| 1. |
- Martinez-Sanz, Elena, et al.
(författare)
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Minimally invasive mandibular bone augmentation using injectable hydrogels
- 2012
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Ingår i: Journal of Tissue Engineering and Regenerative Medicine. - : Hindawi Limited. - 1932-6254. ; 6:S3, s. s15-s23
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Tidskriftsartikel (refereegranskat)abstract
- Hyaluronic acid-based hydrogels are proven biocompatible materials and excellent carriers of bone morphogenetic protein-2 (BMP-2) that have been successfully tested for bone generation in vivo. Different formulations, with or without nanohydroxyapatite, have shown promise for craniofacial applications. In this study, 28 rats were used to investigate whether it is possible to achieve mandibular bone augmentation upon injection of novel hyaluronic acid-based hydrogels containing nanohydroxyapatite and different concentrations of BMP-2 (0, 5 and 150ÎŒg/ml). The biomaterials were injected subperiosteally through fine needles into the innate mandibular diastema, imitating a clinical procedure for resorbed mandibles. No incisions, flaps or sutures were necessary. After 8weeks the mandibles were evaluated by peripheral quantitative computed tomography (pQCT), micro-computed tomography (ÎŒCT), histology, immunohistochemistry and fluorochrome labelling. As a result, engineered bone was observed in all treated mandibles, with a statistically significant increase in mandibular bone volume correlated with the amount of BMP-2 loaded in the hydrogel formula. We therefore demonstrated that minimally invasive mandibular bone augmentation is possible upon injection in rats, when using the appropriate injectable scaffolds. This represents an attractive clinical alternative for oral implantology patients.
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| 2. |
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| 3. |
- Pujari-Palmer, Michael, et al.
(författare)
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Pyrophosphate Stimulates Differentiation, Matrix Gene Expression and Alkaline Phosphatase Activity in Osteoblasts
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:10
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Tidskriftsartikel (refereegranskat)abstract
- Pyrophosphate is a potent mitogen, capable of stimulating proliferation in multiple cell types, and a critical participant in bone mineralization. Pyrophosphate can also affect the resorption rate and bioactivity of orthopedic ceramics. The present study investigated whether calcium pyrophosphate affected proliferation, differentiation and gene expression in early (MC3T3 pre-osteoblast) and late stage (SAOS-2 osteosarcoma) osteoblasts. Pyrophosphate stimulated peak alkaline phosphatase activity by 50% and 150% at 100 mu M and 0.1 mu M in MC3T3, and by 40% in SAOS-2. The expression of differentiation markers collagen 1 (COL1), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) were increased by an average of 1.5, 2, 2 and 3 fold, by high concentrations of sodium pyrophosphate (100 mu M) after 7 days of exposure in MC3T3. COX-2 and ANK expression did not differ significantly from controls in either treatment group. Though both high and low concentrations of pyrophosphate stimulate ALP activity, only high concentrations (100 mu M) stimulated osteogenic gene expression. Pyrophosphate did not affect proliferation in either cell type. The results of this study confirm that chronic exposure to pyrophosphate exerts a physiological effect upon osteoblast differentiation and ALP activity, specifically by stimulating osteoblast differentiation markers and extracellular matrix gene expression.
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| 4. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 5. |
- Abrahamsson, Thomas, et al.
(författare)
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Low diversity of the gut microbiota in infants with atopic eczema
- 2012
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Ingår i: Journal of Allergy and Clinical Immunology. - New York, USA : Elsevier BV. - 0091-6749 .- 1097-6825. ; 129:2, s. 434-U244
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing incidence of allergic disease. The advent of powerful, cultivation-free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts. OBJECTIVE: We sought to assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development. METHODS: Microbial diversity and composition were analyzed with barcoded 16S rDNA 454-pyrosequencing in stool samples at 1 week, 1 month, and 12 months of age in 20 infants with IgE-associated eczema and 20 infants without any allergic manifestation until 2 years of age (ClinicalTrials.gov ID NCT01285830). RESULTS: Infants with IgE-associated eczema had a lower diversity of the total microbiota at 1 month (P= .004) and a lower diversity of the bacterial phylum Bacteroidetes and the genus Bacteroides at 1 month (P= .02 and P= .01) and the phylum Proteobacteria at 12 months of age (P= .02). The microbiota was less uniform at 1 month than at 12 months of age, with a high interindividual variability. At 12 months, when the microbiota had stabilized, Proteobacteria, comprising gram-negative organisms, were more abundant in infants without allergic manifestation (Empirical Analysis of Digital Gene Expression in R edgeR test: P= .008, q= 0.02). CONCLUSION: Low intestinal microbial diversity during the first month of life was associated with subsequent atopic eczema.
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| 6. |
- Abrahamsson, Thomas, et al.
(författare)
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Low gut microbiota diversity in early infancy precedes asthma at school age
- 2014
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 44:6, s. 842-850
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Tidskriftsartikel (refereegranskat)abstract
- Background Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age. Objective To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema. Methods The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1week, 1month and 12months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7years of age (ClinicalTrials.gov ID NCT01285830). Results Children developing asthma (n=8) had a lower diversity of the total microbiota than non-asthmatic children at 1week (P=0.04) and 1month (P=0.003) of age, whereas allergic rhinoconjunctivitis (n=13), eczema (n=12) and positive skin prick reactivity (n=14) at 7years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease. Conclusion and Clinical Relevance Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.
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| 7. |
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| 8. |
- Arnander, Claes, et al.
