| 1. |
- Ben Amara, Heithem, 1984, et al.
(författare)
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Immunomodulation by biodegradable Mg-implants promotes soft and hard tissues responses in vivo
- 2023
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Ingår i: Scandinavian Society of Biomaterials conference, 21–24 March 2023, Røros, Norway.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION: Magnesium (Mg)-based degradable implants are an attractive treatment solution for musculoskeletal injuries, avoiding second-stage surgical removal. In multiple clinical applications, the implant is in contact with both the bone and the overlying soft tissue. Although Mg implants are often presented to hold anti-inflammatory properties, less attention has been paid to the sequential response to these implants including initial immune response and subsequent tissue repair. The present study investigated the molecular, cellular, and structural events taking place at the Mg implant interface to soft tissue and bone after in vivo implantation in dedicated experimental rat models. METHODS: Male Sprague Dawley rats received disc-shaped implants in the dorsum subcutis or screw-shaped implants in the proximal tibial metaphysis. Implants were manufactured from pure magnesium (99.99% - high purity; Mg) or from pure titanium (grade 4; Ti) as control. Animals were euthanized after 1, 3, 6, 14, and 28 day of soft tissue implantation, and after 3 and 28 days of bone implantation. Two types of samples were collected: 1-Implants with the adherent cells (n=7-8/group/time-point). These were allocated for cell counting and /or gene expression analyses of implant-adherent cells. 2-Peri-implant tissue with implants (n = 8/group/time-point). These enabled histological and histomorphometric analyses of the fibrous capsule organization around implants inserted in soft tissues and of osseointegration parameters at the bone-implant interface. Statistical comparisons between experimental groups were run using Kruskal-Wallis, and Mann-Whitney tests (p<0.05). RESULTS: Cells adherent to the surface of the implants featured different gene regulation patterns between Mg and Ti groups (Fig. 1). Consistently in soft tissue and in bone, macrophage polarization markers indicated higher expression of proinflammatory macrophage gene inducible nitric oxide synthase (iNos) initially at Mg versus Ti (3 d in bone and 1-6 d in soft tissue). Afterward, gene expression of both macrophage subtypes markers (proinflammatory – iNos and prohealing – Mannose receptor c1; Mrc1) was comparable between implants, irrespective of their insertion site. Histomorphometry evidenced superior bone-implant contact (at 28 d in bone) and thinner fibrous capsule (at 6-28 d in soft tissue) for Mg versus Ti. CONCLUSIONS: In comparison to non-degradable Ti, both soft tissue and bone responses to biodegradable Mg featured an initial yet transient gene activation of the macrophage proinflammatory subtype. Such immunomodulation by Mg resulted in the reduction of fibrous encapsulation in soft tissue and in the promotion of bone formation at the bone-implant interface. ACKNOWLEDGEMENTS: Mg implants were generously provided by Helmholtz-Zentrum Hereon, Geesthacht, Germany. This project is part of the European Training Network within the framework of Horizon 2020 Marie Skłodowska-Curie Action No 811226.
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| 2. |
- Ben Amara, Heithem, 1984, et al.
(författare)
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In vivo interaction between biodegradable magnesium implants and soft tissue Part II: Kinetics of the cellular response at the host-implant interface
- 2021
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Ingår i: 13th Biometal Conference, 23-26 August 2021, Virtual Conference..
