| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Adewumi, Oluseun, et al.
(författare)
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Characterization of human embryonic stem cell lines by the International Stem Cell Initiative
- 2007
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Ingår i: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 25:7, s. 803-816
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Tidskriftsartikel (refereegranskat)abstract
- The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
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| 3. |
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| 4. |
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| 5. |
- Ahlgren, Eva Christina, et al.
(författare)
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Iron-induced oligomerization of human FXN81-210 and bacterial CyaY frataxin and the effect of iron chelators
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Patients suffering from the progressive neurodegenerative disease Friedreich’s ataxia have reduced expression levels of the protein frataxin. Three major isoforms of human frataxin have been identified, FXN42-210, FXN56-210 and FXN81-210, of which FXN81-210 is considered to be the mature form. Both long forms, FXN42-210 and FXN56-210, have been shown to spontaneously form oligomeric particles stabilized by the extended N-terminal sequence. The short variant FXN81-210, on other hand, has only been observed in the monomeric state. However, a highly homologous E. coli frataxin CyaY, which also lacks an N-terminal extension, has been shown to oligomerize in the presence of iron. To explore the mechanisms of stabilization of short variant frataxin oligomers we compare here the effect of iron on the oligomerization of CyaY and FXN81-210. Using dynamic light scattering, small-angle X-ray scattering, electron microscopy (EM) and cross linking mass spectrometry (MS), we show that at aerobic conditions in the presence of iron both FXN81-210 and CyaY form oligomers. However, while CyaY oligomers are stable over time, FXN81-210 oligomers are unstable and dissociate into monomers after about 24 h. EM and MS studies suggest that within the oligomers FXN81-210 and CyaY monomers are packed in a head-to-tail fashion in ring-shaped structures with potential iron-binding sites located at the interface between monomers. The higher stability of CyaY oligomers can be explained by a higher number of acidic residues at the interface between monomers, which may result in a more stable iron binding. We also show that CyaY oligomers may be dissociated by ferric iron chelators deferiprone and DFO, as well as by the ferrous iron chelator BIPY. Surprisingly, deferiprone and DFO stimulate FXN81-210 oligomerization, while BIPY does not show any effect on oligomerization in this case. The results suggest that FXN81-210 oligomerization is primarily driven by ferric iron, while both ferric and ferrous iron participate in CyaY oligomer stabilization. Analysis of the amino acid sequences of bacterial and eukaryotic frataxins suggests that variations in the position of the acidic residues in helix 1, β-strand 1 and the loop between them may control the mode of frataxin oligomerization.
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| 6. |
- Al-Eryani, Yusra, et al.
(författare)
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Exploring structure and interactions of the bacterial adaptor protein YjbH by crosslinking mass spectrometry
- 2016
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Ingår i: Proteins: Structure, Function and Genetics. - : Wiley. - 0887-3585. ; 84:9, s. 1234-1245
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Tidskriftsartikel (refereegranskat)abstract
- Adaptor proteins assist proteases in degrading specific proteins under appropriate conditions. The adaptor protein YjbH promotes the degradation of an important global transcriptional regulator Spx, which controls the expression of hundreds of genes and operons in response to thiol-specific oxidative stress in Bacillus subtilis. Under normal growth conditions, the transcription factor is bound to the adaptor protein and therefore degraded by the AAA+ protease ClpXP. If this binding is alleviated during stress, the transcription factor accumulates and turns on genes encoding stress-alleviating proteins. The adaptor protein YjbH is thus a key player involved in these interactions but its structure is unknown. To gain insight into its structure and interactions we have used chemical crosslinking mass spectrometry. Distance constraints obtained from the crosslinked monomer were used to select and validate a structure model of YjbH and then to probe its interactions with other proteins. The core structure of YjbH is reminiscent of DsbA family proteins. One lysine residue in YjbH (K177), located in one of the α-helices outside the thioredoxin fold, crosslinked to both Spx K99 and Spx K117, thereby suggesting one side of the YjbH for the interaction with Spx. Another lysine residue that crosslinked to Spx was YjbH K5, located in the long and presumably very flexible N-terminal arm of YjbH. Our crosslinking data lend support to a model proposed based on site-directed mutagenesis where the YjbH interaction with Spx can stabilize and present the C-terminal region of Spx for protease recognition and proteolysis. Proteins 2016; 84:1234–1245.
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| 7. |
- Alm, Rikard, et al.
