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  • 1.
    Aminlashgari, Nina
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Höglund, Odd V
    Borg, Niklas
    Hakkarainen, Minna
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Degradation profile and preliminary clinical testing of a resorbable device for ligation of blood vessels2013In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 9, no 6, p. 6898-904Article in journal (Refereed)
    Abstract [en]

    A resorbable device for ligation of blood vessels was developed and tested in vitro to reveal the degradation profile of the device and to predict the clinical performance in terms of adequate mechanical support during a healing period of I week. In addition, preliminary clinical testing was performed that showed complete hemostasis and good tissue grip of renal arteries in five pigs. The device was made by injection molding of poly(glycolide-co-trimethylene carbonate) triblock copolymer, and it consisted of a case with a locking mechanism connected to a partly perforated flexible band. A hydrolytic degradation study was carried out for 7, 30 and 60 days in water and buffer medium, following the changes in mass, water absorption, pH and mechanical properties. A new rapid matrix-free laser desorption ionization-mass spectrometry (LDI-MS) method was developed for direct screening of degradation products released into the degradation medium. The combination of LDI-MS and electrospray ionization-mass spectrometry analyses enabled the comparison of the degradation product patterns in water and buffer medium. The identified degradation products were rich in trimethylene carbonate units, indicating preferential hydrolysis of amorphous regions where trimethylene units are located. The crystallinity of the material was doubled after 60 days of hydrolysis, additionally confirming the preferential hydrolysis of trimethylene carbonate units and the enrichment of glycolide units in the remaining solid matrix. The mechanical performance of the perforated band was followed for the first week of hydrolysis and the results suggest that sufficient strength is retained during the healing time of the blood vessels.

  • 2.
    Beaussant Törne, Karin
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Khan, Fareed Ashraf
    Örnberg, A.
    Weissenrieder, Jonas
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Zn-Mg and Zn-Ag degradation mechanism under biologically relevant conditionsManuscript (preprint) (Other academic)
    Abstract [en]

    Zinc alloys form a promising new class of biodegradable metals that combine suitable mechanical properties with the favorable degradation properties of pure zinc. However, the current understanding of the influence of alloying elements on the corrosion of zinc alloys, in biologically relevant media, is limited. We studied the degradation of three alloys, Zn 4 wt% Ag, Zn 0.5 wt% Mg and Zn 3 wt% Mg by in situ electrochemical impedance spectroscopy (EIS). After exposure for 1h or 30 days the samples were characterized by infrared spectroscopy and scanning electron microscopy (SEM). The presence of secondary phases in the alloy microstructure induced selective corrosion and increased degradation rate. An increase in surface inhomogeneity was evident by EIS analysis both at short (hours) as well as long immersion times (days). The microgalvanic corrosion of the Zn-Ag alloy resulted in enrichment of the AgZn3 phase at the sample surface. The enrichment of Ag and potential release of AgZn3 particles may result in complications during the tissue regeneration. The Zn-Mg alloy surface was depleted of the Mg-rich phase after 8-12 days. The selective dissolution caused local precipitation of2corrosion products and a thicker corrosion layer with larger pore size consistent with increased corrosion rate.

  • 3.
    Beaussant Törne, Karin
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Örnberg, A.
    Weissenrieder, Jonas
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Characterization of the Protective Layer Formed on Zinc in Whole BloodManuscript (preprint) (Other academic)
    Abstract [en]

    The advantageous degradation properties of zinc in a biological environment are related to the presence of a protective corrosion layer composed of both organic and inorganic components. However, the mechanisms governing its formation and how the organic species influence its properties have not been established. Here we study the protective layer formation during anodic polarization in whole blood by in situ electrochemical impedance spectroscopy (EIS) as well as infrared spectroscopy and scanning electron microscopy. Simulated body fluid (m-SBF) was used as a reference media to discern the influence of the organic species present in whole blood. Protective zinc phosphate layers form on the Zn surface in both solutions, but of different nature and through diverse mechanisms. In m-SBF the passivating thin film formation occur already at open circuit potential, reducing the corrosion current compared to exposure in whole blood by a factor of 103. The high corrosion current in whole blood can be explained by a process including rapid protein adsorption preventing the initial formation of a protective phosphate layer. EIS analysis detected an inductive arc in whole blood at low overpotentials, before the onset of protective film formation, indicating the presence of adsorbed Zn2ions. The coverage of Zn ions approach 100% of the active surface at 110 mV. At this critical surface coverage a reaction between the adsorbed Zn ions and PO42- takes place which results in formation of a protective, porous, film of ~1 μm thickness. The inorganic component of the protective film formed in whole blood was characterized as Zn(PO4)2(OH)2·3H2O.

  • 4.
    Bjurhager, Ingela
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Gamstedt, E. Kristofer
    Keunecke, Daniel
    Niemz, Peter
    Berglund, Lars A.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Biocomposites. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Mechanical performance of yew (Taxus baccata L.) from a longbow perspective2013In: Holzforschung, ISSN 0018-3830, E-ISSN 1437-434X, Vol. 67, no 7, p. 763-770Article in journal (Refereed)
    Abstract [en]

    Yew (Taxus baccata L.) longbow was the preferred weapon in the Middle Ages until the emergence of guns. In this study, the tensile, compression, and bending properties of yew were investigated. The advantage of yew over the other species in the study was also confirmed by a simple beam model. The superior toughness of yew has the effect that a yew longbow has a higher range compared with bows made from other species. Unexpectedly, the mechanical performance of a bow made from yew is influenced by the juvenile-to-mature wood ratio rather than by the heartwood-to-sapwood ratio. A yew bow is predicted to have maximized performance at a juvenile wood content of 30-50%, and located at the concave side (the compressive side facing the bowyer). Here, the stiffness and yield stress in compression should be as high as possible.

  • 5.
    Chouhan, Dimple
    et al.
    Indian Inst Technol Guwahati, Dept Biosci & Bioengn, Biomat & Tissue Engn Lab, Gauhati 781039, Assam, India..
    Das, Piyali
    West Bengal Univ Anim & Fishery Sci, Dept Vet Surg & Radiol, Kolkata 700037, W Bengal, India..
    Thatikonda, Naresh
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Nandi, Samit K.
    West Bengal Univ Anim & Fishery Sci, Dept Vet Surg & Radiol, Kolkata 700037, W Bengal, India..
    Hedhammar, My
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Mandal, Biman B.
    Indian Inst Technol Guwahati, Dept Biosci & Bioengn, Biomat & Tissue Engn Lab, Gauhati 781039, Assam, India..
    Silkworm Silk Matrices Coated with Functionalized Spider Silk Accelerate Healing of Diabetic Wounds2019In: ACS Biomaterials Science and Engineering, ISSN 2373-9878, Vol. 5, no 7, p. 3537-3548Article in journal (Refereed)
    Abstract [en]

    Complex cutaneous wounds like diabetic foot ulcers represent a critical clinical challenge and demand a large-scale and low-cost strategy for effective treatment. Herein, we use a rabbit animal model to investigate efficacy of bioactive wound dressings made up of silk biomaterials. Nanofibrous mats of Antheraea assama silkworm silk fibroin (AaSF) are coated with various recombinant spider silk fusion proteins through silk-silk interactions to fabricate multifunctional wound dressings. Two different types of spider silk coatings are used to compare their healing efficiency: FN-4RepCT (contains a cell binding motif derived from fibronectin) and Lac-4RepCT (contains a cationic antimicrobial peptide from lactoferricin). AaSF mats coated with spider silk show accelerated wound healing properties in comparison to the uncoated mats. Among the spider silk coated variants, dual coating of FN-4RepCT and Lac-4RepCT on top of AaSF mat demonstrated better wound healing efficiency, followed by FN-4RepCT and Lac-4RepCT single coated counterparts. The in vivo study also reveals excellent skin regeneration by the functionalized silk dressings in comparison to commercially used Duoderm dressing and untreated wounds. The spider silk coatings demonstrate early granulation tissue development, re-epithelialization, and efficient matrix remodelling of wounds. The results thus validate potential of bioactive silk matrices in faster repair of diabetic wounds.

