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Sökning: AMNE:(TEKNIK OCH TEKNOLOGIER Industriell bioteknik Bioteknisk apparatteknik)

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1.
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2.
  • Apelgren, Peter, et al. (författare)
  • Vascularization of tissue engineered cartilage-Sequential in vivo MRI display functional blood circulation
  • 2021
  • Ingår i: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 276
  • Tidskriftsartikel (refereegranskat)abstract
    • Establishing functional circulation in bioengineered tissue after implantation is vital for the delivery of oxygen and nutrients to the cells. Native cartilage is avascular and thrives on diffusion, which in turn depends on proximity to circulation. Here, we investigate whether a gridded three-dimensional (3D) bioprinted construct would allow ingrowth of blood vessels and thus prove a functional concept for vascularization of bioengineered tissue. Twenty 10 x 10 x 3-mm 3Dbioprinted nanocellulose constructs containing human nasal chondrocytes or cell-free controls were subcutaneously implanted in 20 nude mice. Over the next 3 months, the mice were sequentially imaged with a 7 T small-animal MRI system, and the diffusion and perfusion parameters were analyzed. The chondrocytes survived and proliferated, and the shape of the constructs was well preserved. The diffusion coefficient was high and well preserved over time. The perfusion and diffusion patterns shown by MRI suggested that blood vessels develop over time in the 3D bioprinted constructs; the vessels were confirmed by histology and immunohistochemistry. We conclude that 3D bioprinted tissue with a gridded structure allows ingrowth of blood vessels and has the potential to be vascularized from the host. This is an essential step to take bioengineered tissue from the bench to clinical practice.
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3.
  • Muzamal, Muhammad, 1986 (författare)
  • Steam Explosion of Wood
  • 2014
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The rising price of petroleum and environmental concerns regarding CO2 emissions has increased interest in alternative renewable resources. Biomass can be considered as an excellent alternative raw material. A biorefinery uses biomass and produces fuel, energy and value-added chemicals. The biorefinery is an emerging field and requires much development to compete with already established petroleum-based industries. One of the greatest challenges to the biorefinery is that the raw material; biomass, has a complex chemical composition and physical structure. A pretreatment process is necessary to induce physico-chemical changes in the biomass and transform it into easily digestible material. The main factor limiting enzymatic digestion of biomass is accessibility to chemical constituents. Steam Explosion (SE) pretreatment is a promising process that has many potential benefits compared to the alternatives, e.g. it has less hazardous process chemicals and conditions, less environmental impact, fewer energy requirements and lower capital investment.Existing literature on the SE process mainly concerns products obtained after the process. Knowledge about the physical processes that take place during the SE pretreatment is limited. This licentiate thesis is based on experimental and modelling studies performed with the aim of gaining knowledge of the basic mechanisms of this process. The SE is a three-step process that involves; (i) treatment of wood with pressurized steam for a specific period of time, (ii) explosion of wood chips through the rapid release of pressure, and (iii) impact of softened wood chips with other chips and vessel walls. In the experimental part these steps have been carefully isolated and the effects of these steps on internal and external structures of single spruce wood pieces have been studied. The effect of vapour expansion and the creation of stresses during the explosion step on a single cell of spruce wood (with four layers; P, S1, S2 and S3) at high temperature and moisture content have been modelled using the Finite Element Method.The study reveals that all the steps of the SE process contribute to structural changes in the wood material and increase pore size which increases the accessibility of chemical reagents and enzymes. A wood piece disintegrates into smaller pieces during the impact step. The vapour expansion inside cells during the explosion step causes each cell to expand in all directions and creates high stress and strain fields perpendicular to the cell direction. In general, cell wall damage is more likely to occur in cells with thin walls, i.e. earlywood; damaged P, S1 and S3 layers; low MFAs; irregular cross-sections and sharp corners.
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4.
  • Ortiz Catalan, Max Jair, 1982, et al. (författare)
  • Self-Contained Neuromusculoskeletal Arm Prostheses
  • 2020
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:18, s. 1732-1738
  • Tidskriftsartikel (refereegranskat)abstract
    • After transhumeral amputation, four patients had implantation of a self-contained, osseointegrated prosthesis with a neuromusculoskeletal interface that allowed intuitive control of the prosthetic hand and arm over 3 to 7 years. A video shows use of the prostheses in daily life. We report the use of a bone-anchored, self-contained robotic arm with both sensory and motor components over 3 to 7 years in four patients after transhumeral amputation. The implant allowed for bidirectional communication between a prosthetic hand and electrodes implanted in the nerves and muscles of the upper arm and was anchored to the humerus through osseointegration, the process in which bone cells attach to an artificial surface without formation of fibrous tissue. Use of the device did not require formal training and depended on the intuitive intent of the user to activate movement and sensory feedback from the prosthesis. Daily use resulted in increasing sensory acuity and effectiveness in work and other activities of daily life. (Funded by the Promobilia Foundation and others.)
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5.
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6.
  • Tamminen, T., et al. (författare)
  • Mobile and flexible processing of biomass – EU project Mobile Flip
  • 2015
  • Ingår i: VTT Technology. - 2242-1211. ; , s. 28-41
  • Konferensbidrag (refereegranskat)abstract
    • EU project MOBILE FLIP in the SPIRE program aims at developing and demonstrating mobile processes for the treatment of underexploited agro- and forest based biomass resources into products and intermediates. The processes are evaluated in terms of raw material flexibility, as the biomass resources are typically scattered and seasonal. Process concepts have been designed around the key technologies pelletizing, torrefaction, slow pyrolysis, hydrothermal pretreatment and carbonisation. The products vary depending on the process concept, being typically fuels as such or for co-combustion (pellets, torrefied pellets, biocoals), biochars for soil remediation, biodegradable pesticides for agricultural or forestry use or chemicals for wood panel industry and sugars and hydrolysable cellulose as intermediate for the sugar platform. The concept evaluations are supported both by research and industrial (SME and large industries) partners in the whole value chains. Dissemination, communication and exploitation activities are an integral part of the project. Life-cycle analysis and a wide sustainability evaluation (economic, environmental and social assessment) are carried out for the process concepts in order to clarify their potential for flexible raw material valorisation. The partners are represented by the coauthors in this presentation: four SMEs, two large companies, six research organizations. The project duration is four years and total budget approximately EUR 10 million.
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7.
  • Zackrisson, Martin, et al. (författare)
  • Scan-o-matic: High-Resolution Microbial Phenomics at a Massive Scale
  • 2016
  • Ingår i: G3: Genes, Genomes, Genetics. - : Oxford University Press (OUP). - 2160-1836. ; 6:9, s. 3003-3014
  • Tidskriftsartikel (refereegranskat)abstract
    • The capacity to map traits over large cohorts of individuals—phenomics—lags far behind the explosive development in genomics. For microbes, the estimation of growth is the key phenotype because of its link to fitness. We introduce an automated microbial phenomics framework that delivers accurate, precise, and highly resolved growth phenotypes at an unprecedented scale. Advancements were achieved through the introduction of transmissive scanning hardware and software technology, frequent acquisition of exact colony population size measurements, extraction of population growth rates from growth curves, and removal of spatial bias by reference-surface normalization. Our prototype arrangement automatically records and analyzes close to 100,000 growth curves in parallel. We demonstrate the power of the approach by extending and nuancing the known salt-defense biology in baker’s yeast. The introduced framework represents a major advance in microbial phenomics by providing high-quality data for extensive cohorts of individuals and generating well-populated and standardized phenomics databases
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8.