(författare)
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Detection and identification of protein isoforms using cluster analysis of MALDI-MS mass spectra
- 2006
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 5:4, s. 785-792
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Tidskriftsartikel (refereegranskat)abstract
- We describe an approach to screen large sets of MALDI-MS mass spectra for protein isoforms separated on two-dimensional electrophoresis gels. Mass spectra are matched against each other by utilizing extracted peak mass lists and hierarchical clustering. The output is presented as dendrograms in which protein isoforms cluster together. Clustering could be applied to mass spectra from different sample sets, dates, and instruments, revealed similarities between mass spectra, and was a useful tool to highlight peptide peaks of interest for further investigation. Shared peak masses in a cluster could be identified and were used to create novel peak mass lists suitable for protein identification using peptide mass fingerprinting. Complex mass spectra consisting of more than one protein were deconvoluted using information from other mass spectra in the same cluster. The number of peptide peaks shared between mass spectra in a cluster was typically found to be larger than the number of peaks that matched to calculated peak masses in databases, thus modified peaks are probably among the shared peptides. Clustering increased the number of peaks associated with a given protein.
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| 8. |
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| 9. |
- 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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| 10. |
- Ballo, Ahmed, 1978, et al.
(författare)
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Bone tissue reactions to biomimetic ion-substituted apatite surfaces on titanium implants
- 2012
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Ingår i: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5689 .- 1742-5662. ; 9:72, s. 1615-1624
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the bone tissue response to strontium-and silicon-substituted apatite (Sr-HA and Si-HA) modified titanium (Ti) implants. Sr-HA, Si-HA and HA were grown on thermally oxidized Ti implants by a biomimetic process. Oxidized implants were used as controls. Surface properties, i.e. chemical composition, surface thickness, morphology/pore characteristics, crystal structure and roughness, were characterized with various analytical techniques. The implants were inserted in rat tibiae and block biopsies were prepared for histology, histomorphometry and scanning electron microscopy analysis. Histologically, new bone formed on all implant surfaces. The bone was deposited directly onto the Sr-HA and Si-HA implants without any intervening soft tissue. The statistical analysis showed significant higher amount of bone-implant contact (BIC) for the Si-doped HA modification (P = 0.030), whereas significant higher bone area (BA) for the Sr-doped HA modification (P = 0.034), when compared with the non-doped HA modification. The differences were most pronounced at the early time point. The healing time had a significant impact for both BA and BIC (P < 0.001). The present results show that biomimetically prepared Si-HA and Sr-HA on Ti implants provided bioactivity and promoted early bone formation.
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| 11. |
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| 12. |
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| 13. |
- 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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| 14. |
- 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
-
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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| 15. |
- 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
-
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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| 16. |
- 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
-
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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| 17. |
- Bergman, Annika, et al.
(författare)
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Germline mutation screening of the Saethre-Chotzen-associated genes TWIST1 and FGFR3 in families with BRCA1/2-negative breast cancer
- 2009
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Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Taylor & Francis. - 0284-4311 .- 1651-2073. ; 43:5, s. 251-255
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Tidskriftsartikel (refereegranskat)abstract
- Saethre-Chotzen syndrome is one of the most common craniosynostosis syndromes. It is an autosomal dominantly inherited disorder with variable expression that is caused by germline mutations in the TWIST1 gene or more rarely in the FGFR2 or FGFR3 genes. We have previously reported that patients with Saethre-Chotzen syndrome have an increased risk of developing breast cancer. Here we have analysed a cohort of 26 women with BRCA1/2-negative hereditary breast cancer to study whether a proportion of these families might have mutations in Saethre-Chotzen-associated genes. DNA sequence analysis of TWIST1 showed no pathogenic mutations in the coding sequence in any of the 26 patients. MLPA (multiplex ligation-dependent probe amplification)-analysis also showed no alterations in copy numbers in any of the craniofacial disorder genes MSX2, ALX4, RUNX2, EFNB1, TWIST1, FGFR1, FGFR2,FGFR3, or FGFR4. Taken together, our findings indicate that mutations in Saethre-Chotzen-associated genes are uncommon or absent in BRCA1/2-negative patients with hereditary breast cancer.
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| 18. |
- Brinkfeldt, Klas, et al.
(författare)
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Microshutters for MEMS-based time-of-flight measurements in space
- 2011
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Ingår i: Proceedings of the IEEE International Conference on Micro Electro Mechanical Systems (MEMS). - 1084-6999. - 9781424496327 ; , s. 597-600
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Konferensbidrag (refereegranskat)abstract
- This paper reports on the fabrication, integration and first operation of a mechanical microshutter in a time-of-flight (TOF) based ion detector in space. The microshutter is fabricated from a silicon on insulator (SOI) wafer and operated in a resonance mode, 306 kHz. Open time of the shutter is 100 ns. The microshutters are integrated in the PRIMA instrument, which is part of the payload on the Swedish PRISMA mission. PRISMA was successfully launched into low Earth orbit on June 15, 2010.