  • 6. Donius, Amalie E.
    et al.
    Liu, Andong
    KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Berglund, Lars A.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Biocomposites. KTH, School of Chemical Science and Engineering (CHE), Centres, Wallenberg Wood Science Center.
    Wegst, Ulrike G. K.
    Superior mechanical performance of highly porous, anisotropic nanocellulose-montmorillonite aerogels prepared by freeze casting2014In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 37, p. 88-99Article in journal (Refereed)
    Abstract [en]

    Directionally solidified nanofibrillated cellulose (NFC)-sodium-montmorillonite (MMT) composite aerogels with a honeycomb-like pore structure were compared with non-directionally frozen aerogels with equiaxed pore structure and identical composition and found to have superior functionalities. To explore structure-property correlations, three different aerogel compositions of 3 wt% MMT, and 0.4 wt%, 0.8 wt%, and 1.2 wt% NFC, respectively, were tested. Young's modulus, compressive strength and toughness were found to increase with increasing NFC content for both architectures. The modulus increased from 25.8 kPa to 386 kPa for the isotropic and from 2,13 MPa to 3.86 MPa for the anisotropic aerogels, the compressive yield strength increased from 3.3 kPa to 18.0 kPa for the isotropic and from 32.3 kPa to 52.5 kPa for the anisotropic aerogels, and the toughness increased from 6.3 kJ/m(3) to 24.1 kJ/m(3) for the isotropic and from 22.9 kJ/m(3) to 46.2 kJ/m(3) for the anisotropic aerogels. The great range of properties, which can be achieved through compositional as well as architectural variations, makes these aerogels highly attractive for a large range of applications, for which either a specific composition, or a particular pore morphology, or both are required. Finally, because NFC is flammable, gasification experiments were performed, which revealed that the inclusion of MMT increased the heat endurance and shape retention functions of the aerogels dramatically up to 800 degrees C while the mechanical properties were retained up to 300 degrees C.

  • 7.
    Dånmark, Staffan
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Finne-Wistrand, Anna
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Albertsson, Ann-Christine
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Patarroyo, Manuel
    Institutionen for Odontologi, Karolinska Institute.
    Mustafa, Kamal
    Insititutt for klinisk Odontologi, Medicinska och Odontologiska Fakulteten, Universitetet i Bergen, Norge.
    Integrin-mediated adhesion of human mesenchymal stem cells to extracellular matrix proteins adsorbed to polymer surfaces2012In: Biomedical Materials, ISSN 1748-6041, E-ISSN 1748-605X, Vol. 7, no 3, p. 035011-Article in journal (Refereed)
    Abstract [en]

    In vitro, degradable aliphatic polyesters are widely used as cell carriers for bone tissue engineering, despite their lack of biological cues. Their biological active surface is rather determined by an adsorbed layer of proteins from the surrounding media. Initial cell fate, including adhesion and proliferation, which are key properties for efficient cell carriers, is determined by the adsorbed layer of proteins. Herein we have investigated the ability of human bone marrow derived stem cells (hBMSC) to adhere to extracellular matrix (ECM) proteins, including fibronectin and vitronectin which are present in plasma and serum. hBMSC expressed integrins for collagens, laminins, fibronectin and vitronectin. Accordingly, hBMSC strongly adhered to these purified ECM proteins by using the corresponding integrins. Although purified fibronectin and vitronectin adsorbed to aliphatic polyesters to a lower extent than to cell culture polystyrene, these low levels were sufficient to mediate adhesion of hBMSC. It was found that plasma- and serum-coated polystyrene adsorbed significant levels of both fibronectin and vitronectin, and fibronectin was identified as the major adhesive component of plasma for hBMSC; however, aliphatic polyesters adsorbed minimal levels of fibronectin under similar conditions resulting in impaired cell adhesion. Altogether, the results suggest that the efficiency of aliphatic polyesters cell carriers could be improved by increasing their ability to adsorb fibronectin.

  • 8.
    Dånmark, Staffan
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Finne-Wistrand, Anna
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Edlund, Ulrica
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Albertsson, Ann-Christine
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Mustafa, Kamal
    Insititutt for klinisk Odontologi, Medicinska och Odontologiska Fakulteten, Universitetet i Bergen, Norge.
    Enhanced Osteoconductivity of Degradable co-Polyester Scaffolds through Covalent Immobilization of BMP-2Manuscript (preprint) (Other academic)
  • 9.
    Dånmark, Staffan
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Gladnikoff, Micha
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Frisk, Thomas
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Zelenina, Marina
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Mustafa, Kamal
    Insititutt for klinisk Odontologi, Medicinska och Odontologiska Fakulteten, Universitetet i Bergen, Norge.
    Russom, Aman
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Finne-Wistrand, Anna
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Development of Novel Microfluidic Device for Long-Term in situ Monitoring of Live Cells in 3-dimensional MatricesManuscript (preprint) (Other academic)
  • 10. Fadeel, B.
    et al.
    Fornara, A.
    Toprak, Muhammet S.
    KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Functional Materials, FNM.
    Bhattacharya, K.
    Keeping it real: The importance of material characterization in nanotoxicology2015In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 468, no 3, p. 498-503Article in journal (Refereed)
    Abstract [en]

    Nanomaterials are small and the small size and corresponding large surface area of nanomaterials confers specific properties, making these materials desirable for various applications, not least in medicine. However, it is pertinent to ask whether size is the only property that matters for the desirable or detrimental effects of nanomaterials? Indeed, it is important to know not only what the material looks like, but also what it is made of, as well as how the material interacts with its biological surroundings. It has been suggested that guidelines should be implemented on the types of information required in terms of physicochemical characterization of nanomaterials for toxicological studies in order to improve the quality and relevance of the published results. This is certainly a key issue, but it is important to keep in mind that material characterization should be fit-for-purpose, that is, the information gathered should be relevant for the end-points being studied.

  • 11. Ferraris, S.
    et al.
    Vitale, A.
    Bertone, E.
    Guastella, S.
    Cassinelli, C
    Pan, Jinshan
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Spriano, S.
    Multifunctional commercially pure titanium for the improvement of bone integration: Multiscale topography, wettability, corrosion resistance and biological functionalization2016In: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 60, p. 384-393Article in journal (Refereed)
    Abstract [en]

    The objects of this research are commercially pure titanium surfaces, with multifunctional behavior, obtained through a chemical treatment and biological functionalization. The explored surfaces are of interest for dental implants, in contact with bone, where several simultaneous and synergistic actions are needed, in order to get a fast and effective osseointegration. The here described modified surfaces present a layer of titanium oxide, thicker than the native one, with a multi-scale surface topography (a surface roughness on the nano scale, which can be overlapped to a micro or macro roughness of the substrate) and a high density of OH groups, that increase surface wettability, induce a bioactive behavior (hydroxyapatite precipitation in simulated body fluid) and make possible the grafting of biomolecules (alkaline phosphatase, ALP, in the present research). The surface oxide is an efficient barrier against corrosion, with passive behavior both with and without application of an external voltage.

  • 12.
    Ghorbani, Morteza
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging.
    Svagan, Anna Justina
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology.
    Grishenkov, Dmitry
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging. KTH, School of Engineering Sciences (SCI), Aeronautical and Vehicle Engineering, Marcus Wallenberg Laboratory MWL. Karolinska Institutet (KI), CLINTEC – Division of Medical Imaging and Technology.
    Acoustic Response of a Novel Class of Pickering Stabilized Perfluorodroplets2019Conference paper (Refereed)
    Abstract [en]

    Introduction

    Acoustic Droplet Vaporization (ADV) is a phase change phenomenon in which the liquid state, in the form of droplets, is converted to gas as a result of bursts in the excited ultrasound field. Having a wide range of medical applications, ADV has drawn considerable attention in imaging [1], diagnosis and critical medical treatment [2]. Therefore, benefitting from its broad potentials, with the consideration of its capability in localized noninvasive energy exposure, it is possible to utilize its effect in different medical applications from targeted drug delivery [3] to embolotherapy [4].

    Apart from the droplet characterization and ADV effectiveness on the applied region, the physics of ADV and particularly the ultrasound analysis is an essential parameter in the initiation of the vaporization. This part, which is related to acoustic wave physics, implies that ADV is mostly dependent on ultrasound pressure, frequency and temperature. In this sense, Miles et al. [5] tried to find incident negative pressure - called as ADV threshold- which is necessary for the induction of nucleation. It was successfully shown that the negative pressure required for the nucleation prior to collapse can be determined via perturbation analysis of a compressible inviscid flow around a droplet for various frequencies and diameters. In addition, the fluid medium which constitutes the droplet emulsion and the surrounding fluid constructs a significant field within ADV. In this regard, there are many studies which illustrated that the diameter of the droplets subjected to the acoustic waves undergoes a significant expansion of 5 to 6 times of their regular sizes [6-8].

    In this study, a new type of pickering stabilized perfluorodroplets (PFC) was examined under the effect of the different acoustic parameters to evaluate its potential in the acoustic droplet vaporization process. To assess the pressure effects on the stabilized droplets, the acoustic power within the ultrasound tests was varied and the phase trasnition was characterized according to the experimental conditions. Opticell® was utilized as the transparent device to visualize the droplets, which were exposed to the acoustic waves with the aid of the microscope and multi-well microplate.