(författare)
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Three-Dimensional Technology and Bone Morphogenetic Protein in Frontal Bone Reconstruction
- 2006
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Ingår i: Journal of Craniofacial Surgery. ; 17:2, s. 275-279
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Tidskriftsartikel (refereegranskat)abstract
- Osteoinductive bone morphogenetic proteins (BMPs) may be used in humans to facilitate healing of bony defects. The effect of different BMPs is, as with many other growth factors, highly dependent on the delivery vehicle. Bovine type I collagen is currently used in the clinical setting as a carrier and has been approved in several countries for human use. Here, we report the reconstruction of a frontal bone defect using heparin together with bovine type I collagen, hyaluronic acid, and fibrin as vehicles for BMP-2. A bony structure was created on the back of the patient by treating the latissimus dorsi muscle with the growth factor. A polyamide mold was used as a template to achieve the desired shape. The bone structure was transplanted into the defect site via microsurgical techniques. Although the prefabricated bone was not large enough tocover the entire frontal defect, the reconstruction was completed by using an additional cranial implant.
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| 9. |
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| 10. |
- Aspholm, Marina, et al.
(författare)
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SabA is the H. pylori hemagglutinin and is polymorphic in binding to sialylated glycans.
- 2006
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Ingår i: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374 .- 1553-7366. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- Adherence of Helicobacter pylori to inflamed gastric mucosa is dependent on the sialic acid-binding adhesin (SabA) and cognate sialylated/fucosylated glycans on the host cell surface. By in situ hybridization, H. pylori bacteria were observed in close association with erythrocytes in capillaries and post-capillary venules of the lamina propria of gastric mucosa in both infected humans and Rhesus monkeys. In vivo adherence of H. pylori to erythrocytes may require molecular mechanisms similar to the sialic acid-dependent in vitro agglutination of erythrocytes (i.e., sialic acid-dependent hemagglutination). In this context, the SabA adhesin was identified as the sialic acid-dependent hemagglutinin based on sialidase-sensitive hemagglutination, binding assays with sialylated glycoconjugates, and analysis of a series of isogenic sabA deletion mutants. The topographic presentation of binding sites for SabA on the erythrocyte membrane was mapped to gangliosides with extended core chains. However, receptor mapping revealed that the NeuAcalpha2-3Gal-disaccharide constitutes the minimal sialylated binding epitope required for SabA binding. Furthermore, clinical isolates demonstrated polymorphism in sialyl binding and complementation analysis of sabA mutants demonstrated that polymorphism in sialyl binding is an inherent property of the SabA protein itself. Gastric inflammation is associated with periodic changes in the composition of mucosal sialylation patterns. We suggest that dynamic adaptation in sialyl-binding properties during persistent infection specializes H. pylori both for individual variation in mucosal glycosylation and tropism for local areas of inflamed and/or dysplastic tissue.
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| 11. |
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| 12. |
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| 13. |
- Aulin, Cecilia, et al.
(författare)
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In situ cross-linkable hyaluronan hydrogel enhances chondrogenesis
- 2011
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Ingår i: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-6254 .- 1932-7005. ; 5:8, s. E188-E196
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Tidskriftsartikel (refereegranskat)abstract
- The present work describes the feasibility of a cross-linkable injectable hyaluronan hydrogel for cartilage repair. The hydrogel used is a two-component system based on aldehyde-modified hyaluronan and hydrazide-modified polyvinyl alcohol, which are rapidly cross-linked in situ upon mixing. The in vitro study showed that chondrocytes and mesenchymal cells cultured in the gel form cartilage-like tissue, rich in glycosaminoglycans, collagen type II and aggrecan. In a rabbit animal model the injection of the hydrogel improved the healing of a full-thickness cartilage defect created in the knee as compared to non-treated controls. This rabbit study showed that the regenerated cartilage defects stained more intensely for type II collagen upon treatment with the hydrogel. The hyaluronan-based hydrogel may be used as a delivery vehicle for both growth factors and/or cells for cartilage repair. The in vivo study also indicated that the hydrogel alone has a beneficial effect on cartilage regeneration.
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| 14. |
- Berg, Jan-Erik, 1957-, et al.
(författare)
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Refining gentleness - a key to bulky CTMP
- 2022
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Ingår i: Nordic Pulp & Paper Research Journal. - : Walter de Gruyter GmbH. - 0283-2631 .- 2000-0669. ; 37:2, s. 349-355
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Tidskriftsartikel (refereegranskat)abstract
- Chemithermomechanical pulp (CTMP) is often used in middle layers of multiply paperboards due to its high bulk at specified strength. Such a CTMP should consist of well-separated undamaged fibres with sufficient bonding capacity. The basic objective of this work is to examine the effect of refining on bulk, taking into account conditions such as temperature, sulphonation, refining gap and refiner size. First stage CTMP made from Norway spruce (Picea abies) were produced in pilot and mill scale trials. Two new parameters, Equivalent temperature related to softness and Refining gentleness are introduced that take into account refining conditions as actual temperature, softening temperature, bound sulphonate content, refining gap and refiner diameter. The results show that bulk increases linearly with refining gentleness.
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| 15. |
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| 16. |
- Bergman, Kristoffer, et al.
(författare)
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Injectable cell-free template for bone-tissue formation
- 2009
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Ingår i: Journal of Biomedical Materials Research-Part A. - : Wiley Periodicals, Inc. - 1549-3296 .- 1552-4965. ; 91A:4, s. 1111-1118
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Tidskriftsartikel (refereegranskat)abstract
- Here we present a novel injectable hydrogel which forms a template for de novo formation of bone tissue. Hydrogel formation takes place in situ in less than 1 min by the cross-linking of multifunctional hyaluronic acid and polyvinyl alcohol derivatives. Endogenous cells are recruited in vivo by incorporating bone morphogenetic protein-2 (BMP-2), a powerful promoter for osteogenic differentiation. The hydrogel was evaluated in vitro by performing a cell viability test and a release study and in vivo by a rat ectopic model. Examination by X-ray, microcomputed tomography, and histology revealed a significant bone formation at the target site for gels containing BMP-2, and a complete degradation was observed for gels without BMP-2 four weeks after injection. There were no signs of inflammation or foreign body response in either group and we believe that this system has the potential as an off-the-shelf injectable to be used where bone tissue is needed.