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| 19. |
- Brinkfelt, Klas, 1976, et al.
(författare)
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Microshutters for space physics time of flight applications
- 2010
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Ingår i: 21st Micromechanics and Micro systems Europe workshop, 26-29 September 2010, Enschede, The Netherlands. ; , s. 140-143
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Konferensbidrag (refereegranskat)abstract
- In present time-of-flight (TOF) mass and energy spectrometers in experimental space plasmaphysics applications, the resolution is limited by the fact that the particle to be measured loses part of its energyin the generation of the start pulse. To improve the resolution, a fast micromechanical shutter system togenerate the start signal has been developed. The microshutter is included in the PRIMA (PRIsma MassAnalyzer) ion detector on-board the Swedish PRISMA mission, which will be launched into low Earth orbit onJune 15, 2010.
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| 20. |
- Brånemark, Rickard, 1960, et al.
(författare)
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Bone response to laser-induced micro- and nano-size titanium surface features.
- 2011
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Ingår i: Nanomedicine : nanotechnology, biology, and medicine. - : Elsevier BV. - 1549-9642 .- 1549-9634.
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Tidskriftsartikel (refereegranskat)abstract
- The present study explored whether laser-induced, site-specific implant surface modifications with micro- and nano-scale topography were able to promote bone formation. The aim was to evaluate the biomechanical and histological response to partly laser-modified titanium implants compared with machined implants. After an early 8-week healing period in rabbit tibia and femur, a 250% increase in removal torque was demonstrated for the partly laser-modified surface. Further, different fracture mechanisms were demonstrated for the two surfaces. Histologically, significantly more bone was found in direct contact with the laser-modified surface for the implants in the tibia sites, while a similar amount of bone tissue was observed in contact with the implant in the femoral sites. In conclusion, an improved bone-implant interface anchorage was promoted by an increase in micro- and nano-scale implant surface topography and surface oxide induced by topological laser treatment.
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| 21. |
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| 22. |
- 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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| 23. |
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| 24. |
- Carlstedt, Anders, et al.
(författare)
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Management of Diastasis of the Rectus Abdominis Muscles : Recommendations for Swedish National Guidelines
- 2021
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Ingår i: Scandinavian Journal of Surgery. - : Sage Publications. - 1457-4969 .- 1799-7267. ; 10:3, s. 452-459
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diastasis of the rectus abdominis muscle is a common condition. There are no generally accepted criteria for diagnosis or treatment of diastasis of the rectus abdominis muscle, which causes uncertainty for the patient and healthcare providers alike. Methods: The consensus document was created by a group of Swedish surgeons and based on a structured literature review and practical experience. Results: The proposed criteria for diagnosis and treatment of diastasis of the rectus abdominis muscle are as follows: (1) Diastasis diagnosed at clinical examination using a caliper or ruler for measurement. Diagnostic imaging by ultrasound or other imaging modality, should be performed when concurrent umbilical or epigastric hernia or other cause of the patient's symptoms cannot be excluded. (2) Physiotherapy is the firsthand treatment for diastasis of the rectus abdominis muscle. Surgery should only be considered in diastasis of the rectus abdominis muscle patients with functional impairment, and not until the patient has undergone a standardized 6-month abdominal core training program. (3) The largest width of the diastasis should be at least 5 cm before surgical treatment is considered. In case of pronounced abdominal bulging or concomitant ventral hernia, surgery may be considered in patients with a smaller diastasis. (4) When surgery is undertaken, at least 2 years should have elapsed since last childbirth and future pregnancy should not be planned. (5) Plication of the linea alba is the firsthand surgical technique. Other techniques may be used but have not been found superior. Discussion: The level of evidence behind these statements varies, but they are intended to lay down a standard strategy for treatment of diastasis of the rectus abdominis muscle and to enable uniformity of management.