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION: Regenerative therapies often engage multiple tissues. Soft tissue complications (e.g. dehiscences and infection) may violate successful bone regeneration. Magnesium (Mg)-based degradable implants is a promising treatment alternative for musculoskeletal injuries, avoiding second-stage surgical removal. In several clinical applications, the implant is in contact with both the bone and the overlying soft tissue. Whereas the bone response to Mg implants has been a major research focus, less attention has been paid to the soft tissue response. The present study investigated the spatial and temporal molecular, cellular and structural events taking place at the soft tissue-Mg implant interface after in vivo implantation in an experimental rat model. METHODS: Following approval by the Local Ethical Committee at the University of Gothenburg (Dnr 02437/2018), female Sprague-Dawley rats (n=90) were implanted with discs manufactured from pure magnesium (99.99% - high purity; Mg) or from pure titanium (grade 4; Ti) (herein, employed as a control, possessing biocompatibility properties). Subcutaneous pockets were surgically created in the animal dorsum and were implanted with: 1- Ti; or 2- Mg discs; or 3- left without implants (Sham Ti or Sham Mg). After 1, 3, 6, 14 and 28 days, animals were euthanized, and three types of samples were retrieved: 1-Implants with the adherent cells (n=8/group/time-point): for cell counting and molecular gene expression of the implant-adherent cells. 2-Peri-implant exudate (n=8/group/time-point): for analyses of the number, type, viability, and gene expression of cells in the peri-implant space. 3-Peri-implant tissue with implants (n=8/group/time-point): enabling histological and histomorphometric analyses of soft tissue and fibrous capsule organization around the implant. Statistical comparisons were made between experimental groups at each time point and between time-points for each experimental group. (Kruskal-Wallis, Mann-Whitney and Wilcoxon signed-rank tests; p<0.05). RESULTS: Cells recruited to the exudates and adherent to the surface of the implants featured different kinetics between Mg and Ti groups. At the surface of Mg implant, the number of adherent cells sharply increased from 1 day to reach a peak at 6 days, thereafter decreasing toward 28 days. The ratio of implant-adherent/exudate cells was significantly higher at Mg vs Ti after 6 days, whereas the reverse was detected after 28 days. RNA extracted from cells from the different compartments revealed good quality, allowing detailed molecular analysis. After 28d, the fibrous capsule around Mg implants was significantly thinner than around Ti. CONCLUSIONS: In comparison to non-degradable Ti controls, soft tissue healing around biodegradable Mg implants is characterized by an early, intense, but yet transient, cellular influx in the immediate vicinity of the implant surface, and, at later stage, with a reduced fibrotic encapsulation. ACKNOWLEDGEMENTS: Mg implants were generously provided by the Helmholtz-Zentrum Hereon, Geesthacht, Germany. This project is part of the European Training Network within the framework of Horizon 2020 Marie Skodowska-Curie Action No 811226.
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| 3. |
- Ben Amara, Heithem, 1984, et al.
(författare)
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Magnesium implant degradation provides immunomodulatory and proangiogenic effects and attenuates peri-implant fibrosis in soft tissues
- 2023
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Ingår i: Bioactive Materials. - : Elsevier BV. - 2452-199X. ; 26, s. 353-369
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Tidskriftsartikel (refereegranskat)abstract
- Implants made of magnesium (Mg) are increasingly employed in patients to achieve osteosynthesis while degrading in situ. Since Mg implants and Mg2+ have been suggested to possess anti-inflammatory properties, the clinically observed soft tissue inflammation around Mg implants is enigmatic. Here, using a rat soft tissue model and a 1-28 d observation period, we determined the temporo-spatial cell distribution and behavior in relation to sequential changes of pure Mg implant surface properties and Mg2+ release. Compared to nondegradable titanium (Ti) implants, Mg degradation exacerbated initial inflammation. Release of Mg degradation products at the tissue-implant interface, culminating at 3 d, actively initiated chemotaxis and upregulated mRNA and protein immunomodulatory markers, particularly inducible nitric oxide synthase and toll-like receptor-4 up to 6 d, yet without a cytotoxic effect. Increased vascularization was demonstrated morphologically, preceded by high expression of vascular endothelial growth factor. The transition to appropriate tissue repair coincided with implant surface enrichment of Ca and P and reduced peri-implant Mg2+ concentration. Mg implants revealed a thinner fibrous encapsulation compared with Ti. The detailed understanding of the relationship between Mg material properties and the spatial and time-resolved cellular processes provides a basis for the interpretation of clinical observations and future tailoring of Mg implants.
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| 4. |
- Ben Amara, Heithem, 1984, et al.