    Methods

    Materials and emulsion preparation

    Perfluoropentane (PFC5) was purchased from Apollo Scientific (City, U.K.). Bleached sulfite pulp (from Nordic Paper Seffle AB, Sweden) was used in the production of the cationic cellulose nanofibers (CNFs). The CNF suspension (1.32 wt%) were prepared as described previously [9]. The CNFs had a dimension of 3.9 ± 0.8 nm in width and a length in the micrometer range. The amount of cationic groups was 0.13 mmol per g fiber, obtained from conductometric titration [9]. A suspension of CNF (0.28 wt%) was prepared by diluting the stock CNF with MilliQ-water (pH of diluted CNF suspension was 9.5). The suspension was treated with ultra-sonication at amplitude of 90% for 180 s (Sonics, Vibracell W750). The suspension was brought to room temperature. An amount of 36 g of the 0.28 wt% CNF suspension was mixed with 1 g of PFC5. The mixture was sonicated for 60s at an amplitude of 80% (under ice-cooling) to obtain the CNF-stabilized PFC5 droplets.

    The protocol for the acoustic tests

    100 μL of CNF-stabilized PFC5 droplets were added to 1900 μL of deionized water in order to prepare the solution which were exposed to the ultrasound waves. The droplet sample, diluted 1:19 in distilled water was introduced to the Opticell® and the acoustic waves at a fixed frequency and different powers were applied to the trageted area inside the Opticell® which is located inside a water bath. The ultrasound triggered sample then was placed under a 20X magnification objective of upright transmitted light microscope (ECLIPSE Ci-S, Nikon, Tokyo, Japan). 

    The acoustic tests were performed using high-power tone burst pulser-receiver (SNAP Mark IV,  Ritec, Inc., Warwick, RI, USA) equipped with a transducer (V382-SU Olympus NDT, Waltham, MA ) operating at the frequency of 3.5 MHz. The emulsion of CNF-stabilized PFC5 droplets were exposed to the power range which has the acsending trend from -30 to 0 dB at the given frequency. To investigate the droplet size variations at each power between, the droplets were collected inside the Opticell® and the droplet diameter was measured with the aid of the ImageJ software (version 1.50b, National institutes of health, USA) to determine the concentration and size distribution. The Gaussian distribution is ploted with mean value and standad deviation recover from the experimental data. An in-house image edge detection MATLAB™ script (MathWorks Inc., Natick, MA) were applied to analyze the images obtained from the microscope and provides the size and volume distributions.

    Results

    The size of PFP droplets is an important parameter to controll in the therapeutic applications. Here, a new type of Pickering stabilized perfluorodroplets were prepared where the PFP/water interface was stabilized with cellulose nanofibers (CNF) and the size of the droplets could easily be controlled by varying the amount of CNF added.  The resulting droplets were investigated using a single crystal transducer. Apart from the medical applications, controlling the droplet size is important from droplet dynamics point of view, becausethe interfacial energy is crucial in the assumption of the critical nucleus radius. Therefore, it is possible to estimate the negative peak pressure required for the phase transition once the droplet is controlled and interfacial energy deposited inside and on the surface of the droplet are balanced.

    According to the results in Figure 1, there is an appreciable rise of the size of the droplets after ultrasound waves exposure, particularly at -8 dB power. The experiments were performed for 30 seconds at different powers ranging from -30 to 0 dB, while the frequency was kept constant at 3.5 MHz, burst width in cycles was selected as 12 and repetition rate was set to 100. Images included in Figure 1 demonstrate major transitions in the intervals at -16, -8 and 0 dB. As shown in this figure, the droplet size increased with the power rise and more bubbles with bigger sizes appears at higher powers. This outcome implies the significant role of the applied frequency and power on the phase shift and subsequent mechanisms as a result of the acoustic wave exposure on the new nontoxic and incompatible droplet type.

    Figure 2 shows the average number of droplets and volume distribution at the corresponding powers to the Figure 1. It is shown that while the average diameter of the droplets is around 3.5 µm, the generated bubbles, as a result of the ADV, reaches up to 15 µm at the highest possible power. For each set of experiment (corresponding to a given power) 32 images were taken, thus, to reduce the errors and obtain the standard deviation (approximately 0.8 for all the cases), the presented diagrams for the droplet distributions exhibits the mean value for all of the acquired images. Therefore, it is shown that the droplet emulsion exhibited in NO US in Figure 2, which shows the regular view and distribution range of the CNF-stabilized PFC5 droplets at the room temperature, experiences ADV process with the diameter rise of about 5 times at the highest power when the frequency is fixed at 3.5 MHz.

    Conclusions

    The results show that there is appreciable rise on the size of the droplets after ultrasound waves exposure at a fixed frequency. Acoustic droplet vaporization (ADV) was illustrated at different powers for CNF-stabilized PFC5 droplets as a new class of pickering stabilized perfluorodroplets with the increase in the size of the droplets and following phase trasition to bubbles. Diameter increase of 5 times were obtained after the ultrasound exposure indicating the efficiency of the suggested droplets for the ADV process and therapeutic applications.   

    References

    [1] Arena CB, Novell A, Sheeran PS, Puett C, Moyer LC, Dayton PA, Dual-Frequency Acoustic Droplet Vaporization Detection for Medical Imaging 2015, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, 62: 9.

    [2] Kripfgans OD, Fowlkes JB, Miller DL, Eldevik OP, Carson PL, Acoustic droplet vaporization for therapeutic and diagnostic applications 2000, Ultrasound Med. Biol, 26:1177–1189.

    [3] Kang ST, Yeh CK, Intracellular Acoustic Droplet Vaporization in a Single Peritoneal Macrophage for Drug Delivery Applications 2011, Langmuir, 27:13183–13188.

    [4] Zhu M, Jiang L, Fabiilli ML, Zhang A, Fowlkes JB, Xu LX, Treatment of murine tumors using acoustic droplet vaporization-enhanced high intensity focused 2013, Ultrasound Phys. Med. Biol, 58:6179–6191.

    [5] Miles CJ, Doering CR, Kripfgans OD, Nucleation pressure threshold in acoustic droplet vaporization 2016, Journal of Applied Physics, 120:034903.

    [6] Sheeran PS, Wong VP, Luois S, McFarland RJ, Ross WD, Feingold S, Matsunaga TO, Dayton PA, Decafluorobutane as a phase-change contrast agent for low-energy extravascular ultrasonic imaging 2011, Ultrasound Med. Biol, 37:1518–1530.

    [7] Kripfgans OD, Fowlkes JB, Miller DL, Eldevik OP, Carson PL, Acoustic droplet vaporization for therapeutic and diagnostic applications 2000, Ultrasound Med. Biol, 26:1177–1189.

    [8] Kang S, Huang Y, Yeh C, Characterization of acoustic droplet vaporization for control of bubble generation under flow conditions 2014, Ultrasound Med. Biol, 40:551–561.

    [9] Svagan AJ, Benjamins JW, Al-Ansari Z, Shalom DB, Müllertz A, Wågberg L, Löbmann K, Solid cellulose nanofiber based foams–towards facile design of sustained drug delivery systems 2016, J. Control Release, 244:74–82 (Part A).

     

  • 13.
    Granskog, Viktor
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.
    García-Gallego, Sandra
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.
    von Kieseritzky, Johanna
    Department of Clinical Science and Education and the Department of Hand Surgery, Karolinska Institutet.
    Rosendahl, Jennifer
    RISE Research Institutes of Sweden, Bioscience and Materials–Medical Device Technology.
    Stenlund, Patrik
    RISE Research Institutes of Sweden, Bioscience and Materials–Medical Device Technology.
    Zhang, Yuning
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.
    Petronis, Sarunas
    RISE Research Institutes of Sweden, Bioscience and Materials–Medical Device Technology.
    Lyvén, Benny
    RISE Research Institutes of Sweden, Bioscience and Materials–Medical Device Technology.
    Arner, Marianne
    Department of Clinical Science and Education and the Department of Hand Surgery, Karolinska Institutet.
    Håkansson, Joakim
    RISE Research Institutes of Sweden, Bioscience and Materials–Medical Device Technology.
    Malkoch, Michael
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Coating Technology.
    High-Performance Thiol–Ene Composites Unveil a New Era of Adhesives Suited for Bone Repair2018In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 28, no 26, article id 1800372Article in journal (Refereed)
    Abstract [en]

    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 strengthis 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 bondstrength 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.

  • 14.
    Grytsan, Andrii
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Abdominal aortic aneurysm inception and evolution - A computational model2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Abdominal aortic aneurysm (AAA) is characterized by a bulge in the abdominal aorta. AAA development is mostly asymptomatic, but such a bulge may suddenly rupture, which is associated with a high mortality rate. Unfortunately, there is no medication that can prevent AAA from expanding or rupturing. Therefore, patients with detected AAA are monitored until treatment indication, such as maximum AAA diameter of 55 mm or expansion rate of 1 cm/year. Models of AAA development may help to understand the disease progression and to inform decision-making on a patient-specific basis. AAA growth and remodeling (G&R) models are rather complex, and before the challenge is undertaken, sound clinical validation is required.

    In Paper A, an existing thick-walled model of growth and remodeling of one layer of an AAA slice has been extended to a two-layered model, which better reflects the layered structure of the vessel wall. A parameter study was performed to investigate the influence of mechanical properties and G&R parameters of such a model on the aneurysm growth.

