| 1. |
- Cano, María Emilia, et al.
(författare)
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Characterization of carboxylated cellulose nanofibrils and oligosaccharides from Kraft pulp fibers and their potential elicitor effect on the gene expression of Capsicum annuum
- 2024
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Ingår i: International Journal of Biological Macromolecules. - : Elsevier B.V.. - 0141-8130 .- 1879-0003. ; 267
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Tidskriftsartikel (refereegranskat)abstract
- Biomass-derived oligo- and polysaccharides may act as elicitors, i.e., bioactive molecules that trigger plant immune responses. This is particularly important to increase the resistance of plants to abiotic and biotic stresses. In this study, cellulose nanofibrils (CNF) gels were obtained by TEMPO-mediated oxidation of unbleached and bleached kraft pulps. The molecular structures were characterized with ESI and MALDI MS. Analysis of the fine sequences was achieved by MS and MS/MS of the water-soluble oligosaccharides obtained by acid hydrolysis of the CNF gels. The analysis revealed the presence of two families: one corresponding to homoglucuronic acid sequences and the other composed by alternating glucose and glucuronic acid units. The CNF gels, alone or with the addition of the water-soluble oligosaccharides, were tested on Chili pepper (Capsicum annuum). Based on the characterization of the gene expression with Next Generation Sequencing (NGS) of the C. annuum’s total messenger RNA, the differences in growth of the C. annuum seeds correlated well with the downregulation of the pathways regulating photosynthesis. A downregulation of the response to abiotic factors was detected, suggesting that these gels would improve the resistance of the C. annuum plants to abiotic stress due to, e.g., water deprivation and cold temperatures.
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| 2. |
- Chinga Carrasco, Gary, et al.
(författare)
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Carboxylated nanocellulose for wound healing applications – Increase of washing efficiency after chemical pre-treatment and stability of homogenized gels over 10 months
- 2023
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Ingår i: Carbohydrate Polymers. - : Elsevier Ltd. - 0144-8617 .- 1879-1344. ; 314
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Tidskriftsartikel (refereegranskat)abstract
- To commercialize a biomedical product as a medical device, reproducibility of production and time-stability are important parameters. Studies of reproducibility are lacking in the literature. Additionally, chemical pre-treatments of wood fibres to produce highly fibrillated cellulose nanofibrils (CNF) seem to be demanding in terms of production efficiency, being a bottleneck for industrial upscaling. In this study, we evaluated the effect of pH on the dewatering time and washing steps of 2,2,6,6-Tetramethylpiperidinyloxy (TEMPO)-mediated oxidized wood fibres when applying 3.8 mmol NaClO/g cellulose. The results indicate that the method does not affect the carboxylation of the nanocelluloses, and levels of approximately 1390 μmol/g were obtained with good reproducibility. The washing time of a Low-pH sample was reduced to 1/5 of the time required for washing a Control sample. Additionally, the stability of the CNF samples was assessed over 10 months and changes were quantified, the most pronounced were the increase of potential residual fibre aggregates, reduction of viscosity and increase of carboxylic acid content. The cytotoxicity and skin irritation potential were not affected by the detected differences between the Control and Low-pH samples. Importantly, the antibacterial effect of the carboxylated CNFs against S. aureus and P. aeruginosa was confirmed. © 2023 The Authors
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| 3. |
- Chinga-Carrasco, Gary, et al.