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| 17. |
- Berthenet, Elvire, et al.
(författare)
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A GWAS on Helicobacter pylori strains points to genetic variants associated with gastric cancer risk
- 2018
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Ingår i: BMC Biology. - : BioMed Central. - 1741-7007. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Helicobacter pylori are stomach-dwelling bacteria that are present in about 50% of the global population. Infection is asymptomatic in most cases, but it has been associated with gastritis, gastric ulcers and gastric cancer. Epidemiological evidence shows that progression to cancer depends upon the host and pathogen factors, but questions remain about why cancer phenotypes develop in a minority of infected people. Here, we use comparative genomics approaches to understand how genetic variation amongst bacterial strains influences disease progression.RESULTS:We performed a genome-wide association study (GWAS) on 173 H. pylori isolates from the European population (hpEurope) with known disease aetiology, including 49 from individuals with gastric cancer. We identified SNPs and genes that differed in frequency between isolates from patients with gastric cancer and those with gastritis. The gastric cancer phenotype was associated with the presence of babA and genes in the cag pathogenicity island, one of the major virulence determinants of H. pylori, as well as non-synonymous variations in several less well-studied genes. We devised a simple risk score based on the risk level of associated elements present, which has the potential to identify strains that are likely to cause cancer but will require refinement and validation.CONCLUSION:There are a number of challenges to applying GWAS to bacterial infections, including the difficulty of obtaining matched controls, multiple strain colonization and the possibility that causative strains may not be present when disease is detected. Our results demonstrate that bacterial factors have a sufficiently strong influence on disease progression that even a small-scale GWAS can identify them. Therefore, H. pylori GWAS can elucidate mechanistic pathways to disease and guide clinical treatment options, including for asymptomatic carriers.
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| 18. |
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| 19. |
- Bugaytsova, Jeanna, et al.
(författare)
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pH regulated H. pylori adherence : implications for persistent infection and disease
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Helicobacter pylori’s BabA adhesin binds strongly to gastric mucosal ABH/Leb glycans on the stomach epithelium and overlying mucus, materials continuously shed into the acidic gastric lumen. Here we report that this binding is acid labile, acid inactivation is fully reversible; and acid lability profiles vary with BabA sequence and correlate with disease patterns. Isogenic H. pylori strains from the gastric antrum and more acidic corpus were identified that differed in acid lability of receptor binding and in sequence near BabA’s carbohydrate binding domain. We propose that reversible acid inactivation of receptor binding helps H. pylori avoid clearance by mucosal shedding, and that strain differences in acid lability affect tissue tropism and the spectrum of associated gastric diseases.
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| 20. |
- Docherty-Skogh, Ann-Charlott, et al.
(författare)
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Bone morphogenetic protein-2 delivered by hyaluronan-based hydrogel induces massive bone formation and healing of cranial defects in minipigs
- 2010
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Ingår i: Plastic and reconstructive surgery (1963). - 0032-1052 .- 1529-4242. ; 125:5, s. 1383-1392
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reconstruction of large craniofacial bone defects is a challenge using bone transplants or alloplastic materials. The use of bone morphogenetic protein (BMP)-2 together with a suitable carrier is an attractive option that may facilitate new bone formation. The authors have developed a hydrogel that is formed in situ by the cross-linking of multifunctional hyaluronic acid and polyvinyl alcohol derivatives mixed with hydroxyapatite nanoparticles, in the presence of BMP-2. The aim of this study was to evaluate the suitability of the hydrogel as a carrier for BMP-2 in repairing critical size cranial defects in a minipig model. Methods: Cranial defects (2 × 4 cm) were created in 14 minipigs. The experimental groups were as follows: group 1, craniotomy and application of 5 ml of hydrogel with 1.25 mg of BMP-2 (n = 6); group 2, craniotomy and application of 5 ml of hydrogel without BMP-2 (n = 6); and group 3, craniotomy with no further treatment (n = 2). Results: After 3 months, computed tomographic and histologic examinations were performed. There was spontaneous ossification in the untreated group, but the healing was incomplete. The hydrogel alone demonstrated no further effects. The addition of 1.25 mg of BMP-2 to the hydrogel induced a greater than 100 percent increase in bone volume (p = 0.003) and complete healing of the defects. Histologic examination revealed compact lamellar bone in the BMP group without intertrabecular fibrous tissue, as was seen in the other groups. The hydrogel was resorbed completely within 3 months and, importantly, caused no inflammatory reaction. Conclusion: The injectable hydrogel may be favorable as a BMP-2 carrier for bone reconstruction.
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| 21. |
- Engstrand, Mats, et al.