    In Paper B, the model from Paper A was extended to an organ level model of AAA growth. Furthermore, the model was incorporated into a Fluid-Solid-Growth (FSG) framework. A patient-specific geometry of the abdominal aorta is used to illustrate the model capabilities.

    In Paper C, the evolution of the patient-specific biomechanical characteristics of the AAA was investigated. Four patients with five to eight Computed Tomography-Angiography (CT-A) scans at different time points were analyzed. Several non-trivial statistical correlations were found between the analyzed parameters.

    In Paper D, the effect of different growth kinematics on AAA growth was investigated. The transverse isotropic in-thickness growth was the most suitable AAA growth assumption, while fully isotropic growth and transverse isotropic in-plane growth produced unrealistic results. In addition, modeling of the tissue volume change improved the wall thickness prediction, but still overestimated thinning of the wall during aneurysm expansion.

  • 15.
    Grytsan, Andrii
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Eriksson, Thomas S.E.
    Swedish Defence Research Agency.
    Watton, Paul N.
    Department of Computer Science, University of Sheffield, Sheffield, UK.
    Gasser, T. Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Growth description for vessel wall adaptation: a thick-walled mixture model of abdominal aortic aneurysm evolution2016Report (Other academic)
    Abstract [en]

    Modeling the soft tissue volumetric growth has received considerable attention in the literature.However, due to the lack of experimental observations, the growth kinematics, that are reported in the literature, are based on a number of assumptions.The present study tested the plausibility of different growth descriptions when applied to the abdominal aortic aneurysm (AAA) evolution.

    A structurally motivated material model and the multi-constituent tissue growth descriptions were utilized. The mass increment of the individual constituents preserved either the density or the volume.Four different growth descriptions were tested, namely isotropic (IVG), in-plane (PVG), in-thickness (TVG) growth and no volume growth (NVG) models.

    Based on the model sensitivity to the increased collagen deposition, TVG and NVG models were found to be plausible scenarios, while IVG and PVG were found to be implausible. In addition, TVG and NVG models were less sensitive to the initial constituent volume fractions, than IVG and PVG models.In conclusion, the choice of the growth kinematics is of crucial importance when modeling the AAA growth and remodeling, and,probably, also for other soft biological tissues.

  • 16.
    Gullfot, Fredrika
    KTH, School of Biotechnology (BIO), Glycoscience.
    Synthesis of xyloglucan oligo- and polysaccharides with glycosynthase technology2009Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Xyloglucans are polysaccharides found as storage polymers in seeds and tubers, and as cross-linking glycans in the cell wall of plants. Their structure is complex with intricate branching patterns, which contribute to the physical properties of the polysaccharide including its binding to and interaction with other glycans such as cellulose.

    Xyloglucan is widely used in bulk quantities in the food, textile and paper making industries. With an increasing interest in technically more advanced applications of xyloglucan, such as novel biocomposites, there is a need to understand and control the properties and interactions of xyloglucan with other compounds, to decipher the relationship between xyloglucan structure and function, and in particular the effect of different branching patterns. However, due to the structural heterogeneity of the polysaccharide as obtained from natural sources, relevant studies have not been possible to perform in practise. This fact has stimulated an interest in synthetic methods to obtain xyloglucan mimics and analogs with well-defined structure and decoration patterns.

    Glycosynthases are hydrolytically inactive mutant glycosidases that catalyse the formation of glycosidic linkages between glycosyl fluoride donors and glycoside acceptors. Since its first conception in 1998, the technology is emerging as a useful tool in the synthesis of large, complex polysaccharides. This thesis presents the generation and characterisation of glycosynthases based on xyloglucanase scaffolds for the synthesis of well-defined homogenous xyloglucan oligo- and polysaccharides with regular substitution patterns.

  • 17.
    Hansson, Jonas
    et al.
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Yasuga, Hiroki
    Basak, Sarthak
    Mercene Labs, Stockholm, SWEDEN.
    Carlborg, C. Fredrik
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Haraldsson, Tommy
    KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
    Direct Lithography of Rubbery OSTE+ Polymer2014In: Proceedings 18th International Conference on Miniaturized Systems for Chemistry and Life Sciences (MicroTAS2014), 14CBMS , 2014, p. 123-125Conference paper (Refereed)
    Abstract [en]

    We present a Rubbery, Off-Stoichiometric Thiol-Ene-epoxy (OSTE+) polymer for direct lithography manufacturing, demonstrate its use in pneumatic pinch microvalves for lab-on-chip applications, test the lithography process achieving pillars of aspect-ratios (a.r.) 1:8, and characterize it’s surface as hydrophilic.

  • 18.
    Hedberg, Yolanda
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Odnevall Wallinder, Inger
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Metal release and speciation of released chromium from a biomedical CoCrMo alloy into simulated physiologically relevant solutions2014In: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981, Vol. 102, no 4, p. 693-699Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to investigate the extent of released Co, Cr(III), Cr(VI), and Mo from a biomedical high-carbon CoCrMo alloy exposed in phosphate-buffered saline (PBS), without and with the addition of 10 mu M H2O2 (PBS + H2O2), and 10 g L-1 bovine serum albumin (PBS + BSA) for time periods up to 28 days. Comparative studies were made on AISI 316L for the longest time period. No Cr(VI) release was observed for any of the alloys in either PBS or PBS + H2O2 at open-circuit potential (no applied potential). However, at applied potentials (0.7 V vs. Ag/AgCl), Cr was primarily released as Cr(VI). Co was preferentially released from the CoCrMo alloy at no applied potential. As a consequence, Cr was enriched in the utmost surface oxide reducing the extent of metal release over time. This passivation effect was accelerated in PBS + H2O2. As previously reported for 316L, BSA may also enhance metal release from CoCrMo. However, this was not possible to verify due to the precipitation of metal-protein complexes with reduced metal concentrations in solution as a consequence. This was particularly important for Co-BSA complexes after sufficient time and resulted in an underestimation of metals in solution.

  • 19.
    Hedberg, Yolanda S.
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Qian, Bin
    Shen, Zhijian
    Virtanen, Sannakaisa
    Odnevall Wallinder, Inger
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    In vitro biocompatibility of CoCrMo dental alloys fabricated by selective laser melting2014In: Dental Materials, ISSN 0109-5641, E-ISSN 1879-0097, Vol. 30, no 5, p. 525-534Article in journal (Refereed)
    Abstract [en]

    Objective. Selective laser melting (SLM) is increasingly used for the fabrication of customized dental components made of metal alloys such as CoCrMo. The main aim of the present study is to elucidate the influence of the non-equilibrium microstructure obtained by SLM on corrosion susceptibility and extent of metal release (measure of biocompatibility). Methods. A multi-analytical approach has been employed by combining microscopic and bulk compositional tools with electrochemical techniques and chemical analyses of metals in biologically relevant fluids for three differently SLM fabricated CoCrMo alloys and one cast CoCrMo alloy used for comparison. Results. Rapid cooling and strong temperature gradients during laser melting resulted in the formation of a fine cellular structure with cell boundaries enriched in Mo (Co depleted), and suppression of carbide precipitation and formation of a martensitic epsilon (hcp) phase at the surface. These features were shown to decrease the corrosion and metal release susceptibility of the SLM alloys compared with the cast alloy. Unique textures formed in the pattern of the melting pools of the three different laser melted CoCrMo alloys predominantly explain observed small, though significant, differences. The susceptibility for corrosion and metal release increased with an increased number (area) of laser melt pool boundaries. Significance. This study shows that integrative and interdisciplinary studies of microstructural characteristics, corrosion, and metal release are essential to assess and consider during the design and fabrication of CoCrMo dental components of optimal biocompatibility. The reason is that the extent of metal release from CoCrMo is dependent on fabrication procedures.

  • 20. Issa, F.
    et al.
    Vervisch, V.
    Ottaviani, L.
    Szalkai, D.
    Vermeeren, L.
    Lyoussi, A.
    Kuznetsov, A.
    Lazar, M.
    Klix, A.
    Palais, O.
    Hallén, Anders
    KTH, School of Information and Communication Technology (ICT), Integrated Devices and Circuits.
    Improvements in Realizing 4H-SiC Thermal Neutron Detectors2016In: ISRD 15 - INTERNATIONAL SYMPOSIUM ON REACTOR DOSIMETRY, 2016, article id 05004Conference paper (Refereed)
    Abstract [en]

    In this work we presented two types of 4H-SiC semiconductor detectors (D1 and D2) both based on ion implantation of B-10 inside the aluminum metallic contact. The first detector shows a high leakage current after the implantation and low signal to noise ratio. However, improvements concerning the implantation parameters and the distance between the implanted B-10 thermal neutron converter layer and the active pn-junction have led to low leakage current and thus to higher signal to noise ratio. This proves the strength of this new method of realizing sensitive SiC-based thermal neutron detectors.