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| 25. |
- Emanuelsson, Peter
(författare)
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Alternatives in the treatment of abdominal rectus muscle diastasis : an evaluation
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Abdominal rectus diastasis (ARD) is defined as a widening of the distance between the two rectus muscles located on either side of the Linea Alba (LA). A width of more than 3 cm is, in this thesis, considered as pathological. There are several reasons why ARD occurs, where pregnancy is one of the most common. Genetic variations in collagen composition, massive weight loss, and previous abdominal surgery are others. Patients with ARD usually perceive no pain at rest whereas discomfort, pain, corset instability and bulging of the abdominal wall are symptoms appearing during physical activity. Conclusive data regarding the most appropriate treatment of ARD are sparse, and studies with focus on abdominal wall function and quality of life after repair are lacking. Furthermore, no reliable data exist regarding evaluation of patients with ARD prior to surgery and the relevance of specific symptoms, width of ARD and abdominal wall strength. The overall aim of the present thesis was to evaluate the outcome of two surgical methods with regard to relapse of ARD; repair with a retromuscular mesh or double row self-retaining suture. Quality-of-life, pain and abdominal muscle strength were important secondary endpoints in the outcome of repair. Secondary aims were to evaluate: the effects of a dedicated training programme on symptoms and complaints from ARD; imaging and measurements of the ARD width prior to surgery; and to develop a reliable method for evaluation of abdominal wall strength. Material and methods: Study I. The validity and reliability of the Biodex System-4, was tested in ten healthy volunteers and ten patients with ARD ≥3 cm. The reliability of isokinetic and isometric muscle strength was assessed by test-retest with one week in between. Validity was tested by IPAQ (International Physical Activity Questionnaire) and VAS-assessment of patient-perceived muscle strength. Study II. The width of ARD was evaluated clinically, with CT-scan and intra-operatively in 55 patients. Agreement between these modalities was evaluated to determine the most relevant measurement. Study III. Early complications during the initial three postoperative months were monitored in 56 patients of whom 29 were randomised to repair with a retromuscular mesh and 27 to the Quill™ suture technique. All patients presented with an ARD wider than 3 cm. Study IV. The same 56 patients randomised to surgery as in Study III were compared to 30 patients assigned to a training programme. Follow-up for the operated patients was at 1 year while training outcome was studied after the stated period of 3 months. Results: The reliability of the Biodex System-4 was excellent as shown by ICC (Intra Class Correlation) statistics. The internal validity was excellent when compared to VAS using Spearman’s test. The external validity showed no correlation between IPAQ and isometric muscle strength using the Kendall-Tau test (Study I). Evaluation of the three methods to assess ARD showed a strong agreement (high CCC; Concordance Correlation Coefficient) between the clinical and intraoperative measurements whereas CT-scan and intraoperative measurements did not show agreement (low CCC). CT measurements underestimated the width of the ARD (Study II). Minor complications were observed three months after surgery. No significant difference between the two surgical groups in terms of early complication and perceived pain was observed. Patients in the mesh group experienced greater improvement in abdominal muscle strength (Study III). One year after surgery one recurrence was documented in the Quill group and five encapsulated seromas were distributed with no difference between the two surgical groups. Biodex System-4 showed significant improvement in all muscle strength modalities with the three methods. Quality-of-life (SF-36) domains were all significantly improved one year after surgery (p<0.001) with the exception of bodily pain (BP) in the physiotherapy group after three months of training (Study IV). Conclusions: The prospective randomised trial has shown that patients with an ARD wider than 3 cm have physical symptoms and poorer quality of life than an age-matched Swedish population. Surgical intervention improves patient comfort and improves quality of life. There is no difference between the Quill technique and retromuscular mesh in the effect on abdominal wall stability, with a similar complication rate one year after surgery. Dedicated training strengthens abdominal muscles objectively but does not improve perceived muscle strength or pain in the abdominal wall.
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| 26. |
- Emanuelsson, Peter, et al.
(författare)
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Analysis of the abdominal musculo-aponeurotic anatomy in rectus diastasis : comparison of CT scanning and preoperative clinical assessment with direct measurement intraoperatively
- 2014
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Ingår i: Hernia. - Paris : Springer. - 1265-4906 .- 1248-9204. ; 18:4, s. 465-471
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate and compare the consistency of agreement of two methods for measuring abdominal rectus diastasis (ARD), preoperative computed tomography (CT) scanning and preoperative clinical assessment were compared with direct measurement intraoperatively.METHODS: Fifty-five consecutive patients were retrieved from an ongoing prospective randomised trial comparing two operative techniques for the repair of ARD. All patients underwent a preoperative clinical assessment and CT scan, and the results were compared with intraoperative measurement of the ARD width. Agreement between methods was described with Bland-Altman plots (BA plots) and calculated using Lin's Concordance Correlation Coefficient (CCC).RESULTS: The median width of the diastasis was 4.0 cm in the upper midline and 3.0 cm in the lower midline for the intraoperative measurement. BA plots showed that measurements on CT and intraoperatively are not in agreement in the lower midline, whereas the agreement was stronger between the clinical and the intraoperative method. The CCC was higher for clinical vs. intraoperative measurement (0.479) than for CT vs. intraoperative measurement (-0.002) in the lower midline, although the agreement was over all low. CT scanning underestimated the width of the ARD when compared to 87 % of preoperative clinical assessments, and 83 % of intraoperative measurements. Preoperative clinical assessment overestimated ARD in 35 % when compared with intraoperative measurements.CONCLUSION: Clinical assessment prior to surgery provides more accurate information than CT scanning in the assessment of ARD width. CT scanning underestimates ARD width when compared with intraoperative measurement.