(författare)
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Promoting soft and hard tissue repair via immunomodulation by the surface degradation of magnesium implants in vivo
- 2023
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Ingår i: Materials for Tomorrow conference by Chalmers University of Technology, 8-10 November 2023, Gothenburg, Sweden.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- INTRODUCTION: Magnesium (Mg) is a reactive metallic biomaterial that degrades via surface corrosion upon contact with body fluids. By virtue of its degradation and mechanical properties, Mg implants are currently employed with success to treat musculoskeletal injuries and avoid second-stage surgical removal 1. While these implants are claimed to possess anti-inflammatory properties, this notion contrasts with the initial signs of inflammation observed in the soft tissue of patients treated with Mg implants. This study investigated how the surface degradation of Mg implants in vivo influences the molecular, cellular, and structural events during initial inflammation and subsequent healing of the interfacing soft tissue and bone in comparison to nondegradable titanium (Ti) implants using experimental rat models. METHODS: Rats received disc-shaped implants in their dorsum subcutis or screw-shaped implants in the proximal metaphysis of their tibiae. Implants were manufactured from pure Mg (>99.995% - high purity) or from pure Ti (grade 4). Animals were euthanized after 1, 3, 6, 14, and 28 days of soft tissue implantation, and after 3 and 28 days of bone implantation. Two types of samples were collected: i) Implants only (n = 7-8/group/time-point): for counting and/or gene expression analyses of implant-adherent cells. ii) Implants with peri-implant tissues (n = 5-8/group/time-point): for compositional analysis of the Mg degradation layer in conjunction with the histomorphometry of the fibrous capsule around implants in soft tissues and of osseointegration at the bone–implant interface. Statistical comparisons were run using Kruskal-Wallis and Mann-Whitney tests (p<0.05). RESULTS: Cells adherent to the implant surfaces featured different gene regulation patterns between Mg and Ti groups (Fig. 1). Initially in soft tissue (1–6 d) and bone (3 d), a higher expression of proinflammatory macrophage polarization markers, e.g. inducible nitric oxide synthase (iNos), was shown in Mg versus Ti groups. Afterward, by 28 d, gene expression of both macrophage subtype markers (proinflammatory – iNos, and prohealing – Mannose receptor c1; Mrc1) was comparable between implants, irrespective of their insertion site. Histomorphometry revealed superior bone–implant contact (at 28 d in bone) and thinner fibrous capsule (at 6–28 d in soft tissue) for Mg versus Ti (Fig. 1). The 28 d-degradation layer at the Mg surface was enriched in Ca and P in both soft tissue and bone. CONCLUSIONS: In comparison to Ti implants, both soft tissue and bone responses to Mg implants featured an initial, amplified, yet transient, inflammation marked by the gene activation of the macrophage proinflammatory subtype. Such immunomodulation by the surface degradation of Mg implant promoted more bone deposition, at the bone–implant interface, and less fibrous encapsulation, at the soft tissue–implant interface. REFERENCES: 1. Han et al. Mater Today 2019, 23: 57-71. ACKNOWLEDGEMENTS: Horizon 2020 Marie Skłodowska-Curie Action (No 811226) and Area of Advance Materials/Chalmers and GU Biomaterials. Mg implants were generously provided by Hereon, Geesthacht, Germany.
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| 5. |
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| 6. |
- Cardemil, Carina, et al.
(författare)
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Strontium-doped calcium phosphate and hydroxyapatite granules promote different inflammatory and bone remodelling responses in normal and ovariectomised rats.
- 2013
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Ingår i: PLosOne. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-α (TNF-α), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone.
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| 7. |
- Cardemil, Carina, et al.
(författare)
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The effects of a systemic single dose of zoledronic acid on post-implantation bone remodelling and inflammation in an ovariectomised rat model.