  • 21.
    Jensen, J.
    et al.
    Linkoping Univ, IFM, Thin Film Phys Div, SE-58183 Linkoping, Sweden..
    Sanz, R.
    CSIC, Inst Ciencia Mat Madrid, Madrid 28043, Spain..
    Jaafar, M.
    CSIC, Inst Ciencia Mat Madrid, Madrid 28043, Spain..
    Hernandez-Velez, M.
    CSIC, Inst Ciencia Mat Madrid, Madrid 28043, Spain.;Univ Autonoma Madrid, Appl Phys Dept, Madrid 28043, Spain..
    Asenjo, A.
    CSIC, Inst Ciencia Mat Madrid, Madrid 28043, Spain..
    Hallén, Anders
    KTH, School of Electrical Engineering and Computer Science (EECS), Electronics.
    Vazquez, M.
    Linkoping Univ, IFM, Thin Film Phys Div, SE-58183 Linkoping, Sweden..
    Localized Fe-56(+) Ion Implantation of TiO2 Using Anodic Porous Alumina2010In: ION BEAMS AND NANO-ENGINEERING / [ed] Ila, D Chu, PK Lindner, JKN Kishimoto, N Baglin, JEE, MATERIALS RESEARCH SOC , 2010, p. 3-+Conference paper (Refereed)
    Abstract [en]

    We present result following localized ion implantation of rutile titanium dioxide (TiO2) using anodic porous alumina as a mask. The implantation were performed with 100 keV Fe-56(+) ions using a fluence of 1.3.10(16) ions/cm(2). The surface modifications where studied by means of SEM, AFM/MFM and XRD. A well-defined hexagonal pattern of modified material in the near surface structure is observed. Local examination of the implanted areas revealed no clear magnetic signal. However, a variation in mechanical and electrostatic behavior between implanted and non-implanted zones is inferred from the variation in AFM signals.

  • 22. Karlsson, Johan
    et al.
    Harmankaya, Necati
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Palmquist, Anders
    Atefyekta, Saba
    Omar, Omar
    Tengvall, Pentti
    Andersson, Martin
    Stem cell homing using local delivery of plerixafor and stromal derived growth factor-1alpha for improved bone regeneration around Ti-implants2016In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, Vol. 104, no 10, p. 2466-2475Article in journal (Refereed)
    Abstract [en]

    Triggering of the early healing events, including the recruitment of progenitor cells, has been suggested to promote bone regeneration. In implantology, local drug release technologies could provide an attractive approach to promote tissue regeneration. In this study, we targeted the chemotactic SDF-1/CXCR4 axis that is responsible e.g. for the homing of stem cells to trauma sites. This was achieved by local delivery of plerixafor, an antagonist to CXCR4, and/or SDF-1, from titanium implants coated with mesoporous titania thin films with a pore size of 7.5 nm. In vitro drug delivery experiments demonstrated that the mesoporous coating provided a high drug loading capacity and controlled release. The subsequent in vivo study in rat tibia showed beneficial effects with respect to bone-implant anchorage and bone-formation along the surface of the implants when plerixafor and SDF-1 were delivered locally. The effect was most prominent by the finding that the combination of the drugs significantly improved the mechanical bone anchorage. These observations suggest that titanium implants with local delivery of drugs for enhanced local recruitment of progenitor cells have the ability to promote osseointegration. This approach may provide a potential strategy for the development of novel implant treatments.

  • 23. Kleinhans, C.
    et al.
    Mohan, R.R.
    Vacun, G.
    Schwarz, T.
    Haller, B.
    Sun, Yang
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Kahlig, A.
    Kluger, P.
    Finne-Wistrand, Anna
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Polymer Technology.
    Walles, H.
    Hansmann, J.
    A perfusion bioreactor system efficiently generates cell-loaded bone substitute materials for addressing critical size bone defects2015In: Biotechnology Journal, ISSN 1860-6768, E-ISSN 1860-7314, Vol. 10, no 11, p. 1727-1738Article in journal (Refereed)
    Abstract [en]

    Critical size bone defects and non-union fractions are still challenging to treat. Cell-loaded bone substitutes have shown improved bone ingrowth and bone formation. However, a lack of methods for homogenously colonizing scaffolds limits the maximum volume of bone grafts. Additionally, therapy robustness is impaired by heterogeneous cell populations after graft generation. Our aim was to establish a technology for generating grafts with a size of 10.5 mm in diameter and 25 mm of height, and thus for grafts suited for treatment of critical size bone defects. Therefore, a novel tailor-made bioreactor system was developed, allowing standardized flow conditions in a porous poly(L-lactide-co-caprolactone) material. Scaffolds were seeded with primary human mesenchymal stem cells derived from four different donors. In contrast to static experimental conditions, homogenous cell distributions were accomplished under dynamic culture. Additionally, culture in the bioreactor system allowed the induction of osteogenic lineage commitment after one week of culture without addition of soluble factors. This was demonstrated by quantitative analysis of calcification and gene expression markers related to osteogenic lineage. In conclusion, the novel bioreactor technology allows efficient and standardized conditions for generating bone substitutes that are suitable for the treatment of critical size defects in humans.

  • 24.
    Leino, Mattias
    et al.
    Tokyo Institute of Technology, Yokohama, Japan.
    Haque, Amranul
    Tokyo Institute of Technology, Yokohama, Japan and University of California, Davis, CA, USA.
    Adnan, Nihad
    Tokyo Institute of Technology, Yokohama, Japan.
    Akaike, Toshihiro
    Tokyo Institute of Technology, Yokohama, Japan.
    The effects of artificial E-cadherin matrix-induced embryonic stem cell scattering on paxillin and RhoA activation via a-catenin2014In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, no 6, p. 1797-1806Article in journal (Refereed)
    Abstract [en]

    Mechanical forces have been shown to affect stem cell behavior in a large array of ways. However, our understanding of how these mechanical cues may regulate the behavior of embryonic stem cells (ESCs) remains in its infancy. Here, we aim to clarify the effect of cell scattering on the regulation of Rho family GTPases Rac1 and RhoA as well as paxillin. Allowing ESCs to spread and scatter on a synthetically designed E-cadherin substratum causes phosphorylation of paxillin on consensus phosphorylation sites leading to activation of Rac1 and inactivation of RhoA. By culturing cells in presence of RhoA activator or growing cells to a highly confluent state reverses the effect of cell scattering phenotype. Knockdown of Ecadherin-adapter protein a-catenin revealed that it negatively affects paxillin phosphorylation and upregulates RhoA activity in compact cellular aggregates. Collectively these results indicate that cell scattering might cause a conformational change of a-catenin limiting its capacity to inhibit paxillin phosphorylation that causes an increase in Rac1 activation and RhoA deactivation. Understanding how synthetically designed extracellular matrix affect ESC signaling through mechanical cues brings a new aspect for stem cell engineers to develop technologies for controlling cell function.

  • 25.
    Neranon, Kitjanit
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Åslund, Mattias
    Draupner Innovations, Årsta, Sweden.
    Karalius, Antanas
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Yan, Min
    Xu, Hao
    KTH, School of Engineering Sciences (SCI), Applied Physics. Department of Applied Physics, Science for Life Laboratory.
    Fu, Ying
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Petermann, Ingemar
    Nanoelectronics, Acreo Swedish ICT AB, Kista, Sweden.
    Björk, Per
    Nanoelectronics, Acreo Swedish ICT AB, Kista, Sweden.
    Ramström, Olof
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Laser-induced, Surface Plasmon-enhanced Two-photon Excitation for Efficient Chemical Functionalization of Nanostructured Gold SurfacesManuscript (preprint) (Other academic)
  • 26.
    Nyberg, Tobias
    et al.
    Nippon Telegraph and Telephone Corporation.
    Shimada, Akiyoshi
    Nippon Telegraph and Telephone Corporation.
    Torimitsu, Keiichi
    Nippon Telegraph and Telephone Corporation.
    Ion conducting polymer microelectrodes for interfacing with neural networks2007In: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 160, no 1, p. 16-25Article in journal (Refereed)
    Abstract [en]

    We have examined the stimulation and recording properties of conjugated polymer microelectrode arrays as interfaces with neural networks of dissociated cortical cells. In particular the stimulation properties were investigated as a means of supplying a neural network with information. The stimulation efficiency at low stimulation voltages was evaluated and referenced to bare indium tin oxide (ITO) electrodes. The polymer electrodes were electrochemically polymerized from a blend of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS) and ethylenedioxythiophene (EDOT) onto ITO microelectrodes. Dissociated cortical cells were then plated on the electrodes and cultivated to form neural networks. Polymer electrode stimulation evoked a much greater response from the network than stimulation from ITO electrodes. Neural interfaces using polymer electrodes could be maintained for several months.