  • Säljö, Karin, 1981, et al. (författare)
  • Successful engraftment, vascularization, and In vivo survival of 3D-bioprinted human lipoaspirate-derived adipose tissue
  • 2020
  • Ingår i: Bioprinting. - : Elsevier BV. - 2405-8866. ; 17
  • Tidskriftsartikel (refereegranskat)abstract
    • Autologous fat grafting is commonly used for correction of soft-tissue deformities, despite a high rate of graft resorption and nutrition-supply challenges. Three-dimensional (3D)-bioprinting techniques enable tailor-made architecture of grafts and promote vascularization. In recent years, the importance of adipose tissue-derived stromal/stem cells (ASCs) for graft survival has become evident. This study investigated the printability of mechanically processed lipoaspirate containing ASCs, as well as in vivo survival and neovascularisation of the 3D-bioprinted grafts. Human lipoaspirate-derived adipose tissue was 3D bioprinted in alginate/nanocellulose bioink, implanted into nude mice, and harvested at days 3, 7, and 30, respectively. The processed lipoaspirate showed high viability and good printability when combined with alginate/nanocellulose, and the 3D-bioprinted grafts contained intact vascular structures and a high density of mature adipocytes before and after engraftment. After 30 days in vivo, novel blood vessels were present on the graft surface, showing signs of angiogenesis into the graft, as well as vascularization in the centre of the tissue. Moreover, histologic and immunohistochemical characterisation confirmed the presence of potential ASCs during the first week in vivo. These results demonstrated that human lipoaspirate-derived adipose tissue showed high printability, survived 3D bioprinting and engraftment in vivo, and displayed macroscopic and microscopic evidence of vascularization.
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9.
  • Apelgren, Peter, et al. (författare)
  • Skin Grafting on 3D Bioprinted Cartilage Constructs In Vivo
  • 2018
  • Ingår i: Plastic and Reconstructive Surgery - Global Open. - 2169-7574. ; 6:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Three-dimensional (3D) bioprinting of cartilage is a promising new technique. To produce, for example, an auricle with good shape, the printed cartilage needs to be covered with skin that can grow on the surface of the construct. Our primary question was to analyze if an integrated 3D bioprinted cartilage structure is a tissue that can serve as a bed for a full-thickness skin graft. Methods: 3D bioprinted constructs (10x10x1.2mm) were printed using nanofibrillated cellulose/alginate bioink mixed with mesenchymal stem cells and adult chondrocytes and implanted subcutaneously in 21 nude mice. Results: After 45 days, a full-thickness skin allograft was transplanted onto the constructs and the grafted construct again enclosed subcutaneously. Group 1 was sacrificed on day 60, whereas group 2, instead, had their skin-bearing construct uncovered on day 60 and were sacrificed on day 75 and the explants were analyzed morphologically. The skin transplants integrated well with the 3D bioprinted constructs. A tight connection between the fibrous, vascularized capsule surrounding the 3D bioprinted constructs and the skin graft were observed. The skin grafts survived the uncovering and exposure to the environment. Conclusions: A 3D bioprinted cartilage that has been allowed to integrate in vivo is a sufficient base for a full-thickness skin graft. This finding accentuates the clinical potential of 3D bioprinting for reconstructive purposes.
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10.
  • Lindahl, Anders, 1954, et al. (författare)
  • Cartilage and Bone Regeneration
  • 2014
  • Ingår i: Tissue Engineering: Second Edition. - Amsterdam : Elsevier, Inc.. ; , s. 529-582
  • Bokkapitel (refereegranskat)abstract
    • This chapter deals with the tissue engineering aspects of one of the mesenchymal tissues-cartilage. It includes a brief description of the different cartilage types and their embryonal origin. Tissue structures including chondrocyte and extracellular matrix components are described in detail. The disease aspect of hyaline cartilage with emphasis on cartilage injuries and the tissue engineering approach to cartilage regeneration with the autologous chondrocyte implantation technique is described in depth. The future aspects of cartilage regeneration techniques with potential cell types other than autologous chondrocytes as well as new promising scaffold techniques are described. © 2015 Elsevier Inc. All rights reserved.
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11.
  • Chen, DeJiu, Associate Professor, et al. (författare)
  • Analyzing Dynamic Operational Conditions of Limb Prosthetic Sockets with a Mechatronics-Twin Framework
  • 2022
  • Ingår i: Applied Sciences. - : MDPI AG. - 2076-3417. ; 12:3, s. 986-986
  • Tidskriftsartikel (refereegranskat)abstract
    • Lower limb prostheses offer a solution to restore the ambulation and self-esteem of amputees. One key component is the prosthetic socket that serves as the interface between prosthetic device and amputee stump and thereby has a wide range of impacts on efficient fitting, appropriate load transmission, operational stability, and control. For the design and optimization of a prosthetic socket, an understanding of the actual intra-socket operational conditions becomes therefore necessary. This is however a difficult task due to the inherent complexity and restricted observability of socket operation. In this study, an innovative mechatronics-twin framework that integrates advanced biomechanical models and simulations with physical prototyping and dynamic operation testing for effective exploration of operational behaviors of prosthetic sockets with amputees is proposed. Within this framework, a specific Stewart manipulator is developed to enable dynamic operation testing, in particular for a well-managed generation of dynamic intra-socket loads and behaviors that are otherwise difficult to observe or realize with the real amputees. A combination of deep learning and Bayesian Inference algorithms is then employed for analyzing the intra-socket load conditions and revealing possible anomalous. 
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12.
  • Apelgren, Peter, et al. (författare)
  • In Vivo Human Cartilage Formation in Three-Dimensional Bioprinted Constructs with a Novel Bacterial Nanocellulose Bioink
  • 2019
  • Ingår i: Acs Biomaterials Science & Engineering. - : American Chemical Society (ACS). - 2373-9878. ; 5:5, s. 2482-2490
  • Tidskriftsartikel (refereegranskat)abstract
    • Bacterial nanocellulose (BNC) is a 3D network of nanofibrils exhibiting excellent biocompatibility. Here, we present the aqueous counter collision (ACC) method of BNC disassembly to create bioink with suitable properties for cartilage-specific 3D-bioprinting. BNC was disentangled by ACC, and fibril characteristics were analyzed. Bioink printing fidelity and shear-thinning properties were evaluated. Cell-laden bioprinted grid constructs (5 X 5 X 1 mm(3)) containing human nasal chondrocytes (10 M mL(-1)) were implanted in nude mice and explanted after 30 and 60 days. Both ACC and hydrolysis resulted in significantly reduced fiber lengths, with ACC resulting in longer fibrils and fewer negative charges relative to hydrolysis. Moreover, ACC-BNC bioink showed outstanding printability, postprinting mechanical stability, and structural integrity. In vivo, cell-laden structures were rapidly integrated, maintained structural integrity, and showed chondrocyte proliferation, with 32.8 +/- 13.8 cells per mm(2) observed after 30 days and 85.6 +/- 30.0 cells per mm(2) at day 60 (p = 0.002). Furthermore, a full-thickness skin graft was attached and integrated completely on top of the 3D-bioprinted construct. The novel ACC disentanglement technique makes BNC biomaterial highly suitable for 3D-bioprinting and clinical translation, suggesting cell-laden 3D-bioprinted ACC-BNC as a promising solution for cartilage repair.
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13.
  • Sämfors, Sanna, 1987, et al. (författare)
  • Biofabrication of bacterial nanocellulose scaffolds with complex vascular structure
  • 2019
  • Ingår i: Biofabrication. - : IOP Publishing. - 1758-5082 .- 1758-5090. ; 11:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Bacterial nanocellulose (BNC) has proven to be an effective hydrogel-like material for different tissue engineering applications due to its biocompatibility and good mechanical properties. However, as for all biomaterials, in vitro biosynthesis of large tissue constructs remains challenging due to insufficient oxygen and nutrient transport in engineered scaffold-cell matrices. In this study we designed, biofabricated and evaluated bacterial nanocellulose scaffolds with a complex vascular mimetic lumen structure. As a first step a method for creating straight channeled structures within a bacterial nanocellulose scaffold was developed and evaluated by culturing of Human Umbilical Vein Endothelial Cells (HUVECs). In a second step, more complex structures within the scaffolds were produced utilizing a 3D printer. A print mimicking a vascular tree acted as a sacrificial template to produce a network within the nanoporous bacterial nanocellulose scaffolds that could be lined with endothelial cells. In a last step, a method to produce large constructs with interconnected macro porosity and vascular like lumen structure was developed. In this process patient data from x-ray computed tomography scans was used to create a mold for casting a full-sized kidney construct. By showing that the 3D printing technology can be combined with BNC biosynthesis we hope to widen the opportunities of 3D printing, while also enabling the production of BNC scaffolds constructs with tailored vascular architectures and properties.
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14.