- 2013
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Ingår i: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 34:5, s. 1546-61
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Tidskriftsartikel (refereegranskat)abstract
- Bisphosphonates reverse the negative effects of ovariectomy on bone, but they have also been associated with adverse processes in human jawbone. The molecular events determining bone regeneration and implant integration in osteoporotic conditions, with and without bisphosphonate treatment, are unclear. In this study, ovariectomised rats, to which a single dose of saline (NaCl) or zoledronic acid (Zol) was administered, received titanium alloy implants in their tibiae and mandibles. An enzyme-linked immunosorbent assay, gene expression analysis and histomorphometry were performed. The results show that ovariectomy, per se, upregulated the expression of genes denoting bone formation in the tibia, bone remodelling in the mandible and apoptosis in the tibia and mandible. Zoledronic acid administration resulted in lower levels of a remodelling marker in serum and downregulated gene expression for inflammation, bone formation, angiogenesis and apoptosis, mainly in the mandible, after 28d of healing. Histomorphometry revealed improved bone-to-implant contact in the tibia, while the opposite was observed in the mandible. The present data show that a systemic single dose of zoledronic acid, in ovariectomised animals, results in site-specific differences in the regulation of genes involved in bone healing and regeneration in association with implant installation. These events occur in parallel with site-specific differences in the rate of osseointegration, indicating diverse tissue responses in the tibia and mandible after zoledronic acid treatment. The zoledronic acid effect on gene expression, during the late phase of healing in the mandible, suggests negative effects by the anti-resorptive agent on osseointegration at that particular site.
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| 8. |
- Elgali, Ibrahim, et al.
(författare)
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Guided bone regeneration using resorbable membrane and different bone substitutes : Early histological and molecular events
- 2016
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 29, s. 409-423
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Tidskriftsartikel (refereegranskat)abstract
- Bone insufficiency remains a major challenge for bone-anchored implants. The combination of guided bone regeneration (GBR) and bone augmentation is an established procedure to restore the bone. However, a proper understanding of the interactions between the bone substitute and GBR membrane materials and the bone-healing environment is lacking. This study aimed to investigate the early events of bone healing and the cellular activities in response to a combination of GBR membrane and different calcium phosphate (CaP) materials. Defects were created in the trabecular region of rat femurs, and filled with deproteinized bovine bone (DBB), hydroxyapatite (HA) or strontium-doped HA (SrHA) or left empty (sham). All the defects were covered with an extracellular matrix membrane. Defects were harvested after 12 h, 3 d and 6 d for histology/histomorphometry, immunohistochemistry and gene expression analyses. Histology revealed new bone, at 6 d, in all the defects. Larger amount of bone was observed in the SrHA-filled defect. This was in parallel with the reduced expression of osteoclastic genes (CR and CatK) and the osteoblast-osteoclast coupling gene (RANKL) in the SrHA defects. Immunohistochemistry indicated fewer osteoclasts in the SrHA defects. The observations of CD68 and periostin-expressing cells in the membrane per se indicated that the membrane may contribute to the healing process in the defect. It is concluded that the bone-promoting effects of Sr in vivo are mediated by a reduction in catabolic and osteoblast-osteoclast coupling processes. The combination of a bioactive membrane and CaP bone substitute material doped with Sr may produce early synergistic effects during GBR. Statement of significance The study provides novel molecular, cellular and structural evidence on the promotion of early bone regeneration in response to synthetic strontium-containing hydroxyapatite (SrHA) substitute, in combination with a resorbable, guided bone regeneration (GBR) membrane. The prevailing view, based mainly upon in vitro data, is that the beneficial effects of Sr are exerted by the stimulation of bone-forming cells (osteoblasts) and the inhibition of bone-resorbing cells (osteoclasts). In contrast, the present study demonstrates that the local effect of Sr in vivo is predominantly via the inhibition of osteoclast number and activity and the reduction of osteoblast-osteoclast coupling. This experimental data will form the basis for clinical studies, using this material as an interesting bone substitute for guided bone regeneration.
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| 9. |
- Jolic, Martina, et al.
(författare)
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Leptin receptor gene deficiency minimally affects osseointegration in rats.