(författare)
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Cellular responses to cytomegalovirus in immunosuppressed patients : circulating CD8+ T cells recognizing CMVpp65 are present but display functional impairment
- 2003
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 132:1, s. 96-104
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Tidskriftsartikel (refereegranskat)abstract
- The availability of tetrameric complexes of HLA class I molecules folded with immunodominant peptides makes it possible to utilize flow cytometry for rapid and highly specific visualization of virus specific CD8+ T cells. An alternate technique is to incubate whole blood with specific antigens and to subsequently detect and characterize responding T cells (e.g. by performing intracellular staining of interferon-gamma). By using an HLA-A2 tetramer construct folded with the same immunodominant CMV-peptide as that used for peptide pulsing, we monitored both the presence and functional capacity of CMV-specific CD8+ T cells. In addition T cell activation was assayed by determination of CD38 and CD69 expression. Twelve organ transplant patients and 31 healthy blood donors with latent CMV infection were investigated using CMV pp65 tetramer staining and intracellular staining of interferon-gamma after CMV pp65 peptide pulsing or CMV lysate pulsing. CMV-specific T cells were detected in similar absolute numbers as well as frequencies of T cells in the two groups investigated. However, the CMV-specific CD8+ T cells in immunosuppressed individuals showed a decreased functional response to the CMV-peptide, as evidenced by reduced interferon-gamma production when compared to healthy blood donors (19%; 42%, P < 0·005). In addition, CD38 expression was markedly higher in immunosuppressed patients compared to healthy blood donors (24%; 6%, P < 0·005). In a case report we demonstrate that reactivation of CMV can occur in an immunosuppressed patient with high number of CMV-specific T cells, but without functional capacity. Hence, these findings reflect impaired activation of cytotoxic T cells controlling latent CMV infection in immunosuppressed patients.
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| 22. |
- Engstrand, Mats, et al.
(författare)
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Characterization of CMVpp65-specific CD8+ T lymphocytes using MHC tetramers in kidney transplant patients and healthy participants
- 2000
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 69:11, s. 2243-2250
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cytomegalovirus (CMV) is a ubiquitous herpesvirus that infects 50-90% of individuals in different populations. After primary infection, the virus persists latently in myeloid cells under the control of specific T-cells. Reactivation of CMV infection may cause lethal organ dysfunction and is frequently seen in immunosuppressed individuals. CD8+ cytotoxic T-cells (CTL) have a primary role in suppressing CMV reactivation, and the dominating CTL response is directed against pp65. METHODS: MHC tetramers, that is, complexes between HLA class I (or class II) molecules and antigenic peptides conjugated to fluorochromes allow the direct visualization of antigen-specific receptor-carrying T-cells using flow cytometry. We constructed a novel MHC tetramer for identification of CMVpp65-specific CD8+ T-cells using HLA-A2 molecules folded with the immunodominant NLVPMVATV peptide. RESULTS: The A2/pp65 tetramer specifically stained CMV-directed T-cell lines, and sorted cells showed CMV-specific cytotoxicity. High proportions (0.1-9%) of the CD8+ T-cells were A2/pp65 tetramer+ in healthy HLA-A2+ CMV carriers and in immunosuppressed kidney transplant patients with latent infection. Patients with reactivated CMV infection exhibited up to 15% A2/pp65 tetramer+ cells, which seemed to correlate with CMV load over time. A2/pp65 tetramer+ cells expressed T-cell activation markers. CONCLUSIONS: The construction of a novel A2/pp65 MHC tetramer enabled the design of a rapid and precise flow cytometric method allowing quantitative and qualitative analysis of CMV-specific T-cells. The number of A2/pp65 tetramer binding CTLs in blood may prove to be clinically relevant in assessing the immune response to CMV.
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| 23. |
- Engstrand, Thomas, et al.
(författare)
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A novel biodegradable delivery system for bone morphogenetic protein-2.
- 2008
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Ingår i: Plastic and reconstructive surgery. - 1529-4242. ; 121:6, s. 1920-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The efficacy of recombinant growth factors in vivo is highly dependent on the delivery vehicle. The authors investigated the osteoinductive effects of recombinant human bone morphogenetic proteins (BMP)-2 implanted together with a complex of heparin and chitosan. METHODS: Sixty rats were used. Three different carriers in gel formulation (type I collagen, heparin/type I collagen, and heparin/chitosan) were mixed with either 0, 10, or 50 microg of BMP-2, making the number of groups nine. The gels were injected into the quadriceps muscles of both legs in 45 rats (n = 10 per group). Freeze-dried formulations of the carriers were also tested with the same amounts of BMP-2 using 15 rats (n = 5 per group). Four weeks after implantation, the quality and amount of newly formed bone were assessed. RESULTS: Chitosan was shown to protect the heparinase-mediated degradation of heparin in vitro. The osteoinductive effects of BMP-2 in combination with heparin/chitosan were superior as compared with BMP-2 implanted together with type I collagen. Interestingly, the heparin/chitosan complex induced a small amount of bone also without BMP-2 added. The heparin/chitosan was completely absorbed after 4 weeks as determined by histologic evaluation, and a normal active bone formation was present. The freeze-dried formulations of the carriers demonstrated similar osteoinductive effects as the gels. CONCLUSIONS: An osteoinductive formula for clinical use is needed for general bone reconstruction. Heparin in complex with chitosan has the ability to stabilize or activate the growth factor in vivo and induce the generation of new bone in good yields.
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| 24. |
- Engstrand, Thomas, et al.
(författare)
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Bioceramic Implant Induces Bone Healing of Cranial Defects.
- 2015
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Ingår i: Plastic and reconstructive surgery. Global open. - : LIPPINCOTT WILLIAMS & WILKINS. - 2169-7574. ; 3:8
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Tidskriftsartikel (refereegranskat)abstract
- Autologous bone or inert alloplastic materials used in cranial reconstructions are techniques that are associated with resorption, infection, and implant exposure. As an alternative, a calcium phosphate-based implant was developed and previously shown to potentially stimulate bone growth. We here uncover evidence of induced bone formation in 2 patients. Histological examination 9 months postoperatively showed multinuclear cells in the central defect zone and bone ingrowth in the bone-implant border zone. An increased expression of bone-associated markers was detected. The other patient was investigated 50 months postoperatively. Histological examination revealed ceramic materials covered by vascularized compact bone. The bone regenerative effect induced by the implant may potentially improve long-term clinical outcome compared with conventional techniques, which needs to be verified in a clinical study.