  • Singh, Shikha, et al. (författare)
  • Orientation of Polylactic Acid–Chitin Nanocomposite Films via Combined Calendering and Uniaxial Drawing: Effect on Structure, Mechanical, and Thermal Properties
  • 2021
  • Ingår i: Nanomaterials. - : MDPI. - 2079-4991. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • The orientation of polymer composites is one way to increase the mechanical properties of the material in a desired direction. In this study, the aim was to orient chitin nanocrystal (ChNC)-reinforced poly(lactic acid) (PLA) nanocomposites by combining two techniques: calendering and solid-state drawing. The effect of orientation on thermal properties, crystallinity, degree of orientation, mechanical properties and microstructure was studied. The orientation affected the thermal and structural behavior of the nanocomposites. The degree of crystallinity increased from 8% for the isotropic compression-molded films to 53% for the nanocomposites drawn with the highest draw ratio. The wide-angle X-ray scattering results confirmed an orientation factor of 0.9 for the solid-state drawn nanocomposites. The mechanical properties of the oriented nanocomposite films were significantly improved by the orientation, and the pre-orientation achieved by film calendering showed very positive effects on solid-state drawn nanocomposites: The highest mechanical properties were achieved for pre-oriented nanocomposites. The stiffness increased from 2.3 to 4 GPa, the strength from 37 to 170 MPa, the elongation at break from 3 to 75%, and the work of fracture from 1 to 96 MJ/m3. This study demonstrates that the pre-orientation has positive effect on the orientation of the nanocomposites structure and that it is an extremely efficient means to produce films with high strength and toughness.
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15.
  • Amoroso, Matteo, 1984, et al. (författare)
  • Functional and morphological studies of in vivo vascularization of 3D-bioprinted human fat grafts
  • 2021
  • Ingår i: Bioprinting. - : Elsevier BV. - 2405-8866. ; 23
  • Tidskriftsartikel (refereegranskat)abstract
    • Three-dimensional (3D) bioprinting offers the ability to design and biofabricate 3D structures based on autologous fat; however, the lack of vascularization in larger 3D-bioprinted constructs represents a limiting factor that hampers translation of this technology from bench to bedside. 3D bioprinting using microfractured fat mixed with nanocellulose–alginate hydrogel can promote vascularization through connections of fragments of vessels included in the fat. In this study, we determined the perfusion and diffusion characteristics of 3D-bioprinted fat constructs using magnetic resonance imaging (MRI) and assessed correlations between perfusion and angiogenesis within the printed constructs. Microfractured human fat from liposuction was printed with tunicate nanocellulose–alginate hydrogel, followed by transplantation of the constructs (10 × 10 × 3 mm) into nude mice that underwent longitudinal MRI for up to 99 days. Confirmation of vascularization was undertaken using immunohistochemical and histologic analyses. Before implantation, the constructs contained abundant fat tissue and fragments of human blood vessels (CD31+ and Ku80+), with subsequent in vivo MRI analysis following transplantation indicating low perfusion and suggesting their continued survival mainly by diffusion. Additionally, we observed a high diffusion coefficient (~2 × 10−3 mm2/s) that was preserved throughout the observation period. Following explantation, evaluation revealed that the constructs displayed preserved histology along with a mixture of human (Ku80+) and murine (Ku80−) erythrocyte-containing vessels. These results demonstrated successful interconnection of blood-vessel fragments from microfractured human fat via angiogenesis to form a vascular network with the host circulation, thereby confirming vascularization of the 3D-bioprinted fat constructs.
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16.
  • Enejder, Annika, 1969, et al. (författare)
  • SHG Imaging for Tissue Engineering Applications
  • 2016
  • Ingår i: Second Harmonic Generation Imaging. - : CRC Press. - 9781439849156 - 9781439849149 ; , s. 409-426
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Treatment of lost tissue oen relies on transplantations, either of donor or of autologous tissue. Both alternatives have limitations; there is for example a limited supply of donor transplants, which also require immunosuppression therapy with possible side eects. Transplanted autologous tissue may lack some of the functions of the original tissue and the procedure may also introduce complications at the donor site. In some cases, articial substitutes manufactured from nonbiological materials can be used, for example, synthetic polymer blood vessels or joint replacement prostheses. However, these replacements have drawbacks such as risk for infections, limited material durability, and lack of mechanisms for repair, growth, and remodeling. For these reasons, development of advanced articial tissue constructs with adaptive capabilities is desirable.
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17.
  • Depauw, V., et al. (författare)
  • Sunlight-thin nanophotonic monocrystalline silicon solar cells
  • 2017
  • Ingår i: Nano Futures. - : IOP Publishing. - 2399-1984. ; 1:2
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Introducing nanophotonics into photovoltaics sets the path for scaling down the surface texture of crystalline-silicon solar cells from the micro-to the nanoscale, allowing to further boost the photon absorption while reducing silicon material loss. However, keeping excellent electrical performance has proven to be very challenging, as the absorber is damaged by the nanotexturing and the sensitivity to the surface recombination is dramatically increased. Here we realize a light-wavelength-scale nanotextured monocrystalline silicon cell with the confirmed efficiency of 8.6% and an effective thickness of only 830 nm. For this we adopt a self-assembled large-area and industry-compatible amorphous ordered nanopatterning, combined with an advanced surface passivation, earning strongly enhanced solar light absorption while retaining efficient electron collection. This prompts the development of highly efficient flexible and semitransparent photovoltaics, based on the industrially mature monocrystalline silicon technology.
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18.
  • Iredahl, Fredrik, 1988- (författare)
  • Assessment of microvascular and metabolic responses in the skin
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The general aim of this project was to develop experimental in vivo models that allow for minimally invasive investigations of responses in the skin to microvascular and metabolic provocations. The cutaneous microvasculature has emerged as a valuable model and been proposed to mirror the microcirculation in other organs. Dysfunction in the cutaneous microcirculation has thus been linked to systemic diseases such as hypertension and diabetes mellitus. Models for investigating skin responses could facilitate the understanding of pathophysiological mechanisms as well as effects of drugs.In the first study, three optical measurement techniques (laser Doppler flowmetry (LDF), laser speckle contrast imaging (LSCI) and tissue viability imaging (TiVi)) were compared against each other and showed differences in their ability to detect microvascular responses to provocations in the skin. TiVi was found more sensitive for measurement of noradrenaline-induced vasoconstriction, while LSCI was more sensitive for measurement of vascular occlusion. In the second study, microvascular responses in the skin to iontophoresis of vasoactive drugs were found to depend on the drug delivery protocol. Perfusion half-life was defined and used to describe the decay in the microvascular response to a drug after iontophoresis. In the third study, the role of nitric oxide (NO) was assessed during iontophoresis of insulin. The results showed a NO-dependent vasodilation in the skin by insulin. In the fourth study the vasoactive and metabolic effects of insulin were studied after both local and endogenous administration. Local delivery of insulin increased skin blood flow, paralleled by increased skin concentrations of interstitial pyruvate and lactate, although no change in glucose concentration was observed. An oral glucose load resulted in an increased insulin concentration in the skin paralleled by an increase in blood flow, as measured using the microdialysis urea clearance technique, although no changes in perfusion was measured by LSCI.The thesis concludes that when studying skin microvascular responses, the choice of measurement technique and the drug delivery protocol has an impact on the measurement results, and should therefore be carefully considered. The thesis also concludes that insulin has metabolic and vasodilatory effects in the skin both when administered locally and as an endogenous response to an oral glucose load. The vasodilatory effect of insulin in the skin is mediated by nitric oxide.
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19.
  • Abid, Suleman, et al. (författare)
  • Synthesis and characterization of glycol chitosan coated selenium nanoparticles acts synergistically to alleviate oxidative stress and increase ginsenoside content in Panax ginseng
  • 2021
  • Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 267
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of the present study is synthesis of glycol chitosan coated selenium nanoparticles (GC-Se NPs) and evaluation of oxidative stress and ginsenoside accumulation in P. ginseng C. A. Meyer. We synthesized (Se NPs and GC-Se NPs) and characterized using various spectroscopic analyses. The highest concentration (20 mg L−1) of GC-Se NPs induced moderate ROS (O2[rad]− and H2O2) accumulation and upregulation of PgSOD and PgCAT showing good biocompatibility and less toxicity at the highest concentration. Furthermore, ginsenoside biosynthetic pathway genes (PgHMGR, PgSS, PgSE, PgDDS) also showed significant upregulation upon 20 mg L−1 GC-Se NPs treatment. At 20 mg L−1 GC-Se NPs treatment, ginsenoside accumulated upto 217.47 mg/mL and 169.86 mg/mL mainly due to the increased proportion of Rb1 and Re ginsenosides. Altogether, our results suggested that ecofriendly conjugation of GC with Se NPs could be used as a bio fortifier to enhance the ginsenoside profile and to increase the quality of ginseng roots.