(författare)
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Nanocelluloses – Nanotoxicology, Safety Aspects and 3D Bioprinting
- 2022
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Ingår i: Advances in Experimental Medicine and Biology. - Cham : Springer. - 0065-2598 .- 2214-8019. ; 1357, s. 155-177
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Tidskriftsartikel (refereegranskat)abstract
- Nanocelluloses have good rheological properties that facilitate the extrusion of nanocellulose gels in micro-extrusion systems. It is considered a highly relevant characteristic that makes it possible to use nanocellulose as an ink component for 3D bioprinting purposes. The nanocelluloses assessed in this book chapter include wood nanocellulose (WNC), bacterial nanocellulose (BNC), and tunicate nanocellulose (TNC), which are often assumed to be non-toxic. Depending on various chemical and mechanical processes, both cellulose nanofibrils (CNF) and cellulose nanocrystals (CNC) can be obtained from the three mentioned nanocelluloses (WNC, BNC, and TNC). Pre/post-treatment processes (chemical and mechanical) cause modifications regarding surface chemistry and nano-morphology. Hence, it is essential to understand whether physicochemical properties may affect the toxicological profile of nanocelluloses. In this book chapter, we provide an overview of nanotoxicology and safety aspects associated with nanocelluloses. Relevant regulatory requirements are considered. We also discuss hazard assessment strategies based on tiered approaches for safety testing, which can be applied in the early stages of the innovation process. Ensuring the safe development of nanocellulose-based 3D bioprinting products will enable full market use of these sustainable resources throughout their life cycle.
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| 4. |
- Granskog, Viktor, et al.
(författare)
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High-Performance Thiol–Ene Composites Unveil a New Era of Adhesives Suited for Bone Repair
- 2018
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Ingår i: Advanced Functional Materials. - : Wiley. - 1616-301X .- 1616-3028. ; 28:26
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Tidskriftsartikel (refereegranskat)abstract
- The use of adhesives for fracture fixation can revolutionize the surgical procedures toward more personalized bone repairs. However, there are still no commercially available adhesive solutions mainly due to the lack of biocompatibility, poor adhesive strength, or inadequate fixation protocols. Here, a surgically realizable adhesive system capitalizing on visible light thiol–ene coupling chemistry is presented. The adhesives are carefully designed and formulated from a novel class of chemical constituents influenced by dental resin composites and self-etch primers. Validation of the adhesive strength is conducted on wet bone substrates and accomplished via fiber-reinforced adhesive patch (FRAP) methodology. The results unravel, for the first time, on the promise of a thiol–ene adhesive with an unprecedented shear bond strength of 9.0 MPa and that surpasses, by 55%, the commercially available acrylate dental adhesive system Clearfil SE Bond of 5.8 MPa. Preclinical validation of FRAPs on rat femur fracture models details good adhesion to the bone throughout the healing process, and are found biocompatible not giving rise to any inflammatory response. Remarkably, the FRAPs are found to withstand loads up to 70 N for 1000 cycles on porcine metacarpal fractures outperforming clinically used K-wires and match metal plates and screw implants.
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| 5. |
- Håkansson, Joakim, 1975, et al.
(författare)
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Changes in ion-channels in the dorsal root ganglion after exposure to autologous nucleus pulposus and TNF. A rat experimental study
- 2024
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Ingår i: Journal of Orthopaedics. - : Reed Elsevier India Pvt. Ltd.. - 0972-978X .- 2589-9082. ; 47, s. 23-27
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: It is known that contact of nucleus pulposus with the dorsal root ganglion may induce changes in nerve conduction and pain behavior. It has also been suggested that the behavioristic changes are caused by changes in voltage-gated ion channels, which in turn have been upregulated by TNF. Such upregulations have previously been shown for NaV 1.8 and NaV 1.9. In this investigation, we expanded the number of studied ion channels after the application of nucleus pulposus or TNF. Methods: Following removal of the left L4-5 fact joint, a disc puncture was performed and the dorsal root ganglion was exposed to nucleus pulposus (n = 5) and TNF (n = 5). Operated rats without disc puncture served as sham (n = 5) and 5 non-operated (naïve) rats were included. After 24 h, the DRGs were harvested and analyzed by quantitative PCR on validated pre-spotted primer plates displaying genes for 90 voltage-gated ion channels. Results: It was evident that the changes in operated animals were separate from the naïve rats. It was also apparent that gene expression changes in rats with nucleus pulposus or TNF application showed similar trends and were also separated from sham-operated animals. Conclusion: The application of nucleus pulposus and TNF onto the DRG in rats induces comparable changes in gene expression of several ion channels. Since the changes induced by TNF and NP are similar, one might also suspect that TNF mediates the NP-induced changes. However, such a mechanism needs further investigation.
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| 6. |
- Landberg, Göran, 1963, et al.
