of host cells, and using different morphological techniques after 4 h, 24 h and 72 h. Non-infected rats were controls. Results showed a transient inflammatory response at control sites, whereas bacterial administration resulted in higher recruitment of inflammatory cells (mainly polymorphonuclear), higher, continuous cell death and higher gene expression of tumour necrosis factor-alpha, interleukin-6, interleukin-8, Toll-like receptor 2 and elastase. At all time points, S. epidermidis was predominantly located in the interface zone, extra- and intracellularly, and lower levels were detected on the implants compared with surrounding exudate. This model allows detailed analysis of early events in inflammation and infection associated to biomaterials in vivo leading to insights into host defence mechanisms in biomaterial-associated infections.
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| 34. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Svensson, Sara, 1981, et al.
(författare)
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Osseointegration of titanium with an antimicrobial nanostructured noble metal coating
- 2013
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Ingår i: Nanomedicine: Nanotechnology, Biology, and Medicine. - : Elsevier BV. - 1549-9634 .- 1549-9642. ; 9:7, s. 1048-1056
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Tidskriftsartikel (refereegranskat)abstract
- Nanometer scale surface features on implants and prostheses can potentially be used to enhance osseointegration and may also add further functionalities, such as infection resistance, to the implant. In this study, a nanostructured noble metal coating consisting of palladium, gold and silver, never previously used in bone applications, was applied to machined titanium screws to evaluate osseointegration after 6 and 12. weeks in rabbit tibiae and femurs. Infection resistance was confirmed by in vitro adhesion test. A qualitatively and quantitatively similar in vivo bone response was observed for the coated and uncoated control screws, using histology, histomorphometry and electron microscopy. The bone-implant interface analysis revealed an extensive bone formation and direct bone-implant contact. These results demonstrate that the nanostructured noble metal coating with antimicrobial properties promotes osseointegration and may therefore be used to add extra implant functionality in the form of increased resistance to infection without the use of antibiotics. From the Clinical Editor: The authors of this paper demonstrate that nanostructured noble metal coating of implants and prostheses used in orthopedic procedures promotes osseointegration and may be used to add extra implant functionality in the form of increased resistance to infection without the use of antibiotics.
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| 41. |
- Thomsen, Peter, 1953, et al.
(författare)
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Preclinical in vivo models to study the inflammatory response to implants.
- 2006
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Ingår i: Abstract, Invited lecture, CIMTEC, Italy.
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Konferensbidrag (refereegranskat)abstract
- The interactions between the material surface and cellular and molecular components in the interface tissue are key features in the selection of optimal materials for clinical use. A quantitative analysis of the inflammatory, reparative and regenerative processes which occur as a response to implant modifications is therefore required. A prerequisite for such analyses is the development of experimental models which allow an access to sampling and harvesting of interfacial molecules, cells and tissues for subsequent analyses. The lecture will provide an overview of the features of such models and examples from own studies where biochemical, immunological and morphological techniques may be combined. We have developed a simple, reproducible experimental model in vivo, allowing a detailed analysis of initial inflammatory events as well as later, reparative processes in association with implant surfaces. Studies on the role of material bulk and surface properties for inflammatory cell chemotaxis, viability and cytokine patterns around materials will be discussed using metals, polymers, bioceramics and surface functionalizations.
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| 42. |
- Wermelin, Karin, 1977-, et al.
(författare)
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Stainless steel screws coated with bisphosphonates gave stronger fixation and more surrounding bone. Histomorphometry in rats.