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| 27. |
- Emanuelsson, Peter, et al.
(författare)
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Early complications, pain, and quality of life after reconstructive surgery for abdominal rectus muscle diastasis : a 3-month follow-up
- 2014
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Ingår i: Journal of Plastic, Reconstructive & Aesthetic Surgery. - : Elsevier. - 1748-6815 .- 1878-0539. ; 67:8, s. 1082-1088
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of this study was to evaluate early complications following retromuscular mesh repair with those after dual layer suture of the anterior rectus sheath in a randomised controlled clinical trial for abdominal rectus muscle diastasis (ARD).METHODS: Patients with an ARD wider than 3 cm and clinical symptoms related to the ARD were included in a prospective randomised study. They were assigned to either retromuscular inset of a lightweight polypropylene mesh or to dual closure of the anterior rectus fascia using Quill self-locking technology. All patients completed a validated questionnaire for pain assessment (Ventral Hernia Pain Questionnaire, VHPQ) and for quality of life (SF36) prior to and 3 months after surgery.RESULTS: The most frequently seen adverse event was minor wound infection. Of the patients, 14/57 had a superficial wound infection; five related to Quill and nine to mesh repair. No deep wound infections were reported. Patient rating for subjective muscular improvement postoperatively was better in the mesh technique group with a mean of 6.9 (range 0-10) compared to a mean of 4.8 (range 0-10) in the Quill group (p=0.01). The pre- and post-operative SF36 scores improved in both groups.CONCLUSIONS: There was no significant difference between the two surgical techniques in terms of early complications and perceived pain at the 3-month follow-up. Both techniques may be considered equally reliable for ARD repair in terms of adverse outcomes during the early postoperative phase, even though patients operated with a mesh experienced better improvement in muscular strength.
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| 28. |
- Emanuelsson, Peter, et al.
(författare)
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Operative correction of abdominal rectus diastasis (ARD) reduces pain and improves abdominal wall muscle strength : a randomized, prospective trial comparing retromuscular mesh repair to double-row, self-retaining sutures
- 2016
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Ingår i: Surgery. - : Elsevier. - 0039-6060 .- 1532-7361. ; 160:5, s. 1367-1375
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The primary aim of this prospective, randomized, clinical, 2-armed trial was to evaluate the risk for recurrence using 2 different operative techniques for repair of abdominal rectus diastasis. Secondary aims were comparison of pain, abdominal muscle strength, and quality of life and to compare those outcomes to a control group receiving physical training only.METHODS: Eighty-six patients were enrolled. Twenty-nine patients were allocated to retromuscular polypropylene mesh and 27 to double-row plication with Quill technology. Thirty-two patients participated in a 3-month training program. Diastasis was evaluated with computed tomography scan and clinically. Pain was assessed using the ventral hernia pain questionnaire, a quality-of-life survey, SF-36, and abdominal muscle strength using the Biodex System-4.RESULTS: One early recurrence occurred in the Quill group, 2 encapsulated seromas in the mesh group, and 3 in the suture group. Significant improvements in perceived pain, the ventral hernia pain questionnaire, and quality of life appeared at the 1-year follow-up with no difference between the 2 operative groups. Significant muscular improvement was obtained in all groups (Biodex System-4). Patient perceived gain in muscle strength assessed with a visual analog scale improved similarly in both operative groups. This improvement was significantly greater than that seen in the training group. Patients in the training group still experienced bodily pain at follow-up.CONCLUSION: There was no difference between the Quill technique and retromuscular mesh in the effect on abdominal wall stability, with a similar complication rate 1 year after operation. An operation improves functional ability and quality of life. Training strengthens the abdominal muscles, but patients still experience discomfort and pain.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
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| 33. |
- Farjana, Sadia, 1983, et al.