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20.
  • Atefyekta, Saba, 1987, et al. (författare)
  • Antibiofilm elastin-like polypeptide coatings: functionality, stability, and selectivity
  • 2019
  • Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 83, s. 245-256
  • Tidskriftsartikel (refereegranskat)abstract
    • Antimicrobial peptides (AMPS) are currently receiving interest as an alternative to conventional antibiotics to treat biomaterial-associated infection. However, the inherent instability of such peptides often limits their efficacy in intended clinical applications. Covalent immobilization of AMPs to surfaces is one strategy to increase the long-term stability and minimize the toxicity. In this work, an antimicrobial peptide, RRPRPRPRPWWWW-NH2 (RRP9W4N), was used to modify elastin-like polypeptide (ELP) surface coatings containing cell-adhesive peptide domains (RGD) using covalent chemistry. The AMP retained its antibacterial activity against Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa when covalently bonded to ELP surfaces. Simultaneously, the AMP functionalization had insignificant effect on the viability, function, and differentiation of human osteosarcoma MG63 cells and human mesenchymal stem cells (hMSCs). Furthermore, stability of the immobilized AMP in human blood serum was investigated, and the results suggested that the AMP preserved its antibacterial activity up to 24 h. Combined, the results show that covalently attached AMPs onto RGD-containing ELP are an excellent candidate as an antimicrobial coating for medical devices.
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21.
  • Nilsson, Avlant, 1985, et al. (författare)
  • Metabolite Depletion Affects Flux Profiling of Cell Lines
  • 2018
  • Ingår i: Trends in Biochemical Sciences. - : Elsevier BV. - 1362-4326 .- 0968-0004. ; 43:6, s. 395-397
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Quantifying the rate of consumption and release of metabolites (i.e., flux profiling) has become integral to the study of cancer. The fluxes as well as the growth of the cells may be affected by metabolite depletion during cultivation.
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22.
  • Mousavi, Monirehalsadat, et al. (författare)
  • Photodynamic therapy dosimetry using multiexcitation multiemission wavelength : toward real-time prediction of treatment outcome
  • 2020
  • Ingår i: Journal of Biomedical Optics. - 1560-2281. ; 25:6, s. 1-14
  • Tidskriftsartikel (refereegranskat)abstract
    • Evaluating the optical properties of biological tissues is needed to achieve accurate dosimetry during photodynamic therapy (PDT). Currently, accurate assessment of the photosensitizer (PS) concentration by fluorescence measurements during PDT is typically hindered by the lack of information about tissue optical properties. In the present work, a hand-held fiber-optic probe instrument monitoring fluorescence and reflectance is used for assessing blood volume, reduced scattering coefficient, and PS concentration facilitating accurate dosimetry for PDT. System validation was carried out on tissue phantoms using nonlinear least squares support machine regression analysis. It showed a high correlation coefficient (>0.99) in the prediction of the PS concentration upon a large variety of phantom optical properties. In vivo measurements were conducted in a PDT chlorine e6 dose escalating trial involving 36 male Swiss mice with Ehrlich solid tumors in which fluences of 5, 15, and 40 J cm - 2 were delivered at two fluence rates (100 and 40 mW cm - 2). Remarkably, quantitative measurement of fluorophore concentration was achieved in the in vivo experiment. Diffuse reflectance spectroscopy (DRS) system was also used to independently measure the physiological properties of the target tissues for result comparisons. Then, blood volume and scattering coefficient measured by the fiber-optic probe system were compared with the corresponding result measured by DRS and showed agreement. Additionally, tumor hemoglobin oxygen saturation was measured using the DRS system. Overall, the system is capable of assessing the implicit photodynamic dose to predict the PDT outcome.
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23.
  • Cruz, Javier, 1990- (författare)
  • Microfluidics for High-Pressure Inertial Focusing : Focusing, Separation and Concentration of Micro and Sub-micron Particles
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The birth of microsystems set the ground for technologies never imagined before, for it is not only the small size what characterizes the miniaturized systems, but unique phenomena arise in the micro scale. This thesis relates to one such unique phenomenon, inertial focusing, a phenomenon that occurs in microfluidic systems if very special conditions are met and that allows for fine manipulation of particles in fluid samples. This ability is key in a bigger picture: the analysis of complex fluids, where rare particles of interest may be present in very few numbers amongst a myriad of others, making the task difficult – if not impossible. A system exploiting inertial focusing allows, for instance, to focus, separate, isolate and concentrate such rare particles of interest, and even to transfer them to another fluid, thereby enabling/facilitating their detection and analysis. Examples of rare particles of interest in complex fluids are circulating tumor cells in blood, that give away the presence of cancer, extracellular vesicles also in blood, that contain biomarkers with physiological and pathological information about the patient, or bacteria in natural water, where the species present and their numbers are to be monitored for safety reasons and/or biological studies. This thesis covers the state of art physical principles behind the phenomenon and extends the understanding both in theory and applications. Specifically, the technology is extended to allow for manipulation of sub-micron particles, a range of interest as it comprises bacteria, viruses and organelles of eukaryotic cells. This was possible by an analysis of the balance of forces in play and by the integration of inertial focusing in high-pressure systems (up to 200 bar). In a second block, a very special line of inertial focusing is introduced and developed; inertial focusing in High Aspect Ratio Curved (HARC) microfluidics. These systems, engineered to rearrange the force field responsible for the particle manipulation, not only achieve excellent performances for focusing and concentration of particles, but also extreme resolution in their separation (mathematically unlimited; demonstrated experimentally for differences in size down to 80 nm). Perhaps more important than the performance, the systems are stable, intuitive and simpler to design, attributes that we hope will make the technology and its outstanding benefits more accessible to the community. With its remarkable performance, it would not come as a surprise if, in the near future, inertial focusing makes a strong impact on how analyses are performed nowadays and opens up for possibilities beyond the current state of the art.
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24.
  • Atefyekta, Saba, 1987 (författare)
  • Antibacterial Surfaces for Biomedical Applications
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Medical devices such as orthopedic implants are intended to serve for improved quality of life. However, clinical success cannot be taken for granted and the most common reason for failure is due to biomaterials associated infection (BAI). An implantation surgical site is a susceptible environment for bacterial colonization, which in combination with compromised immune system, results in that bacteria can develop biofilms on the implant surface or in adjacent tissue. Once such a biofilm has established, it may lead to an infection that cannot be eradicated by means of traditional antibiotics, often resulting in revision surgery. Wounds after post implantation surgery is another risk for bacterial colonization into underlying tissue and increases further the susceptibility to infection. These and other bacteria related complications are today becoming more serious due to the rapid increase of antibiotic resistance worldwide. This has resulted in that many available antibiotics are losing their potency against bacteria and consequently, treating an infection with antibiotics is not working as effectively as in the past. The objective of this thesis was to find new solutions to address the complications associated with bacterial colonization through applying preventive measures by designing antibacterial surfaces for inhibition of early biomaterials associated and wound infection. For this purpose, two types of antibacterial surfaces were designed and evaluated. In the first type, a local drug-delivery system based on mesoporous Titania thin films were developed. These films were to serve as implant coatings where antibiotics are released locally at the implantation site to prevent biofilm formation and subsequent tissue colonization. In the second approach, antibacterial surfaces were developed through covalent immobilization of a cationic antimicrobial peptide (AMP), thus creating surfaces that kill bacteria upon contact. The overall results in this thesis, which are presented as four papers, suggest that the developed antibacterial surfaces are promising to use in future biomedical applications.
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25.