(författare)
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Characterization of cell-free breast cancer patient-derived scaffolds using liquid chromatography-mass spectrometry/mass spectrometry data and RNA sequencing data
- 2020
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Ingår i: Data in Brief. - : Elsevier BV. - 2352-3409. ; 31
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Tidskriftsartikel (refereegranskat)abstract
- Patient-derived scaffolds (PDSs) generated from primary breast cancer tumors can be used to model the tumor microenvironment in vitro . Patient-derived scaffolds are generated by repeated detergent washing, removing all cells. Here, we analyzed the protein composition of 15 decellularized PDSs using liquid chromatography-mass spectrometry/mass spectrometry. One hundred forty-three proteins were detected and their relative abundance was calculated using a reference sample generated from all PDSs. We performed heatmap analysis of all the detected proteins to display their expression patterns across different PDSs together with pathway enrichment analysis to reveal which processes that were connected to PDS protein composition. This protein dataset together with clinical information is useful to investigators studying the microenvironment of breast cancers. Further, after repopulating PDSs with either MCF7 or MDA-MB-231 cells, we quantified their gene expression profiles using RNA sequencing. These data were also compared to cells cultured in conventional 2D conditions, as well as to cells cultured as xenografts in immune-deficient mice. We investigated the overlap of genes regulated between these different culture conditions and performed pathway enrichment analysis of genes regulated by both PDS and xenograft cultures compared to 2D in both cell lines to describe common processes associated with both culture conditions. Apart from our described analyses of these systems, these data are useful when comparing different experimental model systems. Downstream data analyses and interpretations can be found in the research article "Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment" [1] . (C) 2020 The Authors. Published by Elsevier Inc.
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| 7. |
- Landberg, Göran, et al.
(författare)
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Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment
- 2020
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Ingår i: Biomaterials. - : Elsevier Ltd. - 0142-9612 .- 1878-5905. ; 235
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Tidskriftsartikel (refereegranskat)abstract
- Tumor cells interact with the microenvironment that specifically supports and promotes tumor development. Key components in the tumor environment have been linked to various aggressive cancer features and can further influence the presence of subpopulations of cancer cells with specific functions, including cancer stem cells and migratory cells. To model and further understand the influence of specific microenvironments we have developed an experimental platform using cell-free patient-derived scaffolds (PDSs) from primary breast cancers infiltrated with standardized breast cancer cell lines. This PDS culture system induced a series of orchestrated changes in differentiation, epithelial-mesenchymal transition, stemness and proliferation of the cancer cell population, where an increased cancer stem cell pool was confirmed using functional assays. Furthermore, global gene expression profiling showed that PDS cultures were similar to xenograft cultures. Mass spectrometry analyses of cell-free PDSs identified subgroups based on their protein composition that were linked to clinical properties, including tumor grade. Finally, we observed that an induction of epithelial-mesenchymal transition-related genes in cancer cells growing on the PDSs were significantly associated with clinical disease recurrences in breast cancer patients. Patient-derived scaffolds thus mimics in vivo-like growth conditions and uncovers unique information about the malignancy-inducing properties of tumor microenvironment. © 2019 The Authors
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| 8. |
- Pasquier, Eva, et al.
(författare)
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Polysaccharides and Structural Proteins as Components in Three-Dimensional Scaffolds for Breast Cancer Tissue Models: A Review
- 2023
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Ingår i: Bioengineering. - : MDPI. - 2306-5354. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer is the most common cancer among women, and even though treatments are available, efficiency varies with the patients. In vitro 2D models are commonly used to develop new treatments. However, 2D models overestimate drug efficiency, which increases the failure rate in later phase III clinical trials. New model systems that allow extensive and efficient drug screening are thus required. Three-dimensional printed hydrogels containing active components for cancer cell growth are interesting candidates for the preparation of next generation cancer cell models. Macromolecules, obtained from marine- and land-based resources, can form biopolymers (polysaccharides such as alginate, chitosan, hyaluronic acid, and cellulose) and bioactive components (structural proteins such as collagen, gelatin, and silk fibroin) in hydrogels with adequate physical properties in terms of porosity, rheology, and mechanical strength. Hence, in this study attention is given to biofabrication methods and to the modification with biological macromolecules to become bioactive and, thus, optimize 3D printed structures that better mimic the cancer cell microenvironment. Ink formulations combining polysaccharides for tuning the mechanical properties and bioactive polymers for controlling cell adhesion is key to optimizing the growth of the cancer cells.