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| 25. |
- Engstrand, Thomas, et al.
(författare)
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Development of a bioactive implant for repair and potential healing of cranial defects
- 2014
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Ingår i: Journal of Neurosurgery. - 0022-3085 .- 1933-0693. ; 120:1, s. 273-277
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Tidskriftsartikel (refereegranskat)abstract
- The repair of complex craniofacial bone defects is challenging and a successful result is dependent on the size of the defect, quality of the soft tissue covering the defect, and choice of reconstruction method. The objective of this study was to develop a bioactive cranial implant that could provide a permanent reconstructive solution to the patient by stimulating bone healing of the defect. In this paper the authors report on the feasibility and clinical results of using such a newly developed device for the repair of a large traumatic and therapy-resistant cranial bone defect. The patient had undergone numerous attempts at repair, in which established methods had been tried without success. A mosaic-designed device was manufactured and implanted, comprising interconnected ceramic tiles with a defined calcium phosphate composition. The clinical outcome 30 months after surgery revealed a restored cranial vault without postoperative complications. Computed tomography demonstrated signs of bone ingrowth. Examination with combined 18F-fluoride PET and CT provided further evidence of bone healing of the cranial defect.
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| 26. |
- Engstrand, Thomas
(författare)
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Molecular regulators in cartilage and bone formation
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cartilage functions as a scaffold for bone formation during development. This process, endochondral ossification, is regulated by systemic hormones and local growth factors. Members of the transforming growth factor-beta (TGF-β) superfamily are essential mediators in cell proliferation and differentiation and play a regulatory role in cartilage and bone formation. The TGF-β superfamily consists of three major subgroups: TGF-β1-3, bone morphogenetic proteins (BMPs), and activins. This thesis presents functional data on TGF-β1 in cartilage formation, BMP2 and BMP3 in bone formation, and a potential role of the BMP-regulatory protein noggin in BMP2 processing. TGF-β1 is found in articular cartilage, stabilizing the chondrocytic phenotype and inhibiting terminal differentiation of chondrocytes. The effect of retrovirally gene-manipulated chondrocytes overexpressing TGF-β1 was investigated. Eight weeks after infection the transgene TGF-β1 was still expressed and the transduced chondrocytes displayed enhanced expression of cartilage-associated matrix molecules. BMP2 possesses the capacity to induce differentiation of osteoprogenitor cells into osteocytes. The gene therapy concept was utilized to assess the osteogenic capacity of osteoprogenitor cells overexpressing BMP2. These cells were capable of differentiating into osteocytes in vitro and formed ectopic bone in vivo. The effect of BMP3 was investigated in cell culture where it counteracted the effects of BMP2. BMP3 was shown to exert its effect through the activin pathway. The effect of BMP3 on bone formation was further demonstrated in mutant mice with targeted deletion of the BMP3 gene. Radiographic and histomorphometric analyses on femurs revealed a higher trabecular bone density in these animals as compared to that in matched wild-type controls. Noggin antagonizes the effects of BMP2 and BMP4 by direct binding. In co-transfection experiments noggin was shown to promote secretion of BMP2. Cells co-expressing BMP2 and noggin displayed an enhanced bone inductive capacity in vitro and in vivo. Noggin may participate in the processing and secretion of BMP2 in addition to inhibiting the mature secreted BMP2 molecule.
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| 27. |
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| 28. |
- Engstrand, Thomas, et al.
(författare)
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Transient production of bone morphogenetic protein 2 by allogeneic transplanted transduced cells induces bone formation
- 2000
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Ingår i: Human Gene Therapy. - 1043-0342 .- 1557-7422. ; 11:1, s. 205-211
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the use of transplantation of genetically modified allogeneic cells as a method to induce bone formation. In this study, we infected a murine osteoprogenitor cell line with a retroviral vector containing the human bone morphogenic protein 2 (BMP2) gene. Transduced cells exhibited more alkaline phosphatase activity than cells treated with any of the tested doses of recombinant human BMP2 protein (rhBMP2). The transduced cells were suspended in a collagen solution and injected into the quadriceps muscle in immunocompetent outbred mice. Radiographic and histological examinations demonstrate abundant ectopic bone formation in 85% of the transplanted animals (n = 13). PCR and Southern blot analysis for the puromycin resistance gene revealed that the transplanted cells were detectable for up to 1 week, but not at later time points. None of the animals developed tumors. Our results suggest that allogeneic BMP2-expressing transduced cells may have therapeutic potential for enhancing new bone formation. This model also provides a simple, inexpensive, and sensitive assay for evaluating in vivo the osteoinductive potentials of secreted proteins without the requirement of protein purification or the use of immunodeficient animals.
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| 29. |
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| 30. |
- Guillet, Claire, et al.