  • Jankovskaja, Skaidre, et al. (författare)
  • Visualisation of H2O2 penetration through skin indicates importance to develop pathway-specific epidermal sensing
  • 2020
  • Ingår i: Microchimica Acta. - : Springer. - 0026-3672 .- 1436-5073. ; 187:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated amounts of reactive oxygen species (ROS) including hydrogen peroxide (H2O2) are observed in the epidermis in different skin disorders. Thus, epidermal sensing of H2O2 should be useful to monitor the progression of skin pathologies. We have evaluated epidermal sensing of H2O2 in vitro, by visualising H2O2 permeation through the skin. Skin membranes were mounted in Franz cells, and a suspension of Prussian white microparticles was deposited on the stratum corneum face of the skin. Upon H2O2 permeation, Prussian white was oxidised to Prussian blue, resulting in a pattern of blue dots. Comparison of skin surface images with the dot patterns revealed that about 74% of the blue dots were associated with hair shafts. The degree of the Prussian white to Prussian blue conversion strongly correlated with the reciprocal resistance of the skin membranes. Together, the results demonstrate that hair follicles are the major pathways of H2O2 transdermal penetration. The study recommends that the development of H2O2 monitoring on skin should aim for pathway-specific epidermal sensing, allowing micrometre resolution to detect and quantify this ROS biomarker at hair follicles. Graphical abstract
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26.
  • Jonsson, L., et al. (författare)
  • High expression of RNA-binding motif protein 3 in esophageal and gastric adenocarcinoma correlates with intestinal metaplasia-associated tumours and independently predicts a reduced risk of recurrence and death
  • 2014
  • Ingår i: Biomarker Research. - : BioMed Central Ltd.. - 2050-7771. ; 2:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: High nuclear expression of the RNA-binding motif protein 3 (RBM3) has previously been found to correlate with favourable clinicopathological characteristics and a prolonged survival in several cancer forms. Here, we examined the clinicopathological correlates and prognostic significance of RBM3 expression in tumours from a consecutive cohort of upper gastrointestinal adenocarcinoma.Material and methods: Immunohistochemical RBM3 expression was analysed in tissue microarrays with primary radiotherapy- and chemotherapy-naive adenocarcinoma of the esophagus, gastroesophageal junction and stomach (n = 173). In addition paired samples of normal squamous epithelium (n = 53), gastric mucosa (n = 117), Barrett's esophagus/gastric intestinal metaplasia (n = 61) and lymph node metastases (n = 71) were analysed. Kaplan-Meier analysis and Cox proportional hazards modelling was applied to assess the impact of RBM3 expression on overall survival (OS) and recurrence-free survival (RFS).Results: RBM3 expression was similar in primary tumours and lymph node metastases, but significantly higher in primary tumours and metastases arising in a background of intestinal metaplasia compared with cases without intestinal metaplasia (p < 0.001). RBM3 expression was significantly reduced in more advanced tumour stages (p = 0.006). Low RBM3 expression was significantly associated with a shorter OS in cases with radically resected (R0) tumours (HR 2.19, 95% CI 1.33-3.61, p = 0.002) and RFS in curatively treated patients with R0 resection/distant metastasis-free disease (HR = 3.21, 95% CI 1.64-6.30, p = 0.001). These associations remained significant in adjusted analysis (HR = 1.95, 95% CI 1.17-3.25, p = 0.010 for OS and HR = 3.02, 95% CI 1.45-6.29, p = 0.003 for RFS).Conclusion: High expression of RBM3 may signify a subset of upper gastrointestinal cancers arising in a background of intestinal metaplasia and independently predicts a reduced risk of recurrence and death in patients with these cancer forms. These findings are of potential clinical utility and merit further validation. 
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27.
  • Roos, Håkan, 1967, et al. (författare)
  • Displacement Forces in Stent Grafts: Influence of Diameter Variation and Curvature Asymmetry
  • 2016
  • Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 52:2, s. 150-156
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Long-term durability after endovascular aortic repair is influenced by stent graft migration causing types I and III endoleaks. Flow induced displacement forces have been shown to have the potential to cause migration. In this study, the influence of the distal diameter of iliac limb stent grafts and the shape of graft curvature on flow induced displacement forces, were investigated. Methods: In an experimental pulsatile flow model mimicking aortic conditions in vivo, flow induced displacement forces at the proximal and distal ends of iliac limb stent grafts were studied at different angles (0-90 degrees) and perfusion pressures (145/80, 170/90, 195/100 mmHg). Bell-bottomed, tapered, and non-tapered stent grafts and also asymmetric stent graft curvatures at 90 bend were studied. Measurements of graft movement were performed at all studied angulations and graft shapes. Results: For all stent graft diameters, flow induced displacement forces increased with higher pressure and increased stent graft angulation. Forces in the bell-bottom graft were considerably higher than in tapered and non-tapered grafts, with a markedly elevated peak force at the distal end (proximal end, 2.3 +/- 0.06 N and distal end, 6.9 +/- 0.05 N compared with 1.7 +/- 0.08 N and 1.6 +/- 0.08 N in non-tapered grafts; p <.001 both). Peak forces in tapered and non-tapered grafts were not significantly different between the proximal and distal end. In asymmetric stent graft curvatures, a significant increase in displacement forces was observed in the attachment zone that was closest to the stent graft bend. Graft movement increased with greater displacement forces. Conclusion: Flow induced displacement forces in iliac limb stent grafts are significant and are influenced by distal stent graft diameter and the shape of the graft curvature. The displacement forces are particularly high at the large distal end of bell-bottom grafts. Wide iliac arteries treated with bell-bottom stent grafts may require more vigilant surveillance and improved stent graft fixation.
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28.
  • Ghorbanpour, F., et al. (författare)
  • Marked point process analysis of epidermal nerve fibres
  • 2021
  • Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 283:1, s. 41-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Epidermal nerve fibre (ENF) density and summed length of ENFs per epidermal surface area are reduced, and ENFs may appear more clustered within the epidermis in subjects suffering from diabetic neuropathy compared to healthy subjects. Therefore, it is important to understand the spatial behaviour of ENFs in healthy and neuropathy subjects. By using confocal microscopy data , we study the spatial structure of epidermal nerves by regarding the nerve tree locations as realizations of marked point processes . The termination points of the fibres of a nerve tree are used to define a reactive territory which is taken as a mark for the nerve tree location. We study the differences in the spatial pattern of ENFs between healthy subjects and subjects suffering from mild diabetic neuropathy by using Ripley's K function and the mark correlation function. In addition, we propose a marked sequential point process model for the nerve tree locations. Data are replicated point patterns, where we have several patterns from each subject and from each group.
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29.
  • Wright, Leah, et al. (författare)
  • A membrane-free microfluidic approach to mucus permeation for efficient differentiation of mucoadhesive and mucopermeating nanoparticulate systems
  • 2023
  • Ingår i: Drug Delivery and Translational Research. - : Springer Science and Business Media LLC. - 2190-393X .- 2190-3948. ; 13:4, s. 1088-1101
  • Tidskriftsartikel (refereegranskat)abstract
    • The gastrointestinal mucus barrier is a widely overlooked yet essential component of the intestinal epithelium, responsible for the body’s protection against harmful pathogens and particulates. This, coupled with the increasing utilisation of biological molecules as therapeutics (e.g. monoclonal antibodies, RNA vaccines and synthetic proteins) and nanoparticle formulations for drug delivery, necessitates that we consider the additional absorption barrier that the mucus layer may pose. It is imperative that in vitro permeability methods can accurately model this barrier in addition to standardised cellular testing. In this study, a mucus-on-a-chip (MOAC) microfluidic device was engineered and developed to quantify the permeation kinetics of nanoparticles through a biorelevant synthetic mucus layer. Three equivalently sized nanoparticle systems, formulated from chitosan (CSNP), mesoporous silica (MSNP) and poly (lactic-co-glycolic) acid (PLGA-NP) were prepared to encompass various surface chemistries and nanostructures and were assessed for their mucopermeation within the MOAC. Utilising this device, the mucoadhesive behaviour of chitosan nanoparticles was clearly visualised, a phenomenon not often observed via standard permeation models. In contrast, MSNP and PLGA-NP displayed mucopermeation, with significant differences in permeation pattern due to specific mucus-nanoparticle binding. Further optimisation of the MOAC to include a more biorelevant mucus mimic resulted in 5.5-fold hindered PLGA-NP permeation compared to a mucin solution. Furthermore, tracking of PLGA-NP at a single nanoparticle resolution revealed rank-order correlations between particle diffusivity and MOAC permeation. This device, including utilisation of biosimilar mucus, provides a unique ability to quantify both mucoadhesion and mucopenetration of nano-formulations and elucidate mucus binding interactions on a microscopic scale. Graphical abstract : [Figure not available: see fulltext.]