- 2008
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 42:2, s. 365-71
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Tidskriftsartikel (refereegranskat)abstract
- Coating of stainless steel screws with bisphosphonate in a fibrinogen matrix leads to an enhancement of the pullout strength 2 weeks after insertion in rat tibiae. This effect then increases over time until at least 8 weeks. The pullout force reflects the mechanical properties of the bone within the threads, which acts as a screw nut. The aim of the present study was to find descriptive and morphometric histological correlates to the increased pullout strength. Because the bisphosphonates are applied via the implant surface, we also measured bone to implant contact and how far away from the surface any effects could be seen. Stainless steel screws underwent one of three treatments: uncoated control, controls coated with a layer of cross-linked fibrinogen, or screws further modified with bisphosphonates covalently linked and physically adsorbed to the fibrinogen layer. At 1 (n=33) and 8 (n=27) weeks, bone to implant contact and bone area density in the threads were measured, as well as bone area density at 250 and 500 microm from the outer edge of the threads. Additionally, removal torque for each screw treatment was measured at 2 weeks (n=28). At 8 weeks, the part of the bisphosphonate screw that was located in the marrow cavity had become surrounded with bone, whereas there was almost no bone surrounding the controls. The bone area density in the threads along the entire bisphosphonate screw was increased by 40% compared with uncoated controls, and at 250 microm distance it was more than doubled. At 1 week, coated screws had less implant-bone contact, but at 8 weeks there was no difference between uncoated and bisphosphonate-coated screws. The bisphosphonate screws had 50% increased removal torque at 2 weeks compared to uncoated screws. Howship's lacunae and osteoclasts were found near the screws with bisphosphonates at 8 weeks, suggesting that some bone remodeling took place near the implant, in spite of the presence of bisphosphonates.
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| 43. |
- Xia, Wei, et al.
(författare)
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Bioactive Spheres: The Way of Treating Dentin Hypersensitivity
- 2016
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Ingår i: Acs Biomaterials-Science & Engineering. - : American Chemical Society (ACS). - 2373-9878. ; 2:5, s. 734-740
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Tidskriftsartikel (refereegranskat)abstract
- Sealing exposed dental tubules is the most effective and long-term way to relieve the pain induced by dental sensitivity. A bioactive hollow sphere (strontium substituted calcium phosphate) was synthesized and added in toothpaste to study its effect on dental hypersensitivity via tooth tubules occlusion and mineralization. The size of spheres is perfect for penetrating into dental tubules, reaching to 20 pm into the tubules. The exposed dental tubules were occluded by spheres and new apatite layer after 3 days brushing. The spheres attached to the surface of dentin and the mineralized surface contained two layers, a porous layer followed by a dense apatite layer. The porous layer can be dissolved in an acidic solution, but the following dense layer could be kept even after soaking in an acid solution. In conclusion, Sr-substituted calcium phosphate spheres could be a good candidate for at-home treatment of dental hypersensitivity.
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| 44. |
- Zoric, Neven, et al.
(författare)
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Quantitative PCR: A promising technique investigating the early bone-implant interface
- 2007
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Ingår i: Abstract, European Association for Osseointegration (EAO), 16th Annual Scientific Meeting, Barcelona, Spain. ; 25-27 October
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Konferensbidrag (refereegranskat)abstract
- Objectives: Studies on the early tissue response to materials are difficult due to the inaccessibility of the interface zone and lack of sensitive techniques. The purpose of the present study was to apply quantitative PCR (qPCR) in combination with LM and SEM for the evaluation of early gene expression response as well as cellular reactions close to titanium implants. Experimental methods: Anodically oxidized titanium (TiUniteTM; Nobel Biocare AB) and machined titanium implants (2mm×2mm) were inserted in the rat tibia. After 1,3, and 6 days, implants were unscrewed and surrounding bone was retrieved. Both the implants and bone were analyzed with qPCR, routine histology and SEM. The amount of mRNA was normalized to 18S protein subunit. Results: After the initial inflammatory response, the tissue located inside the threads became rapidly organized. SEM analysis showed mesenchymal-like cells extending their processes into the pores of the anodically oxidized surface. qPCR demonstrated significantly higher 18S around anodically oxidized screws and in the surrounding tissues. Alkaline phosphatase (osteoblast marker), TRAP and Cathepsin K (osteoclast markers) mRNA, but not the inflammatory markers (TNF-alpha and IL-1beta) were expressed at different levels around the two surfaces. Conclusions: The results demonstrate that the experimental model and qPCR provide interesting possibilities to analyze the mechanisms of osseointegration. Furthermore, remodelling and in particular the molecular processes occur at implant surfaces in vivo already 3 days after implantation. Support: Swedish Research Council and the Institute for Biomaterials and Cell Therapy, Göteborg, Sweden
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| 45. |
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