  • 27.
    Odeberg, Jacob
    et al.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. CytaCoat AB, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Hematol, Stockholm, Sweden..
    Wirsen, Anders
    CytaCoat AB, Stockholm, Sweden..
    Norberg, Ake
    CytaCoat AB, Stockholm, Sweden..
    Frie, Jakob
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Printz, Gordana
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Lagercrantz, Hugo
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Gudmundsson, Gudmundur H.
    Univ Iceland, Biomed Ctr, Reykjavik, Iceland..
    Agerberth, Birgitta
    CytaCoat AB, Stockholm, Sweden.;Karolinska Inst, Dept Lab Med, Huddinge, Sweden..
    Jonsson, Baldvin
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    A novel cysteine-linked antibacterial surface coating significantly inhibits bacterial colonization of nasal silicone prongs in a phase one pre-clinical trial2018In: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 93, p. 782-789Article in journal (Refereed)
    Abstract [en]

    Ventilator associated pneumonia and sepsis are frequent complications in neonatal care. Bacterial colonization of medical devices and interfaces used for respiratory support may contribute by functioning as a bacterial reservoir seeding bacteria into airways. We have developed an antibacterial surface coating based on a cysteine ligand covalently coupled via a spacer to a carboxylic backbone layer on an acrylic acid grafted silicone surface. This coating was applied on a commercially available nasal prong and the antibacterial effect was evaluated both in vitro and in vivo in a first-in-human phase 1 trial. The coated nasal prongs had strong antibacterial activity against both Gram-negative and Gram-positive bacteria in vitro. In a randomized pre-clinical trial study of 24 + 24 healthy adult volunteers who carried coated or non-coated nasal prongs for 18 h, a (10)log difference in mean bacterial colonization of 5.82 (p < 0.0001) was observed. These results show that this coating technique can prevent colonization by the normal skin and mucosal flora, and thus represent a promising novel technology for reduction of medical device-associated hospital acquired infections.

  • 28.
    Petrou, Georgia
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience.
    Investigating mucin interactions with diverse surfaces for biomedical applications2019Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Mucous membranes are covered with mucus, a viscoelastic hydrogel that plays an essential role in their protection from shear and pathogens. The viscoelasticity of mucus is owing to mucins, a group of densely glycosylated proteins. Mucins can interact with a wide range of surfaces; thus, there is big interest in exploring and manipulating such interactions for biomedical applications. This thesis presents investigations of mucin interactions with hydrophobic surfaces in order to identify the key features of mucin lubricity, as well as describes the development of materials that are optimized to interact with mucins.

     

    In Paper I we investigated the domains which make mucins outstanding boundary lubricants. The results showed that the hydrophobic terminal domains of mucins play a crucial role in the adsorption and lubrication on hydrophobic surfaces. Specifically, protease digestion of porcine gastric mucins and salivary mucins resulted in the cleavage of these domains and the loss of lubricity and surface adsorption. However, a “rescue” strategy was successfully carried out by grafting hydrophobic phenyl groups to the digested mucins and enhancing their lubricity. This strategy also enhanced the lubricity of polymers which are otherwise bad lubricants.

     

    In Paper II we developed mucoadhesive materials based on genetically engineered partial spider silk proteins. The partial spider silk protein 4RepCT was successfully functionalized with six lysines (pLys-4RepCT), or the Human Galectin-3 Carbohydrate Recognition Domain (hGal3-4RepCT). These strategies were aiming to either non-specific electrostatic interactions between the positive lysines and the negative mucins, or specific binding between the hGal3 and the mucin glycans. Coatings, fibers, meshes and foams were prepared from the new silk proteins, and the adsorption of porcine gastric mucins and bovine submaxillary mucins was measured, demonstrating enhanced adsorption.

     

    The work presented demonstrates how mucin-material interactions can provide us with valuable information for the development of new biomaterials. Specifically, mucin-based and mucin-inspired lubricants could provide desired lubrication to a wide range of surfaces, while our new silk based materials could be valuable tools for the development of mucosal dressings.

  • 29.
    Ramachandraiah, Harisha
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Kugiejko, Karol
    KTH, School of Biotechnology (BIO).
    Pettersson, Torbjörn
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Heuchel, Rainer
    Karolinska Institutet.
    Löhr, Matthias
    karolinska Institute.
    Hedhammar, My
    KTH, School of Biotechnology (BIO), Protein Technology.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Microfluidic based circulating tumor cell isolation and release from whole blood of pancreatic cancer patients using bio-functionalized recombinant spider silkManuscript (preprint) (Other academic)
    Abstract [en]

    A bio-functionalized microsystem was developed for the capture and release of cancer cells from whole blood. Effective isolation and purification of circulating tumor cells from whole blood provides important capability for clinical application and biological research. Here, we demonstrate a single step surface modification procedure for a microfluidic device based on self-assembly of recombinant spider silk harbouring an affinity domain for antibody binding. The surfaces of microfluidic devices were conjugated/equipped with anti-EpCAM antibody for selective isolation of pancreatic cancer cells from spiked whole blood and finally circulating tumor cells from pancreatic cancer patients. Moreover, a protease-cleavage site in the recombinant spider silk proteins provides the unique option to release the captured cancer cells on command from the device without compromising the cell’s viability. Our approach offers a simple, easy and robust surface modification process with a 85% cancer cell capture efficiency. Subsequent addition of a site-specific protease results in the release of 95% of captured cells from the bio functionalized microfluidic systems. 

  • 30.
    Ramachandraiah, Harisha
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Pettersson, Torbjörn
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Layer-by-layer system based cellulose nanofibrils for capture and release of cells in microfluidic deviceManuscript (preprint) (Other (popular science, discussion, etc.))
    Abstract [en]

    Selective isolation of cells, without inducing any phenotypic changes and maintaining cell viability will preserve the information necessary for down stream analysis. Here we present an ultra thin coating on the surface of disposable microfluidic device based on cellulose nanofibrils, that is modified to capture cells and for later release. Layer-by-layer technique facilitates the production of the thin coating of cellulose onto polymeric surfaces and modified to form affinity based cell capture surface. We demonstrate an  efficiently capture and release of cells, the release is done by selectively degrading 

  • 31.
    Safdari, Majid
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Applied Physical Chemistry.
    Fischer, Andreas C.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Applied Physical Chemistry.
    Xu, Bo
    KTH, School of Chemical Science and Engineering (CHE), Centres, Centre of Molecular Devices, CMD. KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Kloo, Lars
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Applied Physical Chemistry.
    Gardner, James M.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Applied Physical Chemistry.
    Erratum to: Structure and function relationships in alkylammonium lead(II) iodide solar cells2015In: Journal of Materials Chemistry A, ISSN 2050-7488, Vol. 3, no 17, p. 9317-9317Article in journal (Refereed)
  • 32. Salvo, P.
    et al.
    Henry, O. Y. F.
    Dhaenens, K.
    Acero Sanchez, J. L.
    Gielen, A.
    Werne Solnestam, Beata
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    O'Sullivan, C. K.
    Vanfleteren, J.
    Fabrication and functionalization of PCB gold electrodes suitable for DNA-based electrochemical sensing2014In: Bio-medical materials and engineering, ISSN 0959-2989, E-ISSN 1878-3619, Vol. 24, no 4, p. 1705-1714Article in journal (Refereed)
    Abstract [en]

    The request of high specificity and selectivity sensors suitable for mass production is a constant demand in medical research. For applications in point-of-care diagnostics and therapy, there is a high demand for low cost and rapid sensing platforms. This paper describes the fabrication and functionalization of gold electrodes arrays for the detection of deoxyribonucleic acid (DNA) in printed circuit board (PCB) technology. The process can be implemented to produce efficiently a large number of biosensors. We report an electrolytic plating procedure to fabricate low-density gold microarrays on PCB suitable for electrochemical DNA detection in research fields such as cancer diagnostics or pharmacogenetics, where biosensors are usually targeted to detect a small number of genes. PCB technology allows producing high precision, fast and low cost microelectrodes. The surface of the microarray is functionalized with self-assembled monolayers of mercaptoundodecanoic acid or thiolated DNA. The PCB microarray is tested by cyclic voltammetry in presence of 5 mM of the redox probe K3Fe(CN6) in 0.1 M KCl. The voltammograms prove the correct immobilization of both the alkanethiol systems. The sensor is tested for detecting relevant markers for breast cancer. Results for 5 nM of the target TACSTD1 against the complementary TACSTD1 and non-complementary GRP, MYC, SCGB2A1, SCGB2A2, TOP2A probes show a remarkable detection limit of 0.05 nM and a high specificity.