(författare)
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Realizing a 140 GHz Gap Waveguide–Based Array Antenna by Low-Cost Injection Molding and Micromachining
- 2021
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Ingår i: Journal of Infrared, Millimeter and Terahertz Waves. - : Springer. - 1866-6892 .- 1866-6906. ; 42:8, s. 893-914
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a novel micromachining process to fabricate a 140 GHz planar antenna based on gap waveguide technology to be used in the next-generation backhauling links. The 140 GHz planar array antenna consists of three layers, all of which have been fabricated using polymer-based microfabrication and injection molding. The 140 GHz antenna has the potential to be used as an element in a bigger 3D array in a line-of-sight (LOS) multiple input multiple output (MIMO) configuration to boost the network capacity. In this work, we focus on the fabrication of a single antenna array element based on gap waveguide technology. Depending on the complexity of each antenna layer’s design, three different micromachining techniques, SU8 fabrication, polydimethylsiloxane (PDMS) molding, and injection molding of the polymer (OSTEMER), together with gold (Au) coating, have been utilized to fabricate a single 140 GHz planar array antenna. The input reflection coefficient was measured to be below − 11 dB over a 14% bandwidth from 132 to 152 GHz, and the antenna gain was measured to be 31 dBi at 140 GHz, both of which are in good agreement with the simulations. © 2021, The Author(s).
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| 34. |
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| 35. |
- Grandfield, Kathryn, et al.
(författare)
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Bone response to free form fabricated hydroxyapatite and zirconia scaffolds : a transmission electron microscopy study in the human maxilla
- 2012
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Ingår i: Clinical Implant Dentistry and Related Research. - : Wiley. - 1523-0899 .- 1708-8208. ; 14:3, s. 461-469
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Tidskriftsartikel (refereegranskat)abstract
- Background: Understanding the interfacial reactions to synthetic bone regenerative scaffolds in vivo is fundamental for improving osseointegration and osteogenesis. Using transmission electron microscopy, it is possible to study the biological response of hydroxyapatite (HA) and zirconia (ZrO2) scaffolds at the nanometer scale.Purpose: In this study, the bone-bonding abilities of HA and ZrO2 scaffolds produced by free-form fabrication were evaluated in the human maxilla at 3 months and 7 months.Materials and Methods: HA and ZrO2 scaffolds (ø: 3 mm) were implanted in the human maxilla, removed with surrounding bone, embedded in resin, and sectioned. A novel focused ion beam (FIB) sample preparation technique enabled the production of thin lamellae for study by scanning transmission electron microscopy.Results: Interface regions were investigated using high-angle annular dark-field imaging and energy-dispersive X-ray spectroscopy analysis. Interfacial apatite layers of 80 nm and 50 nm thickness were noted in the 3- and 7-month HA samples, respectively, and bone growth was discovered in micropores up to 10 µm into the samples.Conclusions: The absence of an interfacial layer in the ZrO2 samples suggest the formation of a direct contact with bone, while HA, which bonds through an apatite layer, shows indications of resorption with increasing implantation time. This study demonstrates the potential of HA and ZrO2 scaffolds for use as bone regenerative materials.
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| 36. |
- Grandfield, Kathryn, et al.
(författare)
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Free form fabricated features on CoCr implants with and without hydroxyapatite coating in vivo : a comparative study of bone contact and bone growth induction
- 2011
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Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 22:4, s. 899-906
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Tidskriftsartikel (refereegranskat)abstract
- The current study evaluates the in vivo response to free form fabricated cobalt chromium (CoCr) implants with and without hydroxyapatite (HA) plasma sprayed coatings. The free form fabrication method allowed for integration of complicated pyramidal surface structures on the cylindrical implant. Implants were press fit into the tibial metaphysis of nine New Zealand white rabbits. Animals were sacrificed and implants were removed and embedded. Histological analysis, histomorphometry and electron microscopy studies were performed. Focused ion beam was used to prepare thin sections for high-resolution transmission electron microscopy examination. The fabricated features allowed for effective bone in-growth and firm fixation after 6 weeks. Transmission electron microscopy investigations revealed intimate bone-implant integration at the nanometre scale for the HA coated samples. In addition, histomorphometry revealed a significantly higher bone contact on HA coated implants compared to native CoCr implants. It is concluded that free form fabrication in combination with HA coating improves the early fixation in bone under experimental conditions.
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| 37. |
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| 38. |
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| 39. |
- Heins, Nico, et al.
(författare)
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Clonal derivation and characterization of human embryonic stem cell lines.