(författare)
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Bone formation beyond the skeletal envelope using calcium phosphate granules packed into a collagen pouch-a pilot study
- 2023
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Ingår i: Biomedical Materials. - : Institute of Physics Publishing (IOPP). - 1748-6041 .- 1748-605X. ; 18:3
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Tidskriftsartikel (refereegranskat)abstract
- In this proof-of-concept, bone neoformation beyond the skeletal envelope is explored by using a collagen pouch (n = 6) packed with calcium phosphate (CaP) granules placed over the frontal bone in sheep (n = 3). At 13 weeks, macroscopic examination showed specimens covered by an adherent fibrinous envelope with slight vascularization. Histology revealed colonization of the implant by newly formed woven bone and fibrous connective tissue. Surface osteoblasts as well as material-filled macrophages, lymphocytes, polymorphonuclear cells and giant cells were also found in large quantities surrounding the newly formed bone tissue inside the collagen pouch. On the side facing the recipient bone, the collagen membrane had to a large extent been resorbed and bridging bone formation was clearly visible between the test article and recipient bone. On the other side facing soft tissue, the collagen pouch remained intact with a visible fibrous capsule. This study demonstrated that the use of a collagen sleeve as a container for CaP granules allows for good neoformation beyond the skeletal envelope with bridging bone formation clearly visible between the test article and recipient bone. Additionally, in this model, macrophages rather than osteoclasts appear to modulate CaP granule resorption and remodeling into new bone. This construct opens new perspectives for treatment methods that could be used for bone augmentation and restoration of cranio-maxillofacial defects and malformations.
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| 31. |
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| 32. |
- Hilborn, Jöns, et al.
(författare)
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Preparing Bone Using an Injectable Hydrogel Scaffold
- 2008
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Ingår i: TERMIS EU 2008 Porto Meeting June 22–26, 2008 Porto Congress Center–Alfândega Portugal. - : Mary Ann Liebert Inc.. ; , s. 769-770
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 33. |
- Hober, Andreas, et al.
(författare)
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Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis
- 2021
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Ingår i: eLIFE. - : eLIFE SCIENCES PUBL LTD. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Reliable, robust, large-scale molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for monitoring the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a scalable analytical approach to detect viral proteins based on peptide immuno-affinity enrichment combined with liquid chromatography-mass spectrometry (LC-MS). This is a multiplexed strategy, based on targeted proteomics analysis and read-out by LC-MS, capable of precisely quantifying and confirming the presence of SARS-CoV-2 in phosphate-buffered saline (PBS) swab media from combined throat/nasopharynx/saliva samples. The results reveal that the levels of SARS-CoV-2 measured by LC-MS correlate well with their correspondingreal-time polymerase chain reaction (RT-PCR) read-out (r = 0.79). The analytical workflow shows similar turnaround times as regular RT-PCR instrumentation with a quantitative read-out of viral proteins corresponding to cycle thresholds (Ct) equivalents ranging from 21 to 34. Using RT-PCR as a reference, we demonstrate that the LC-MS-based method has 100% negative percent agreement (estimated specificity) and 95% positive percent agreement (estimated sensitivity) when analyzing clinical samples collected from asymptomatic individuals with a Ct within the limit of detection of the mass spectrometer (Ct <= 30). These results suggest that a scalable analytical method based on LC-MS has a place in future pandemic preparedness centers to complement current virus detection technologies.
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| 34. |
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| 35. |
- Ibrahim, Ahmed, et al.
(författare)
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Colitis-induced colorectal cancer and intestinal epithelial estrogen receptor beta impact gut microbiota diversity
- 2019
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 144:12, s. 3086-3098
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Tidskriftsartikel (refereegranskat)abstract
- Chronic inflammation of the colon (colitis) is a risk factor for colorectal cancer (CRC). Hormone-replacement therapy reduces CRC incidences, and the estrogen receptor beta (ERβ/ESR2) has been implicated in this protection. Gut microbiota is altered in both colitis and CRC and may influence the severity of both. Here we test the hypothesis that intestinal ERβ impacts the gut microbiota. Mice with and without intestine-specific deletion of ERβ (ERβKOVil ) were generated using the Cre-LoxP system. Colitis and CRC were induced with a single intraperitoneal injection of azoxymethane (AOM) followed by administration of three cycles of dextran sulfate sodium (DSS) in drinking water. The microbiota population were characterized by high-throughput 16S rRNA gene sequencing of DNA extracted from fecal samples (N = 39). Differences in the microbiota due to AOM/DSS and absence of ERβ were identified through bioinformatic analyses of the 16S-Seq data, and the distribution of bacterial species was corroborated using qPCR. We demonstrate that colitis-induced CRC reduced the gut microbiota diversity and that loss of ERβ enhanced this process. Further, the Bacteroidetes genus Prevotellaceae_UCG_001 was overrepresented in AOM/DSS mice compared to untreated controls (3.5-fold, p = 0.004), and this was enhanced in females and in ERβKOVil mice. Overall, AOM/DSS enriched for microbiota impacting immune system diseases and metabolic functions, and lack of ERβ in combination with AOM/DSS enriched for microbiota impacting carbohydrate metabolism and cell motility, while reducing those impacting the endocrine system. Our data support that intestinal ERβ contributes to a more favorable microbiome that could attenuate CRC development.
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| 36. |
- Ilver, D, et al.
(författare)
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Helicobacter pylori adhesin binding fucosylated histo-blood group antigens revealed by retagging
- 1998
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 279:5349, s. 373-377
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Tidskriftsartikel (refereegranskat)abstract
- The bacterium Helicobacter pylori is the causative agent for peptic ulcer disease. Bacterial adherence to the human gastric epithelial lining is mediated by the fucosylated Lewis b (Leb) histo-blood group antigen. The Leb-binding adhesin, BabA, was purified by receptor activity-directed affinity tagging. The bacterial Leb-binding phenotype was associated with the presence of the cag pathogenicity island among clinical isolates of H. pylori. A vaccine strategy based on the BabA adhesin might serve as a means to target the virulent type I strains of H. pylori.
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| 37. |
- Jakobsson, Hedvig E., et al.