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| 9. |
- Rosendahl, Jennifer, et al.
(författare)
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3D printed nanocellulose scaffolds as a cancer cell culture model system
- 2021
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Ingår i: Bioengineering. - : MDPI AG. - 2306-5354. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Current conventional cancer drug screening models based on two-dimensional (2D) cell culture have several flaws and there is a large need of more in vivo mimicking preclinical drug screening platforms. The microenvironment is crucial for the cells to adapt relevant in vivo characteristics and here we introduce a new cell culture system based on three-dimensional (3D) printed scaffolds using cellulose nanofibrils (CNF) pre-treated with 2,2,6,6-tetramethylpyperidine-1-oxyl (TEMPO) as the structural material component. Breast cancer cell lines, MCF7 and MDA-MB-231, were cultured in 3D TEMPO-CNF scaffolds and were shown by scanning electron microscopy (SEM) and histochemistry to grow in multiple layers as a heterogenous cell population with different morphologies, contrasting 2D cultured mono-layered cells with a morphologically homogenous cell population. Gene expression analysis demonstrated that 3D TEMPO-CNF scaffolds induced elevation of the stemness marker CD44 and the migration markers VIM and SNAI1 in MCF7 cells relative to 2D control. T47D cells confirmed the increased level of the stemness marker CD44 and migration marker VIM which was further supported by increased capacity of holoclone formation for 3D cultured cells. Therefore, TEMPO-CNF was shown to represent a promising material for 3D cell culture model systems for cancer cell applications such as drug screening. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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| 10. |
- Rosendahl, Jennifer
(författare)
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3D Printed scaffolds as cancer microenvironment medels for drug discovery
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer is one of the most common diseases in the modern world and major efforts are made globally to develop new diagnostics and treatments. It originates from a cell which, at some point, has begun to divide and grow uncontrollably. The most common type is breast cancer, and like all other cancers there is a need of more efficient drug therapies. Drug development is an expensive and time-consuming process and in conventional pre-clinical evaluation, drugs are tested on cells grown in 2D followed by experimental studies in animals. Only the drug candidates with best efficacy and safety profiles are allowed to proceed to clinical trials in humans. A major problem is that the pre-clinical test methods most often do not adequately represent the microenvironment in the human body and only a portion of the drugs that show good effect in pre-clinical studies pass the clinical trials and reaches market. Failures in late development mean large losses both financially and in time, and better pre-clinical test methods are needed that can predict more accurate results for safety and efficacy. The behavior of cancer cells is strongly influenced by the surrounding microenvironment, but today’s drug development focuses mainly on the cells themselves and does not sufficiently take this into account. This thesis combines 3D printing and cell biology to develop new and more representative test systems, with the ambition to mimic the tumor microenvironment in three dimensions. By using patient tumor tissue and removing the original cells, we produce a cell-free extracellular matrix scaffold to which standardized reporter breast cancer cell lines are reintroduced. The cell lines grown in the patient derived scaffolds developed more stem cell properties and formed a more heterogeneous cell population compared to 2D cultures. Moreover, the gene expression profile could be linked to clinical data, such as relapse. In an attempt to synthetically mimic the human tumor tissue, we used an alginate-based biomaterial to print 3D scaffolds. Breast cancer cells cultured in the 3D printed scaffolds showed a more similar growth- and gene expression pattern to cells cultured in patient derived scaffolds indicating that we were able to simulate the human tumor microenvironment. Further, we showed that the cells cultured in both patient derived scaffolds and 3D printed scaffolds had a similar response to hypoxic conditions – which is an important factor in tumors. Finally, we also showed that nanocellulose could be used to 3D print and that cells cultured in these scaffolds demonstrated comparable results to cells grown in alginate-based 3D printed scaffolds.
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