- 2006
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Ingår i: Journal of biotechnology. - : Elsevier BV. - 0168-1656 .- 1873-4863. ; 122:4, s. 511-20
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Tidskriftsartikel (refereegranskat)abstract
- Human embryonic stem cells (hESC) are isolated as clusters of cells from the inner cell mass of blastocysts and thus should formally be considered as heterogeneous cell populations. Homogenous hESC cultures can be obtained through subcloning. Here, we report the clonal derivation and characterization of two new hESC lines from the parental cell line SA002 and the previously clonally derived cell line AS034.1, respectively. The hESC line SA002 was recently reported to have an abnormal karyotype (trisomy 13), but within this population of cells we observed rare individual cells with an apparent normal karyotype. At a cloning efficiency of 5%, we established 33 subclones from SA002, out of which one had a diploid karyotype and this subline was designated SA002.5. From AS034.1 we established one reclone designated AS034.1.1 at a cloning efficiency of 0.1%. These two novel sublines express cell surface markers indicative of undifferentiated hESC (SSEA-3, SSEA-4, TRA-1-60, and TRA-1-81), Oct-4, alkaline phosphatase, and they display high telomerase activity. In addition, the cells are pluripotent and form derivatives of all three embryonic germ layers in vitro as well as in vivo. These results, together with the clonal character of SA002.5 and AS034.1.1 make these homogenous cell populations very useful for hESC based applications in drug development and toxicity testing. In addition, the combination of the parental trisomic hESC line SA002 and the diploid subclone SA002.5 provides a unique experimental system to study the molecular mechanisms underlying the pathologies associated with trisomy 13.
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| 40. |
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| 41. |
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Johansson, Peter, et al.
(författare)
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SPECLUST: a web tool for clustering of mass spectra
- 2007
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- SPECLUST is a web tool for hierarchical clustering of peptide mass spectra obtained from protease-digested proteins. Mass spectra are clustered according to the peptide masses they contain, such that mass spectra containing similar masses are clustered together. Hierarchical clustering of mass spectra with SPECLUST can in particular be useful for MS-screening of large proteomic data sets derived from 2D-gels. SPECLUST can also be used to identify masses shared by mass spectra. Masses present in the majority of the mass spectra in a data set are likely to be contaminants. With SPECLUST, MS/MS can be focused on non-contaminant shared masses in a cluster, facilitating investigations of protein isoforms. Within a cluster, shared and unique masses represent peptides from regions that are similar and different, respectively, between protein isoforms. Taken together, SPECLUST is a versatile tool for analysis of mass spectrometry data. Availability: SPECLUST is freely available at http://bioinfo.thep.lu.se/speclust.html.
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| 46. |
- 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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| 47. |
- Karazisis, Dimitrios, 1977, et al.
(författare)
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The effects of controlled nanotopography, machined topography and their combination on molecular activities, bone formation and biomechanical stability during osseointegration
- 2021
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 136, s. 279-290
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Tidskriftsartikel (refereegranskat)abstract
- The initial cellular and molecular activities at the bone interface of implants with controlled nanoscale topography and microscale roughness have previously been reported. However, the effects of such surface modifications on the development of osseointegration have not yet been determined. This study investigated the molecular events and the histological and biomechanical development of the bone interface in implants with nanoscale topography, microscale roughness or a combination of both. Polished and machined titanium implants with and without controlled nanopatterning (75 nm protrusions) were produced using colloidal lithography and coated with a thin titanium layer to unify the chemistry. The implants were inserted in rat tibiae and subjected to removal torque (RTQ) measurements, molecular analyses and histological analyses after 6, 21 and 28 days. The results showed that nanotopography superimposed on microrough, machined, surfaces promoted an early increase in RTQ and hence produced greater implant stability at 6 and 21 days. Two-way MANOVA revealed that the increased RTQ was influenced by microscale roughness and the combination of nanoscale and microscale topographies. Furthermore, increased bone-implant contact (BIC) was observed with the combined nanopatterned machined surface, although MANOVA results implied that the increased BIC was mainly dependent on microscale roughness. At the molecular level, the nanotopography, per se, and in synergy with microscale roughness, downregulated the expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). In conclusion, controlled nanotopography superimposed on microrough machined implants promoted implant stability during osseointegration. Nanoscale-driven mechanisms may involve attenuation of the inflammatory response at the titanium implant site. Statement of Significance: The role of combined implant microscale and nanotopography features for osseointegration is incompletely understood. Using colloidal lithography technique, we created an ordered nanotopography pattern superimposed on screwshaped implants with microscale topography. The midterm and late molecular, bone-implant contact and removal torque responses were analysed in vivo. Nanotopography superimposed on microrough, machined, surfaces promoted the implant stability, influenced by microscale topography and the combination of nanoscale and microscale topographies. Increased bone-implant contact was mainly dependent on microscale roughness whereas the nanotopography, per se, and in synergy with microscale roughness, attenuated the proinflammatory tumor necrosis factor alpha (TNF-α) expression. It is concluded that microscale and nanopatterns provide individual as well as synergistic effects on molecular, morphological and biomechanical implant-tissue processes in vivo.