(författare)
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Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section
- 2014
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Ingår i: Gut. - London : BMJ. - 0017-5749 .- 1468-3288. ; 63:4, s. 559-566
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Tidskriftsartikel (refereegranskat)abstract
- important stimuli for immune development, and a reduced microbial exposure as well as caesarean section (CS) has been associated with the development of allergic disease. Here we address how microbiota development in infants is affected by mode of delivery, and relate differences in colonisation patterns to the maturation of a balanced Th1/Th2 immune response. Design The postnatal intestinal colonisation pattern was investigated in 24 infants, born vaginally (15) or by CS (nine). The intestinal microbiota were characterised using pyrosequencing of 16S rRNA genes at 1 week and 1, 3, 6, 12 and 24 months after birth. Venous blood levels of Th1- and Th2-associated chemokines were measured at 6, 12 and 24 months. Results Infants born through CS had lower total microbiota diversity during the first 2 years of life. CS delivered infants also had a lower abundance and diversity of the Bacteroidetes phylum and were less often colonised with the Bacteroidetes phylum. Infants born through CS had significantly lower levels of the Th1-associated chemokines CXCL10 and CXCL11 in blood. Conclusions CS was associated with a lower total microbial diversity, delayed colonisation of the Bacteroidetes phylum and reduced Th1 responses during the first 2 years of life.
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| 38. |
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| 39. |
- Kihlström Burenstam Linder, Lars, et al.
(författare)
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Patient-Specific Titanium-Reinforced Calcium Phosphate Implant for the Repair and Healing of Complex Cranial Defects
- 2019
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Ingår i: World Neurosurgery. - : ELSEVIER SCIENCE INC. - 1878-8750 .- 1878-8769. ; 122, s. E399-E407
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The reconstruction of complex cranial defects is challenging and is associated with a high complication rate. The development of a patient-specific, titanium-reinforced, calcium phosphate-based (CaP-Ti) implant with bone regenerative properties has previously been described in 2 case studies with the hypothesis that the implant may improve clinical outcome. OBJECTIVE: To identify whether the introduction of CaP-Ti implant has the potential to improve clinical outcome. METHODS: A retrospective review of all patients having undergone CaP-Ti cranioplasty was conducted. Comprehensive clinical data were collected from the hospital computer database and patient records. Bone formation and osseointegration were analyzed in a single retrieval specimen. RESULTS: Fifty patients, with 52 cranial defects, met the inclusion criteria. The patient cohort displayed a previous failure rate of 64% (32/50) with autologous bone, alloplastic materials, or both. At a median follow-up time of 25 months, the explantation rate due to either early postoperative infection or persistent wound dehiscence was 1.9% (1/53) or 3.8% (2/53), respectively. Surgical intervention with local wound revision was required in 2 patients without the need of implant removal. One patient had a brain tumor recurrence, and the implant was explanted 31 months after implantation. Histologic examination showed that the entire implant was partly yet evenly transformed into vascularized compact bone. CONCLUSION: In the present study the CaP-Ti implant appears to have improved the clinical outcomes in a cohort of patients with a high rate of previous cranioplasty failures. The bone regenerative effect may in particular have an impact on the long-term success rate of the implant.
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| 40. |
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| 41. |
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| 42. |
- Marabita, Francesco, et al.
(författare)
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Multiomics and digital monitoring during lifestyle changes reveal independent dimensions of human biology and health
- 2022
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Ingår i: Cell Systems. - : Cell Press. - 2405-4712 .- 2405-4720. ; 13:3, s. 241-255.e7
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Tidskriftsartikel (refereegranskat)abstract
- We explored opportunities for personalized and predictive health care by collecting serial clinical measurements, health surveys, genomics, proteomics, autoantibodies, metabolomics, and gut microbiome data from 96 individuals who participated in a data-driven health coaching program over a 16-month period with continuous digital monitoring of activity and sleep. We generated a resource of >20,000 biological samples from this study and a compendium of >53 million primary data points for 558,032 distinct features. Multiomics factor analysis revealed distinct and independent molecular factors linked to obesity, diabetes, liver function, cardiovascular disease, inflammation, immunity, exercise, diet, and hormonal effects. For example, ethinyl estradiol, a common oral contraceptive, produced characteristic molecular and physiological effects, including increased levels of inflammation and impact on thyroid, cortisol levels, and pulse, that were distinct from other sources of variability observed in our study. In total, this work illustrates the value of combining deep molecular and digital monitoring of human health. A record of this paper's transparent peer review process is included in the supplemental information.
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| 43. |
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| 44. |
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| 45. |
- Nageeb, Mohamad, et al.
(författare)
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Bone Engineering by Biomimetic Injectable Hydrogel
- 2012
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Ingår i: Molecular Crystals and Liquid Crystals. - : Informa UK Limited. - 1542-1406 .- 1563-5287. ; 555:1, s. 177-188
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Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis is a multifactorial bone disease characterized by low bone mineral density (BMD) and deterioration of micro-architecture of cancellous bone leading to bone fragility and risk of fractures. In the current work, a novel tissue engineering strategy was experimented to enhance bone architecture in the risk areas via local injection of a biomimetic/osteoinductive injectable hyaluronan based hydrogel loaded with nano-hydroxyapatite crystals (Hya/HA) with/without bone morphogenetic protein (BMP-2), in distal femur of normal and ovariectomized New Zealand white rabbits. Our results revealed the osteoinductive effect of the Hya/HA composite that enhanced bone density and architecture of the rabbit distal femur.
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| 46. |
- Nelsson, E., et al.