  • 33. Schizas, Nikos
    et al.
    Rojas, Ramiro
    Kootala, Sujit
    Andersson, Brittmarie
    Pettersson, Jennie
    Hilborn, Jons
    Hailer, Nils P
    Hyaluronic acid-based hydrogel enhances neuronal survival in spinal cord slice cultures from postnatal mice2013In: Journal of biomaterials applications, ISSN 0885-3282, E-ISSN 1530-8022, Vol. 28, no 6, p. 825-836Article in journal (Refereed)
    Abstract [en]

    Numerous biomaterials based on extracellular matrix-components have been developed. It was our aim to investigate whether a hyaluronic acid-based hydrogel improves neuronal survival and tissue preservation in organotypic spinal cord slice cultures. Organotypic spinal cord slice cultures were cultured for 4 days in vitro (div), either on hyaluronic acid-based hydrogel (hyaluronic acid-gel group), collagen gel (collagen group), directly on polyethylene terephthalate membrane inserts (control group), or in the presence of soluble hyaluronic acid (soluble hyaluronic acid group). Cultures were immunohistochemically stained against neuronal antigen NeuN and analyzed by confocal laser scanning microscopy. Histochemistry for choline acetyltransferance, glial fibrillary acidic protein, and Griffonia simplicifolia isolectin B4 followed by quantitative analysis was performed to assess motorneurons and different glial populations. Confocal microscopic analysis showed a 4-fold increase in the number of NeuN-positive neurons in the hyaluronic acid-gel group compared to both collagen (p < 0.001) and control groups (p < 0.001). Compared to controls, organotypic spinal cord slice cultures maintained on hyaluronic acid-based hydrogel showed 5.9-fold increased survival of choline acetyltransferance-positive motorneurons (p = 0.008), 2-fold more numerous resting microglial cells in the white matter (p = 0.031), and a 61.4% reduction in the number of activated microglial cells within the grey matter (p = 0.05). Hyaluronic acid-based hydrogel had a shear modulus (G′) of ≈1200 Pascals (Pa), which was considerably higher than the ≈25 Pa measured for collagen gel. Soluble hyaluronic acid failed to improve tissue preservation. In conclusion, hyaluronic acid-based hydrogel improves neuronal and - most notably - motorneuron survival in organotypic spinal cord slice cultures and microglial activation is limited. The positive effects of hyaluronic acid-based hydrogel may at least in part be due to its mechanical properties.

  • 34.
    Segerholm, Kristoffer
    KTH, School of Architecture and the Built Environment (ABE), Civil and Architectural Engineering.
    Wood Plastic Composites made from Modified Wood: Aspects on Moisture Sorption, Micromorphology and Durability2007Licentiate thesis, comprehensive summary (Other scientific)
    Abstract [en]

    Wood plastic composite (WPC) materials have seen a continuous market growth worldwide in the last decade. So-called extruded WPC profiles are today mainly used in outdoor applications, e.g. decking, railing and fencing. In outdoor conditions, moisture sorption in the wood component combined with temperature induced movements of the polymer matrix causes deformations of such composites. On the macroscopic scale this may lead to unacceptable warp, cup and bow of the WPC products, but on a microscopic scale, the movements will cause interfacial cracks between the particles and the matrix, resulting in little or no ability to transfer and re-distribute loads throughout the material. Moisture within the composite will also allow fungi and micro organisms to attack the wood particles.

    The conceptual idea of this work is to use a chemically modified wood component in WPCs to enhance their long term performance. These chemically modified wood particles exhibit reduced susceptibility to moisture, resulting in better dimensional stability and a higher resistance to biological degradation as compared to that of unmodified wood. The objective of this thesis is to study the effects of using modified wood in WPCs on their moisture sorption behaviour, micromorphology and microbiological durability. The modification methods used were acetylation, heat treatment and furfurylation.

    Equilibrium moisture content (EMC) and sorption behaviour of WPCs were determined by water vapour sorption experiments. The use of thin sections of the composites enabled EMC to be reached within a comparably short time span. The micromorphology was studied by LV-SEM (low vacuum-scanning electron microscope) using a specially designed sample preparation technique based on UV laser. The biological durability was evaluated by laboratory fungal test methods.

    The moisture sorption experiments showed lower moisture levels for all the composites when modified wood particles were used. This was also reflected in the micromorphological studies where pronounced wood-plastic interfacial cracks were formed due to moisture movement in the composites with unmodified wood particles. The sample preparation technique by UV laser proved to be a powerful tool for preparing surfaces for micromorphological studies without adding mechanical defects caused by the sample preparation technique itself. Results from the durability test showed that WPCs with modified wood particles are highly resistant to decay by fungi.

  • 35. Sommer, Gerhard
    et al.
    Schriefl, Andreas
    Zeindlinger, Georg
    Katzensteiner, Andreas
    Ainoedhofer, Herwig
    Saxena, Amulya
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Multiaxial mechanical response and constitutive modeling of esophageal tissues: Impact on esophageal tissue engineering2013In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 9, no 12, p. 9379-9391Article in journal (Refereed)
    Abstract [en]

    Congenital defects of the esophagus are relatively frequent, with 1 out of 2500 babies suffering from such a defect. A new method of treatment by implanting tissue engineered esophagi into newborns is currently being developed and tested using ovine esophagi. For the reconstruction of the biological function of native tissues with engineered esophagi, their cellular structure as well as their mechanical properties must be considered. Since very limited mechanical and structural data for the esophagus are available, the aim of this study was to investigate the multiaxial mechanical behavior of the ovine esophagus and the underlying microstructure. Therefore, uniaxial tensile, biaxial tensile and extension-inflation tests on esophagi were performed. The underlying microstructure was examined in stained histological sections through standard optical microscopy techniques. Moreover, the uniaxial ultimate tensile strength and residual deformations of the tissue were determined. Both the mucosa-submucosa and the muscle layers showed nonlinear and anisotropic mechanical behavior during uniaxial, biaxial and inflation testing. Cyclical inflation of the intact esophageal tube caused marked softening of the passive esophagi in the circumferential direction. The rupture strength of the mucosa-submucosa layer was much higher than that of the muscle layer. Overall, the ovine esophagus showed a heterogeneous and anisotropic behavior with different mechanical properties for the individual layers. The intact and layer-specific multiaxial properties were characterized using a well-known three-dimensional microstructurally based strain-energy function. This novel and complete set of data serves the basis for a better understanding of tissue remodeling in diseased esophagi and can be used to perform computer simulations of surgical interventions or medical-device applications.

  • 36.
    Stevens, Raoul
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.). Department of Biomedical Engineering, University of Technology, Eindhoven, The Netherlands.
    Grytsan, Andrii
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Biasetti, Jacopo
    Department of Mechanical Engineering, Johns Hopkins University, Baltimore, USA.
    Roy, Joy
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
    Lindquist Liljeqvist, Moritz
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
    Gasser, T.Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Biomechanical changes during abdominal aortic aneurysm growth2016Report (Refereed)
    Abstract [en]

    The biomechanics-based Abdominal Aortic Aneurysm (AAA) rupture risk assessment has gainedconsiderable scientific and clinical momentum. However, such studies have mainly focused oninformation at a single time point, and little is known about how AAA properties change over time.Consequently, the present study explored how geometry, wall stress-related and blood flow-relatedbiomechanical properties change during AAA expansion. Four patients with a total of 23 ComputedTomography-Angiography (CT-A) scans at different time points were analyzed. At each time point,patient-specific properties were extracted from (i) the reconstructed geometry, (ii) the computedwall stress at Mean Arterial Pressure (MAP), and (iii) the computed blood flow velocity atstandardized in and out flow conditions. Testing correlations between these parameters identifiedseveral non-intuitive dependencies. Most interestingly, the Peak Wall Rupture Index (PWRI) and themaximum Wall Shear Stress (WSS) independently predicted AAA volume growth. Similarly, Intra-luminal Thrombus (ILT) volume growth depended on both the maximum WSS and the ILT volumeitself. In addition, ILT volume, ILT volume growth and maximum ILT layer thickness correlated withPWRI as well as AAA volume growth. Consequently, a large ILT volume as well as fast increase of ILTvolume over time may be a risk factor for AAA rupture. However, tailored clinical studies would berequired to test this hypothesis and to clarify whether monitoring ILT development has any clinicalbenefit.

  • 37.
    Svagan, Anna
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Bio-inspired polysaccharide nanocomposites and foams2007Licentiate thesis, comprehensive summary (Other scientific)
    Abstract [en]

    Today, the majority of materials used for single-use packaging are petroleum-based synthetic polymers. With increased concern about the environmental protection, efforts have been made to develop alternative biodegradable materials from renewable resources. Starch offers an attractive alternative since it is of low cost and abundant. However, the starch material is brittle without plasticizer and the mechanical properties of starch materials are highly sensitive to moisture.

    In nature, the plant cell walls combine mechanical stiffness, strength and toughness despite a highly hydrated state. This interesting combination of properties is attributed to a network based on cellulose microfibrils. Inspired by this, microfibrillated cellulose (MFC) reinforced starch-based nanocomposites films and foams were prepared. Films with a viscous matrix and MFC contents from 10 to 70wt% were successfully obtained by solvent casting. The films were characterized by DSC, DMA, FE-SEM, XRD, mercury density measurements, and dynamic water vapor sorption (DVS). At 70wt% MFC content a high tensile strength together with high modulus and high work of fracture was observed. This was due to the nanofiber and matrix properties, favourable nanofiber-matrix interaction, a good dispersion of nanofibers and the MFC network.