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30.
  • Konstantionu, Konstantinos, et al. (författare)
  • Spatial modeling of epidermal nerve fiber patterns
  • 2021
  • Ingår i: Statistics in Medicine. - : Wiley. - 0277-6715 .- 1097-0258. ; 40:29, s. 6479-6500
  • Tidskriftsartikel (refereegranskat)abstract
    • Peripheral neuropathy is a condition associated with poor nerve functionality. Epidermal nerve fiber (ENF) counts per epidermal surface are dramatically reduced and the two-dimensional (2D) spatial structure of ENFs tends to become more clustered as neuropathy progresses. Therefore, studying the spatial structure of ENFs is essential to fully understand the mechanisms that guide those morphological changes. In this article, we compare ENF patterns of healthy controls and subjects suffering from mild diabetic neuropathy by using suction skin blister specimens obtained from the right foot. Previous analysis of these data has focused on the analysis and modeling of the spatial ENF patterns consisting of the points where the nerves enter the epidermis, base points, and the points where the nerve fibers terminate, end points, projected on a 2D plane, regarding the patterns as realizations of spatial point processes. Here, we include the first branching points, the points where the nerve trees branch for the first time, and model the three-dimensional (3D) patterns consisting of these three types of points. To analyze the patterns, spatial summary statistics are used and a new epidermal active territory that measures the volume in the epidermis that is covered by the individual nerve fibers is constructed. We developed a model for both the 2D and the 3D patterns including the branching points. Also, possible competitive behavior between individual nerves is examined. Our results indicate that changes in the ENFs spatial structure can more easily be detected in the later parts of the ENFs.
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31.
  • Ghaderi, Mohammadamir, 1986, et al. (författare)
  • Thermally regenerable optical transparent MEMS windows for exhaust gas analysis
  • 2020
  • Ingår i: Optics InfoBase Conference Papers.
  • Konferensbidrag (refereegranskat)abstract
    • Exhaust gas measurement in the harsh environment of the tailpipe by optical techniques is a highly robust technique, provided that optical access is maintained in the presence of soot. The design, fabrication, and testing of membranes in SiC-on-Si with integrated heaters to serve as a regenerable MEMS optical window into the tailpipe are presented. Membranes at slightly elevated temperatures are demonstrated to keep the surface transparent by thermophoresis, while surface regeneration is achieved at pulsed high temperatures, which allows long-term optical measurement in the exhaust.
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32.
  • Lundström, Carl Peter, 1982, et al. (författare)
  • Fiber-optic parametric amplifiers without pump dithering
  • 2013
  • Ingår i: Optics InfoBase Conference Papers. - Washington, D.C. : OSA. - 2162-2701.
  • Konferensbidrag (refereegranskat)abstract
    • We present passively stimulated Brillouin scattering-suppressed highly nonlinear fiber cascades, and use them to implement fiber-optic parametric amplifiers capable of up to 10 dB net parametric gain without pump dithering.
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33.
  • Lundström, Linda, et al. (författare)
  • Off-axis wave front measurements for optical correction in eccentric viewing
  • 2005
  • Ingår i: Journal of Biomedical Optics. - : SPIE-Intl Soc Optical Eng. - 1083-3668 .- 1560-2281. ; 10:3
  • Tidskriftsartikel (refereegranskat)abstract
    • In a previous study we have shown that correction of peripheral refractive errors can improve the remaining vision of subjects with large central visual field loss. Measuring peripheral refractive errors with traditional methods is often difficult due to low visual acuity and large aberrations. Therefore a Hartmann-Shack sensor has been designed to measure peripheral wave front aberrations in subjects using eccentric viewing. The sensor incorporates an eye tracker and analyzing software designed to handle large wave front aberrations and elliptic pupils. To ensure that the measurement axis is aligned with the direction of the subject's preferred retinal location, a special fixation target has been developed. It consists of concentric rings surrounding the aperture of the sensor together with a central fixation mark along the measurement axis. Some initial measurements on subjects using eccentric viewing have been performed successfully. As a first step in improving the peripheral optics of the eye, the wave front has been used to calculate the eccentric refraction. This refraction has been compared to the refraction found with the Power-Refractor instrument. Measuring the off-axis wave front is a fast way to assess the optical errors in the subject's eccentric viewing angle and to better understand the problems of eccentric correction.
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34.
  • Naren, Gaowa, 1990, et al. (författare)
  • Rapid amplitude-modulation of a diarylethene photoswitch: en route to contrast-enhanced fluorescence imaging
  • 2021
  • Ingår i: Chemical Science. - : Royal Society of Chemistry (RSC). - 2041-6539 .- 2041-6520. ; 12:20, s. 7073-7078
  • Tidskriftsartikel (refereegranskat)abstract
    • A water soluble diarylethene (DAE) derivative that displays exceptionally intense fluorescence from the colorless open form has been synthesized and characterized using UV/vis spectroscopy and fluorescence microscopy. We show that the bright emission from the open form can be rapidly switched using amplitude modulated red light, that is, by light at wavelengths longer than those absorbed by the fluorescent species. This is highly appealing in any context where undesired background fluorescence disturbs the measurement, e.g., the autofluorescence commonly observed in fluorescence microscopy. We show that this scheme is conveniently applicable using lock-in detection, and that robust amplitude modulation of the probe fluorescence is indeed possible also in cell studies using fluorescence microscopy.
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35.
  • Dev, Apurba, et al. (författare)
  • Electrokinetic effect for molecular recognition : A label-free approach for real-time biosensing
  • 2016
  • Ingår i: Biosensors & bioelectronics. - : Elsevier. - 0956-5663 .- 1873-4235. ; 82, s. 55-63
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a simple and inexpensive method for label-free detection of biomolecules. The method monitors the changes in streaming current in a fused silica capillary as target biomolecules bind to immobilized receptors on the inner surface of the capillary. To validate the concept, we show detection and time response of different protein-ligand and protein-protein systems: biotin-avidin and biotin-streptavidin, barstar-dibarnase and Z domain-immunoglobulin G (IgG). We show that specific binding of these biomolecules can be reliably monitored using a very simple setup. Using sequential injections of various proteins at a diverse concentration range and as well as diluted human serum we further investigate the capacity of the proposed technique to perform specific target detection from a complex sample. We also investigate the time for the signal to reach equilibrium and its dependence on analyte concentration and demonstrate that the current setup can be used to detect biomolecules at a concentration as low as 100 pM without requiring any advanced device fabrication procedures. Finally, an analytical model based on diffusion theory has been presented to explain the dependence of the saturation time on the analyte concentration and capillary dimensions and how reducing length and inner diameter of the capillary is predicted to give faster detection and in practice also lower limit of detection.
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36.
  • Wallin, Patric, 1985 (författare)
  • Creating cell microenvironments in vitro
  • 2012
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Stem cells have a great potential to bring about advancements in fields like developmental biology, drug discovery, cancer biology and tissue engineering. In order to be able to use stem cells to their full potential, it is important to have control over their behavior. In vivo cellular fate processes are controlled by the microenvironment around them and the many different factors in it. Cells communicate with their surrounding environment and shape it actively via cell-cell, cell-matrix and cell-liquid interactions. These interactions often happen on the cellular and subcellular length scale in defined time dependent sequences. Consequently, it is important to have systems that can provide different molecular cues with a high spatial and temporal resolution, in order to mimic cell microenvironments in vitro and study cells under controlled conditions. This thesis focuses on cell-matrix and cell-liquid interactions and different ways to create cell niches in cell culture systems. The focus is on designing and characterizing microfluidic cell culture platforms and, in particular, systems that are capable of forming molecular gradients. Flow-based and diffusion-based microfluidic gradient generators were combined with substrates coated with biofunctionalized gold nano dots, chemical active molecules, or electrospun microfibers. Thus, it was possible to provide cells with topographical cues and a defined surface chemistry, as well as soluble molecular cues in a gradient manner, simultaneously. COMSOL Multiphysics simulations were used to assist the design process and characterization of the microfluidic systems, and also to study cell receptor binding interactions in great detail. The developed toolbox of COMSOL modeling, a liquid handling system, a variety of microfluidic networks, surface modification techniques and molecular gradients allows the formation of multifactorial microenvironments to now study induction of cellular fate process of different cell types in vitro.