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| 48. |
- 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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| 49. |
- Karazisis, Dimitrios, et al.
(författare)
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The role of well-defined nanotopography of titanium implants on osseointegration : Cellular and molecular events in vivo
- 2016
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Ingår i: International Journal of Nanomedicine. - : Dove Medical Press Ltd.. - 1176-9114 .- 1178-2013. ; 11, s. 1367-1382
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Mechanisms governing the cellular interactions with well-defined nanotopography are not well described in vivo. This is partly due to the difficulty in isolating a particular effect of nanotopography from other surface properties. This study employed colloidal lithography for nanofabrication on titanium implants in combination with an in vivo sampling procedure and different analytical techniques. The aim was to elucidate the effect of well-defined nanotopography on the molecular, cellular, and structural events of osseointegration. Materials and methods: Titanium implants were nanopatterned (Nano) with semispherical protrusions using colloidal lithography. Implants, with and without nanotopography, were implanted in rat tibia and retrieved after 3, 6, and 28 days. Retrieved implants were evaluated using quantitative polymerase chain reaction, histology, immunohistochemistry, and energy dispersive X-ray spectroscopy (EDS). Results: Surface characterization showed that the nanotopography was well defined in terms of shape (semispherical), size (79±6 nm), and distribution (31±2 particles/μm2). EDS showed similar levels of titanium, oxygen, and carbon for test and control implants, confirming similar chemistry. The molecular analysis of the retrieved implants revealed that the expression levels of the inflammatory cytokine, TNF-α, and the osteoclastic marker, CatK, were reduced in cells adherent to the Nano implants. This was consistent with the observation of less CD163-positive macrophages in the tissue surrounding the Nano implant. Furthermore, periostin immunostaining was frequently detected around the Nano implant, indicating higher osteogenic activity. This was supported by the EDS analysis of the retrieved implants showing higher content of calcium and phosphate on the Nano implants. Conclusion: The results show that Nano implants elicit less periimplant macrophage infiltration and downregulate the early expression of inflammatory (TNF-α) and osteoclastic (CatK) genes. Immunostaining and elemental analyses show higher osteogenic activity at the Nano implant. It is concluded that an implant with the present range of well-defined nanocues attenuates the inflammatory response while enhancing mineralization during osseointegration.
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| 50. |
- Karazisis, Dimitrios, 1977, et al.
(författare)
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The role of well-defined nanotopography of titanium implants on osseointegration: cellular and molecular events in vivo
- 2016
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Ingår i: International Journal of Nanomedicine. - : Informa UK Limited. - 1178-2013 .- 1176-9114. ; 11, s. 1367-1381
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Mechanisms governing the cellular interactions with well-defined nanotopography are not well described in vivo. This is partly due to the difficulty in isolating a particular effect of nanotopography from other surface properties. This study employed colloidal lithography for nanofabrication on titanium implants in combination with an in vivo sampling procedure and different analytical techniques. The aim was to elucidate the effect of well-defined nanotopography on the molecular, cellular, and structural events of osseointegration. Materials and methods: Titanium implants were nanopatterned (Nano) with semispherical protrusions using colloidal lithography. Implants, with and without nanotopography, were implanted in rat tibia and retrieved after 3, 6, and 28 days. Retrieved implants were evaluated using quantitative polymerase chain reaction, histology, immunohistochemistry, and energy dispersive X-ray spectroscopy (EDS). Results: Surface characterization showed that the nanotopography was well defined in terms of shape (semispherical), size (79 +/- 6 nm), and distribution (31 +/- 2 particles/mu m(2)). EDS showed similar levels of titanium, oxygen, and carbon for test and control implants, confirming similar chemistry. The molecular analysis of the retrieved implants revealed that the expression levels of the inflammatory cytokine, TNF-alpha, and the osteoclastic marker, CatK, were reduced in cells adherent to the Nano implants. This was consistent with the observation of less CD163-positive macrophages in the tissue surrounding the Nano implant. Furthermore, periostin immunostaining was frequently detected around the Nano implant, indicating higher osteogenic activity. This was supported by the EDS analysis of the retrieved implants showing higher content of calcium and phosphate on the Nano implants. Conclusion: The results show that Nano implants elicit less periimplant macrophage infiltration and downregulate the early expression of inflammatory (TNF-alpha) and osteoclastic (CatK) genes. Immunostaining and elemental analyses show higher osteogenic activity at the Nano implant. It is concluded that an implant with the present range of well-defined nanocues attenuates the inflammatory response while enhancing mineralization during osseointegration.
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