- 2023
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Ingår i: Scientific reports. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic syndrome represents a cluster of conditions such as obesity, hyperglycaemia, dyslipidaemia, and hypertension that can lead to type 2 diabetes mellitus and/or cardiovascular disease. Here, we investigated the influence of obesity and hyperglycaemia on osseointegration using a novel, leptin receptor-deficient animal model, the Lund MetS rat. Machined titanium implants were installed in the tibias of animals with normal leptin receptor (LepR+/+) and those harbouring congenic leptin receptor deficiency (LepR-/-) and were left to heal for 28days. Extensive evaluation of osseointegration was performed using removal torque measurements, X-raymicro-computed tomography, quantitative backscattered electron imaging, Raman spectroscopy, gene expression analysis, qualitative histology, and histomorphometry. Here, we found comparable osseointegration potential at 28days following implant placement in LepR-/- and LepR+/+ rats. However, the low bone volume within the implant threads, higher bone-to-implant contact, and comparable biomechanical stability of the implants point towards changed bone formation and/or remodelling in LepR-/- rats. These findings are corroborated by differences in the carbonate-to-phosphate ratio of native bone measured using Raman spectroscopy. Observations of hypermineralised cartilage islands and increased mineralisation heterogeneity in native bone confirm the delayed skeletal development of LepR-/- rats. Gene expression analyses reveal comparable patterns between LepR-/- and LepR+/+ animals, suggesting that peri-implant bone has reached equilibrium in healing and/or remodelling between the animal groups.
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| 10. |
- Karazisis, Dimitrios, 1977, et al.
(författare)
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The influence of controlled surface nanotopography on the early biological events of osseointegration
- 2017
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 53, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- The early cell and tissue interactions with nanopatterned titanium implants are insufficiently described in vivo. A limitation has been to transfer a pre-determined, well-controlled nanotopography to 3D titanium implants, without affecting other surface parameters, including surface microtopography and chemistry. This in vivo study aimed to investigate the early cellular and molecular events at the bone interface with screw-shaped titanium implants superimposed with controlled nanotopography. Polished and machined titanium implants were firstly patterned with 75-nm semispherical protrusions. Polished and machined implants without nano-patterns were designated as controls. Thereafter, all nanopatterned and control implants were sputter-coated with a 30 nm titanium layer to unify the surface chemistry. The implants were inserted in rat tibiae and samples were harvested after 12 h,1 d and 3 d. In one group, the implants were unscrewed and the implant-adherent cells were analyzed using quantitative polymerase chain reaction. In another group, implants with surrounding bone were harvested en bloc for histology and immunohistochemistry. The results showed that nanotopography downregulated the expression of monocyte chemoattractant protein-1 (MCP-1), at 1 d, and triggered the expression of osteocalcin (DC) at 3 d. This was in parallel with a relatively lower number of recruited CD68-positive macrophages in the tissue surrounding the nanopatterned implants. Moreover, a higher proportion of newly formed osteoid and woven bone was found at the nanopatterned implants at 3 d. It is concluded that nanotopography, per se, attenuates the inflammatory process and enhances the osteogenic response during the early phase of osseointegration. This nanotopography-induced effect appeared to be independent of the underlying microscale topography. This study provides a first line of evidence that pre-determined nanopatterns on clinically relevant, screw-shaped, titanium implants can be recognized by cells in the complex in vivo environment. Until now, most of the knowledge relating to cell interactions with nanopatterned surfaces has been acquired from in vitro studies involving mostly two-dimensional nanopatterned surfaces of varying chemical composition. We have managed to superimpose pre-determined nanoscale topography on polished and micro-rough, screw-shaped, implants, without changes in the microscale topography or chemistry. This was achieved by colloidal lithography in combination with a thin titanium film coating on top of both nanopatterned and control implants. The early events of osseointegration were evaluated at the bone interface to these implants. The results revealed that nanotopography, as such, elicits downregulatory effects on the early recruitment and activity of inflammatory cells while enhancing osteogenic activity and woven bone formation. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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| 11. |
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Palmquist, Anders, 1977, et al.