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37.
  • Parkkila, Petteri, 1990, et al. (författare)
  • Protein A/G-based surface plasmon resonance biosensor for regenerable antibody-mediated capture and analysis of nanoparticles
  • 2022
  • Ingår i: Colloids and Surfaces A: Physicochemical and Engineering Aspects. - : Elsevier BV. - 1873-4359 .- 0927-7757. ; 654
  • Tidskriftsartikel (refereegranskat)abstract
    • Characterization of nanoparticles (NPs) and their subpopulations in heterogeneous samples is of utmost importance, for example, during the initial design of targeted NP therapies and the different phases of their production cycle. Biological NPs such as extracellular vesicles (EVs) have shown promise in improving the drug delivery capabilities compared to traditional NP-based therapies, for example, in treating cancer and neurodegenerative diseases. This work presents a general antibody-mediated surface capture and analysis protocol for NPs using a Protein A/G-functionalized surface plasmon resonance biosensor. The use of anti-streptavidin antibodies allows regenerable capture of biotin-containing NPs such as large unilamellar vesicles commonly used as drug delivery vehicles. Furthermore, the use of antibodies directed against glycophorin A and B (CD235a and b) enabled diffusion-limited specific surface capture of red blood cell-derived extracellular vesicles (RBC EVs). RBC EVs showed the efficacy of the biosensor in the determination of size and bulk concentration of NP subpopulations isolated from a complex biological matrix. The mean size of the surface-captured RBC EVs was comparable to the corresponding sizes derived for the entire EV population measured with well-established NP sizing techniques, namely, nanoparticle tracking analysis and dynamic light scattering. Taken together, the Protein A/G-functionalized biosensor provides a generic alternative to the existing NP-capturing sensors based on, for example, covalent antibody attachment, hydrophobic surfaces or biotin-capped self-assembled monolayers.
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38.
  • Zhdanov, Vladimir, 1952 (författare)
  • Pulling-induced rupture of ligand-receptor bonds between a spherically shaped bionanoparticle and the support
  • 2018
  • Ingår i: Physics Letters, Section A: General, Atomic and Solid State Physics. - : Elsevier BV. - 0375-9601. ; 382:15, s. 1052-1057
  • Tidskriftsartikel (refereegranskat)abstract
    • Contacts of biological or biologically-inspired spherically shaped nanoparticles (e.g., virions or lipid nanoparticles used for intracellular RNA delivery) with a lipid membrane of cells are often mediated by multiple relatively weak ligand-receptor bonds. Such contacts can be studied at a supported lipid bilayer. The rupture of bonds can be scrutinized by using force spectroscopy. Bearing a supported lipid bilayer in mind, the author shows analytically that the corresponding dependence of the force on the nanoparticle displacement and the effect of the force on the bond-rupture activation energy are qualitatively different compared to what is predicted by the conventional Bell approximation.
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39.
  • Hyltegren, Kristin, et al. (författare)
  • Adsorption of Fibrinogen on Silica Surfaces-The Effect of Attached Nanoparticles
  • 2020
  • Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 10:3
  • Tidskriftsartikel (refereegranskat)abstract
    • When a biomaterial is inserted into the body, proteins rapidly adsorb onto its surface, creating a conditioning protein film that functions as a link between the implant and adhering cells. Depending on the nano-roughness of the surface, proteins will adsorb in different amounts, with different conformations and orientations, possibly affecting the subsequent attachment of cells to the surface. Thus, modifications of the surface nanotopography of an implant may prevent biomaterial-associated infections. Fibrinogen is of particular importance since it contains adhesion epitopes that are recognized by both eukaryotic and prokaryotic cells, and can therefore influence the adhesion of bacteria. The aim of this study was to model adsorption of fibrinogen to smooth or nanostructured silica surfaces in an attempt to further understand how surface nanotopography may affect the orientation of the adsorbed fibrinogen molecule. We used a coarse-grained model, where the main body of fibrinogen (visible in the crystal structure) was modeled as rigid and the flexible α C-chains (not visible in the crystal structure) were modeled as completely disordered. We found that the elongated fibrinogen molecule preferably adsorbs in such a way that it protrudes further into solution on a nanostructured surface compared to a flat one. This implicates that the orientation on the flat surface increases its bio-availability.
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40.
  • Alerstam, Erik, et al. (författare)
  • Parallel computing with graphics processing units for high-speed Monte Carlo simulation of photon migration.
  • 2008
  • Ingår i: Journal of Biomedical Optics. - : SPIE-Intl Soc Optical Eng. - 1083-3668. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • General-purpose computing on graphics processing units (GPGPU) is shown to dramatically increase the speed of Monte Carlo simulations of photon migration. In a standard simulation of time-resolved photon migration in a semi-infinite geometry, the proposed methodology executed on a low-cost graphics processing unit (GPU) is a factor 1000 faster than simulation performed on a single standard processor. In addition, we address important technical aspects of GPU-based simulations of photon migration. The technique is expected to become a standard method in Monte Carlo simulations of photon migration.
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41.
  • Alerstam, Erik, et al. (författare)
  • White Monte Carlo for time-resolved photon migration.
  • 2008
  • Ingår i: Journal of Biomedical Optics. - : SPIE-Intl Soc Optical Eng. - 1083-3668. ; 13:4
  • Tidskriftsartikel (refereegranskat)abstract
    • A novel scheme for fully scalable White Monte Carlo (WMC) has been developed and is used as a forward solver in the evaluation of experimental time-resolved spectroscopy. Previously reported scaling problems are avoided by storing detection events individually, turning spatial and temporal binning into post-simulation activities. The approach is suitable for modeling of both interstitial and noninvasive settings (i.e., infinite and semi-infinite geometries). Motivated by an interest in in vivo optical properties of human prostate tissue, we utilize WMC to explore the low albedo regime of time-domain photon migration--a regime where the diffusion approximation of radiative transport theory breaks down, leading to the risk of overestimating both reduced scattering (mu(s)') and absorption (mu(a)). Experimental work supports our findings and establishes the advantages of Monte Carlo-based evaluation.
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42.
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43.
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44.
  •  
45.
  • Balian, Alien, et al. (författare)
  • Nucleases as molecular targets for cancer diagnosis
  • 2021
  • Ingår i: Biomarker Research. - : BMC. - 2050-7771. ; 9:1
  • Forskningsöversikt (refereegranskat)abstract
    • Early cancer diagnosis is a crucial element to improved treatment options and survival. Great research efforts have been made in the search for better performing cancer diagnostic biomarkers. However, the quest continues as novel biomarkers with high accuracy for an early diagnosis remain an unmet clinical need. Nucleases, which are enzymes capable of cleaving nucleic acids, have been long considered as potential cancer biomarkers. The implications of nucleases are key for biological functions, their presence in different cellular counterparts and catalytic activity led the enthusiasm towards investigating the role of nucleases as promising cancer biomarkers. However, the most essential feature of these proteins, which is their enzymatic activity, has not been fully exploited. This review discusses nucleases interrogated as cancer biomarkers, providing a glimpse of their physiological roles. Moreover, it highlights the potential of harnessing the enzymatic activity of cancer-associated nucleases as a novel diagnostic biomarker using nucleic acid probes as substrates.
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46.