(författare)
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Mill scale production of TMP with double disk refining-The effects of a mild sulfonation, atmospheric preheating and refining temperatures
- 2016
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Ingår i: International Mechanical Pulping Conference 2016, IMPC 2016. - : TAPPI Press. - 9781510830738 ; , s. 249-259
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Konferensbidrag (refereegranskat)abstract
- The aim of this work was to study the effects of a mild dosage of sodium sulfite in chip impregnation at diffen temperatures during atmospheric preheating and during refining for production of TMP for printing papers usi high intensity double disk refining. Two trials were performed in the 800 bdt/day double disc line at I Braviken paper mill (Holmen Paper AB, Sweden) using Norway spruce chips. During the trials, chips w( impregnated in an Impressafiner where chips were preheated at 1.8 bar(g) for a few seconds and th compressed before impregnation. During impregnation, sodium sulfite was added to chips at pH 9 in dosages 0.6 or 1.2%. Reference pulps without addition of sulfite were also produced. In the first trial, the effect different temperatures and retention times (80°C for 6 minutes vs. 96°C for 9 minutes) in the atmosphe preheating bin following impregnation was evaluated both with and without the addition of 1.2% sodium sulf In the second trial, the effect of different refining temperatures (refiner house pressures of 4.6 or 6.4 bar(g), 1 or 167°C) was evaluated with different additions of sodium sulfite (0.0, 0.6 or 1,2%) during impregnation. The results from the two trials showed that the increase in refiner house pressure increased the tensile index pulps both with and without addition of sodium sulfite, when compared at certain SEC. However, the increase preheater bin temperature and retention time did not increase the tensile index of pulps but rather led to a sm reduction in tensile index when combined with an addition of 1.2% sodium sulfite. The two different methc used to increase the temperature in the system led to different effects in the disc gap at certain SEC. The disc j temperature was increased by both methods but disc gap was only reduced at certain SEC when the refini temperature was increased by increasing the refiner housing pressure. The difference in the effect on the disc j may hold the answer to the different effects seen in tensile index.
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| 47. |
- Norlin, Börje, associate professor, 1967-, et al.
(författare)
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Visualisation of sulphur on single fibre level for pulping industry
- 2023
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Ingår i: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 18:01, s. C01012-C01012
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Tidskriftsartikel (refereegranskat)abstract
- In the pulp and paper industry, about 5 Mt/y chemithermomechanical pulp (CTMP) are produced globally from softwood chips for production of carton board grades. For tailor making CTMP for this purpose, wood chips are impregnated with aqueous sodium sulphite for sulphonation of the wood lignin. When lignin is sulphonated, the defibration of wood into pulp becomes more selective, resulting in enhanced pulp properties. On a microscopic fibre scale, however, one could strongly assume that the sulphonation of the wood structure is very uneven due to its macroscale size of wood chips. If this is the case and the sulphonation could be done significantly more evenly, the CTMP process could be more efficient and produce pulp even better suited for carton boards. Therefore, the present study aimed to develop a technique based on X-ray fluorescence microscopy imaging (µXRF) for quantifying the sulphur distribution on CTMP wood fibres. Firstly, the feasibility of µXRF imaging for sulphur homogeneity measurements in wood fibres needs investigation. Therefore, clarification of which spatial and spectral resolution that allows visualization of sulphur impregnation into single wood fibres is needed. Measurements of single fibre imaging were carried out at the Argonne National Laboratory’s Advanced Photon Source (APS) synchrotron facility. With a synchrotron beam using one micrometre scanning step, images of elemental mapping are acquired from CTMP samples diluted with non-sulphonated pulp under specified conditions. Since the measurements show significant differences between sulphonated and non-sulphonated fibres, and a significant peak concentration in the shell of the sulphonated fibres, the proposed technique is found to be feasible. The required spatial resolution of the µXRF imaging for an on-site CTMP sulphur homogeneity measurement setup is about 15 µm, and the homogeneity measured along the fibre shells is suggested to be used as the CTMP sulphonation measurement parameter.
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| 48. |
- Nowinski, Daniel, et al.
(författare)
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Keratinocytes inhibit expression of connective tissue growth factor in fibroblasts in vitro by an interleukin-1alpha dependent mecanism
- 2002
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Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 119:2, s. 449-455
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Tidskriftsartikel (refereegranskat)abstract
- The wound healing process concludes with downregulation of fibroblast activity. Clinical observations suggest that the regenerating epidermis suppresses this activity. An important regulator of fibroblast activity is the fibrogenic cytokine connective tissue growth factor. We hypothesized that epidermal keratinocytes may affect fibroblast activity via this cytokine. We demonstrate keratinocyte-mediated suppression of connective tissue growth factor at both the mRNA and protein levels by around 50% or more when fibroblasts were cultured in multiwell plates with keratinocyte cultures in accompanying semipermeable cell culture inserts, or stimulated by keratinocyte-conditioned media. Both basal and transforming-growth-factor-beta1-stimulated levels of connective tissue growth factor were inhibited. A 3 h coculture period with keratinocytes was sufficient to suppress connective tissue growth factor expression by fibroblasts, but the inhibition developed over a time period of around 16 h. The putative keratinocyte-derived factor(s) responsible for these effects was found to be soluble and stable. By analyzing cytokines secreted by keratinocytes we identified interleukin-1alpha as a potent inhibitor of connective tissue growth factor mRNA expression in fibroblasts. Involvement of this cytokine in keratinocyte-mediated connective tissue growth factor suppression was confirmed by using anti-interleukin-1alpha antibodies. Tumor necrosis factor alpha or prostaglandins did not appear to be involved. In conclusion, our results indicate that interleukin-1alpha secretion by keratinocytes provides a mechanism for the downregulation of connective tissue activity during the end-stage of wound healing, when epithelia coverage has developed over the wound area.
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| 49. |
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| 50. |
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