(författare)
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Bone-titanium oxide interface in humans revealed by transmission electron microscopy and electron tomography
- 2012
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Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 9:67, s. 396-400
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Tidskriftsartikel (refereegranskat)abstract
- Osseointegration, the direct contact between an implant surface and bone tissue, plays a critical role in interfacial stability and implant success. Analysis of interfacial zones at the micro- and nano-levels is essential to determine the extent of osseointegration. In this paper, a series of state-of-the-art microscopy techniques are used on laser-modified implants retrieved from humans. Partially laser-modified implants were retrieved after two and a half months' healing and processed for light and electron microscopy. Light microscopy showed osseointegration, with bone tissue growing both towards and away from the implant surface. Transmission electron microscopy revealed an intimate contact between mineralized bone and the laser-modified surface, including bone growth into the nano-structured oxide. This novel observation was verified by three-dimensional Z-contrast electron tomography, enabling visualization of an apatite layer, with different crystal direction compared with the apatite in the bone tissue, encompassing the nano-structured oxide. In conclusion, the present study demonstrates the nano-scale osseointegration and bonding between apatite and surface-textured titanium oxide. These observations provide novel data in human specimens on the ultrastructure of the titanium–bone interface.
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| 16. |
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| 17. |
- Shah, Furqan A., et al.
(författare)
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Bone without borders - Monetite-based calcium phosphate guides bone formation beyond the skeletal envelope
- 2023
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Ingår i: Bioactive Materials. - : Elsevier BV. - 2452-199X. ; 19, s. 103-114
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Tidskriftsartikel (refereegranskat)abstract
- Calcium phosphates (CaP) represent an important class of osteoconductive and osteoinductive biomaterials. As proof-of-concept, we show how a multi-component CaP formulation (monetite, beta-tricalcium phosphate, and calcium pyrophosphate) guides osteogenesis beyond the physiological envelope. In a sheep model, hollow dome-shaped constructs were placed directly over the occipital bone. At 12 months, large amounts of bone (similar to 75%) occupy the hollow space with strong evidence of ongoing remodelling. Features of both compact bone (osteonal/osteon-like arrangements) and spongy bone (trabeculae separated by marrow cavities) reveal insights into function/need-driven microstructural adaptation. Pores within the CaP also contain both woven bone and vascularised lamellar bone. Osteoclasts actively contribute to CaP degradation/removal. Of the constituent phases, only calcium pyrophosphate persists within osseous (cutting cones) and non-osseous (macrophages) sites. From a translational perspective, this multi-component CaP opens up exciting new avenues for osteotomy-free and minimally-invasive repair of large bone defects and augmentation of the dental alveolar ridge.
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| 18. |
- 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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| 19. |
- Stenlund, Patrik, et al.
(författare)
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Bone response to a novel Ti-Ta-Nb-Zr alloy
- 2015
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 20, s. 165-175
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Tidskriftsartikel (refereegranskat)abstract
- Commercially pure titanium (cp-Ti) is regarded as the state-of-the-art material for bone-anchored dental devices, whereas the mechanically stronger alloy (Ti-6Al-4V), made of titanium, aluminum (Al) and vanadium (V), is regarded as the material of choice for high-load applications. There is a call for the development of new alloys, not only to eliminate the potential toxic effect of Al and V but also to meet the challenges imposed on dental and maxillofacial reconstructive devices, for example. The present work evaluates a novel, dual-stage, acid-etched, Ti-Ta-Nb-Zr alloy implant, consisting of elements that create low toxicity, with the potential to promote osseointegration in vivo. The alloy implants (denoted Ti-Ta-Nb-Zr) were evaluated after 7 days and 28 days in a rat tibia model, with reference to commercially pure titanium grade 4 (denoted Ti). Analyses were performed with respect to removal torque, histomorphometry and gene expression. The Ti-Ta-Nb-Zr showed a significant increase in implant stability over time in contrast to the Ti. Further, the histological and gene expression analyses suggested faster healing around the Ti-Ta-Nb-Zr, as judged by the enhanced remodeling, and mineralization, of the early-formed woven bone and the multiple positive correlations between genes denoting inflammation, bone formation and remodeling. Based on the present experiments, it is concluded that the Ti-Ta-Nb-Zr alloy becomes osseointegrated to at least a similar degree to that of pure titanium implants. This alloy is therefore emerging as a novel implant material for clinical evaluation.
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| 20. |
- 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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| 21. |
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| 22. |
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| 23. |
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| 24. |
- 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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