  • Björnham, Oscar, 1976-, et al. (författare)
  • Measurements of the binding force between the Helicobacter pylori adhesin BabA and the Lewis b blood group antigen using optical tweezers
  • 2005
  • Ingår i: Journal of Biomedical Optics. - Bellingham, WA : SPIE-Intl Soc Optical Eng. - 1083-3668 .- 1560-2281. ; 10:4, s. 044024-044032
  • Tidskriftsartikel (refereegranskat)abstract
    • Helicobacter pylori is a world-wide spread bacterium that causes persistent infections and chronic inflammations that can develop into gastritis and peptic ulcer disease. It expresses several adhesin proteins on its surface that bind to specific receptors in the gastric epithelium. The most well-known adhesin is BabA, which has previously been shown to bind specifically to the fucosylated blood group antigen Lewis b (Leb). The adhesion forces between BabA and the Leb antigen are investigated in this work and assessed by means of optical tweezers. A model system for in situ measurements of the interaction forces between individual bacteria and beads coated with Leb is developed. It is found that the de-adhesion force in this model system, measured with a loading rate of ~100 pN/s, ranges from 20 to 200 pN. The de-adhesion force appears predominantly as multiples of an elementary force, which is determined to 25±1.5 pN and identified as the unbinding force of an individual BabA-Leb binding. It is concluded that adhesion in general is mediated by a small number of bindings (most often 1 to 4) despite that the contact surface between the bacterium and the bead encompassed significantly more binding sites.
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47.
  • Broos, Sissela, et al. (författare)
  • Synergistic augmentation of CD40-mediated activation of antigen-presenting cells by amphiphilic poly(γ-glutamic acid) nanoparticles.
  • 2012
  • Ingår i: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 33:26, s. 6230-6239
  • Tidskriftsartikel (refereegranskat)abstract
    • Agonistic anti-CD40 monoclonal antibodies (mAbs) hold great potential for cancer immunotherapy. However, systemic administration of anti-CD40 mAbs can be associated with severe side effects, such as cytokine release syndrome and liver damage. With the aim to increase the immunostimulatory potency as well as to achieve a local drug retention of anti-CD40 mAbs, we linked an agonistic mAb to immune activating amphiphilic poly(γ-glutamic acid) nanoparticles (γ-PGA NPs). We demonstrate that adsorption of anti-CD40 mAb to γ-PGA NPs (anti-CD40-NPs) improved the stimulatory capacity of the CD40 agonist, resulting in upregulation of costimulatory CD80 and CD86 on antigen-presenting cells, as well as IL-12 secretion. Interestingly, anti-CD40-NPs induced strong synergistic proliferative effects in B cells, possibly resulting from a higher degree of CD40 multimerization, enabled by display of multiple anti-CD40 mAbs on the NPs. In addition, local treatment with anti-CD40-NPs, compared to only soluble CD40 agonist, resulted in a significant reduction in serum levels of IL-6, IL-10, IL-12 and TNF-α in a bladder cancer model. Taken together, our results suggest that anti-CD40-NPs are capable of synergistically enhancing the immunostimulatory effect induced by the CD40 agonist, as well as minimizing adverse side effects associated with systemic cytokine release. This concept of nanomedicine could play an important role in localized immunotherapy of cancer.
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48.
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49.
  • Chen, Jingjing (författare)
  • Heat-transfer Enhancement for Slurries from Biogas Plants− Properties, processes, and thermal systems
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    •  Biomethane production from renewable residues with anaerobic digestion gains increasing attention as a crucial alternative to petroleum fuels. It has been vigorously developed, but the large amounts of subsidy from the government indicate that the process efficiency needs to be further improved. For biomethane production, on the one hand, a great amount of heat needs to be used for heating the feeding slurry, sanitation of slurry, and maintaining the temperature in the large-scale reactors. On the other hand, a large amount of thermophilic effluent slurries brings a huge amount of waste heat, which can be recovered. This makes it important to study how to increase production by improving the thermal efficiency of biogas plants with novel heat exchangers. The working fluids in the biogas plants are the non-Newtonian and high-viscous slurries, and the conventional heat exchangers in biogas plants always show much lower performance compared to those in other industries. Normally, the slurries in the biogas plant consist of different substrates, including straw, manure, food waste, municipal sludge, and their mixtures, and various factors such as the amount and type of solids, particle size, shear rate, and temperature impact the rheological properties of the slurries, which makes the complexity in the rheological properties and the difficulty in developing novel heat exchangers.The development of heat exchangers calls for the rheological properties of slurries. However, to the best of our knowledge, only the rheology of manure slurry was systematically determined and modeled considering the effect of temperature. The lack of the rheological properties of slurries further hinders the design and development of novel geometries to enhance the heat transfer of the slurries. Correspondingly, the quantitative contribution and potential of the waste-heat recovery from the slurries to production using the enhanced geometry remain unclear.     In this thesis work, to design novel geometry with heat-transfer enhancement for different slurries and determine its potential in thermal cycles in the full-scale biogas plants, firstly, the temperature-dependent rheological properties of the slurries, including the corn straw, food waste, and mixed slurries, were tested and modeled. It was found that these slurries possess strong shear-thinning behavior, the temperature has a significant impact on their dynamic viscosity, and the power-law model combined with the Arrhenius equation can describe the rheology well.    Subsequently, with the reliable models of the rheological properties as the key input,  Computational Fluid Dynamics simulations were conducted to screen different twisted geometries, determine the heat-transfer performance, and reveal the mechanism of the heat-transfer enhancement. Lab- and pilot-scale experiments were also conducted to validate the numerical results. The twisted hexagonal tubes show a positive enhancement factor up to 2.6 compared to normal heat exchangers in a wide range of operating conditions. The continuous and strong near-wall shear effect is the intrinsic reason for achieving a significant heat-transfer enhancement in the twisted hexagonal tubes. Moreover, the generalized engineering equations for predicting the effective shear rate and heat-transfer performance with measurable parameters were established and verified with both numerical and experimental results.    Finally, the twisted-hexagonal-tube heat exchange was integrated with complete thermal cycles, including waste-heat recovery and external heating processes in the biogas plant, and the potential of increased production and profits were modeled and analyzed combined with the practical operating conditions in a full-scale biogas plant. It was found that for the waste-heat recovery using the twisted hexagonal tubes, the net raw biogas production can increase by up to 17.0 %, and for the external heating process, the increased profit equivalent to 39 % of total production can be achieved owing to energy conservation in external heating using the twisted-hexagonal-tube heat exchangers for a full-scale biogas plant. 
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50.
  • Dainiak, Maria B, et al. (författare)
  • Gelatin-fibrinogen cryogel dermal matrices for wound repair: Preparation, optimisation and in vitro study.
  • 2010
  • Ingår i: Biomaterials. - : Elsevier BV. - 1878-5905 .- 0142-9612. ; 31, s. 67-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Macroporous sponge-like gelatin-fibrinogen (Gl-Fg) scaffolds cross-linked with different concentrations (0.05-0.5%) of glutaraldehyde (GA) were produced using cryogelation technology, which allows for the preparation of highly porous scaffolds without compromising their mechanical properties, and is a more cost-efficient process than freeze-drying. The produced Gl-Fg-GA(X) scaffolds had a uniform interconnected open porous structure with a porosity of up to 90-92% and a pore size distribution of 10-120mum. All of the obtained cryogels were elastic and mechanically stable, except for the Gl-Fg-GA(0.05) scaffolds. Swelling kinetics and degradation rate, but not the porous structure of the cryogels, were strongly dependent on the degree of cross-linking. A ten-fold increase in the degree of cross-linking resulted in an almost 80-fold decrease in the rate of degradation in a solution of protease. Cryogels were seeded with primary dermal fibroblasts and the densities observed on the surface, plus the expression levels of collagen types I and III observed 5 days post-seeding, were similar to those observed on a control dermal substitute material, Integra((R)). Fibroblast proliferation and migration within the scaffolds were relative to the GA content. Glucose consumption rate was 3-fold higher on Gl-Fg-GA(0.1) than on Gl-Fg-GA(0.5) cryogels 10 days post-seeding. An enhanced cell motility on cryogels with reducing GA crosslinking was obtained after long time culture. Particularly marked cell infiltration was seen in gels using 0.1% GA as a crosslinker. The scaffold started to disintegrate after 42 days of in vitro culturing. The described in vitro studies demonstrated good potential of Gl-Fg-GA(0.1) scaffolds as matrices for wound healing.
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