    Novel nanocomposite foams were obtained by freeze-drying aquagels prepared from 8wt% solutions of amylopectin starch and MFC. The MFC content was varied from 10 to 70wt%. For composite foam with MFC contents up to 40wt%, improved mechanical properties were observed in compression. The mechanical properties depended both on the cell wall properties and the cell-structure of the foam. The effect of moisture (20-80% RH) on the dynamical properties of composite foam with 40wt% MFC was also investigated and compared to those of neat starch foam. Improved storage modulus was noted with MFC content, which was a result of the nanofiber network in the cell-wall. In addition, the moisture content decreased with MFC content, due to the less hydrophilic nature of MFC.

  • 38.
    Svagan, Anna
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Azizi Samir, My Ahmed Said
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Berglund, Lars
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Biomimetic polysaccharide nanocomposites of high cellulose content and high toughness2007In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 8, no 8, p. 2556-2563Article in journal (Refereed)
    Abstract [en]

    Plant cell walls combine mechanical stiffness, strength and toughness despite a highly hydrated state. Inspired by this, a nanostructured cellulose network is combined with an almost viscous polysaccharide matrix in the form of a 50/50 amylopectin-glycerol blend. Homogeneous films with a microfibrillated cellulose (MFC) nanofiber content in the range of 10-70 wt % are successfully cast. Characterization is carried out by dynamic mechanical analysis, field-emission scanning electron microscopy, X-ray diffraction, and mercury density measurements. The MFC is well dispersed and predominantly oriented random-in-the-plane. High tensile strength is combined with high modulus and very high work of fracture in the nanocomposite with 70 wt % WC. The reasons for this interesting combination of properties include nanofiber and matrix properties, favorable nanofiber-matrix interaction, good dispersion, and the ability of the MFC network to maintain its integrity to a strain of at least 8%.

  • 39.
    Thatikonda, Naresh
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Nilebäck, Linnea
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Kempe, Adam
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Widhe, Mona
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Hedhammar, My
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Bioactivation of Spider Silk with Basic Fibroblast Growth Factor for in Vitro Cell Culture: A Step toward Creation of Artificial ECM2018In: ACS Biomaterials Science and Engineering, ISSN 2373-9878, Vol. 4, no 9, p. 3384-3396Article in journal (Refereed)
    Abstract [en]

    Presentation of immobilized growth factors with retained bioactivity remains a challenge in the field of tissue engineering. In the present study, we propose a strategy to covalently conjugate a pleiotropic growth factor, basic fibroblast growth factor (bFGF) to a partial spider silk protein at gene level. The resulting silk-bFGF fusion protein has the propensity to self-assemble into silk-like fibers, and also surface coatings, as confirmed by quartz crystal microbalance studies. Functionality of the silk-bFGF coating to bind its cognate receptor was confirmed with surface plasmon resonance studies. As a step toward the creation of an artificial ECM, the silk-bFGF protein was mixed with FN-silk, an engineered spider silk protein with enhanced cell adhesive properties. Bioactivity of the thereby obtained combined silk was confirmed by successful culture of primary human endothelial cells on coatings and integrated within fibers, even in culture medium without supplemented growth factors. Together, these findings show that silk materials bioactivated with growth factors can be used for in vitro cell culture studies, and have potential as a tissue engineering scaffold.

  • 40.
    Turdalieva, Aizat
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Solandt, Johan
    AstraZeneca R and D; Sweden.
    Shambetova, Nestan
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Xu, Hao
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Blom, Hans
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Fu, Ying
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Bioelectric and Morphological Response of Liquid-Covered Human Airway Epithelial Calu-3 Cell Monolayer to Periodic Deposition of Colloidal 3-Mercaptopropionic-Acid Coated CdSe-CdS/ZnS Core-Multishell Quantum Dots2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 2, article id e0149915Article in journal (Refereed)
    Abstract [en]

    Lung epithelial cells are extensively exposed to nanoparticles present in the modern urban environment. Nanoparticles, including colloidal quantum dots (QDs), are also considered to be potentially useful carriers for the delivery of drugs into the body. It is therefore important to understand the ways of distribution and the effects of the various types of nanoparticles in the lung epithelium. We use a model system of liquid-covered human airway epithelial Calu-3 cell cultures to study the immediate and long-term effects of repeated deposition of colloidal 3-mercaptopropionic-acid coated CdSe-CdS/ZnS core-multishell QDs on the lung epithelial cell surface. By live confocal microscope imaging and by QD fluorescence measurements we show that the QD permeation through the mature epithelial monolayers is very limited. At the time of QD deposition, the transepithelial electrical resistance (TEER) of the epithelial monolayers transiently decreased, with the decrement being proportional to the QD dose. Repeated QD deposition, once every six days for two months, lead to accumulation of only small amounts of the QDs in the cell monolayer. However, it did not induce any noticeable changes in the long-term TEER and the molecular morphology of the cells. The colloidal 3-mercaptopropionic-acid coated CdSe-CdS/ZnS core-multishell QDs could therefore be potentially used for the delivery of drugs intended for the surface of the lung epithelia during limited treatment periods. © 2016 Turdalieva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

  • 41. Unterberger, M. J.
    et al.
    Schmoller, K. M.
    Bausch, A. R.
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    A new approach to model cross-linked actin networks: Multi-scale continuum formulation and computational analysis2013In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 22, p. 95-114Article in journal (Refereed)
    Abstract [en]

    The mechanical properties of a cell are defined mainly by the cytoskeleton. One contributor within this three-dimensional structure is the actin cortex which is located underneath the lipid bilayer. It forms a nearly isotropic and densely cross-linked protein network. We present a continuum mechanical formulation for describing the mechanical properties of in vitro model systems based on their micro-structure, i.e. the behavior of a single filament and its spatial arrangement. The network is considered elastic, viscous effects being neglected. Filamentous actin is a biopolymer with a highly nonlinear force-stretch relationship. This can be well described by a worm-like chain model that includes extensibility of the filament, which we call the . β-model. A comparison with experimental data shows good agreement with values for the physically interpretable parameters. To make these properties applicable to three dimensions we used a non-affine micro-sphere network, which accounts for filaments, equally distributed in space. The assembled model results in a strain-energy density which is a function of the deformation gradient, and it is validated with experimental data from rheological experiments of in vitro reconstituted actin networks. The Cauchy stress and elasticity tensors are obtained within the continuum mechanics framework and implemented into a finite element program to solve boundary-value problems.

  • 42. Vallhov, H.
    et al.
    Qin, Jian
    KTH, School of Information and Communication Technology (ICT), Material Physics (Closed 20120101), Functional Materials, FNM (Closed 20120101).
    Johansson, S.
    Muhammed, Mamoun Ali
    KTH, School of Information and Communication Technology (ICT), Material Physics (Closed 20120101), Functional Materials, FNM (Closed 20120101).
    Gabrielsson, S.
    Scheynius, A.
    The effect of gold nanoparticles on dendritic cells2006In: 2006 NSTI Nanotechnology Conference and Trade Show: NSTI Nanotech 2006 Technical Proceedings, 2006Conference paper (Refereed)
    Abstract [en]

    Gold is recognized as one of the most biocompatible and stable materials, and has been used for many years as a medical agent, among others in the form of salt for the treatment of rheumatoid arthritis [1]. More recent biological applications have been focusing on using gold nanoparticles for drug and gene delivery [2], or as a photothermal agent causing highly localized heating applicable in cancer therapy [3]. There is however very little information available concerning what influence such particles have on the immune system, e.g. on dendritic cells (DCs). DCs are present throughout the human body but are particularly localized at antigen-exposed sites, such as the skin. They are the most efficient type of antigen presenting cells having a capacity both to initiate primary and secondary immune responses, by expressing cytokines, MHC and co-stimulatory molecules such as CD80, CD83 and CD86 [4-5]. DCs decide whether an immune response should be initiated and are able to affect the development of T-helper cells into Treg-, Th1- or Th2-cells depending on their cytokines produced and their expression of co-stimulatory molecules [6]. We addressed the question whether spherical gold nanoparticles of 6 nm in diameter affect DCs, looking at morphology, viability, expression of cytokines and of co-stimulatory and antigen presenting molecules. This was assessed by using human monocyte derived DCs (myeloid DCs) and peripheral blood mononuclear cells from healthy blood donors together with gold nanoparticles [7], and various techniques including light microscopy, flow cytometry and ELISpot. After having overcome aggregation problems of gold nanoparticles by stabilizing with human serum albumin (HSA) and developed methods to produce nanoparticles with low lipopolysaccharide (LPS) contamination, experiments revealed that both morphology and viability were not affected by the gold nanoparticles. The expression of CD80, CD83, CD86 and MHC class II was only to a minor degree up-regulated after 6 and 24 h, and CD40 and MHC class I was not affected, which indicates biocompatibility of gold nanoparticles. This is further supported by low or no expression of the cytokines IL-10, IL-12 and IFN-alpha. HSA by itself did not have an effect on the DCs. In conclusion, gold nanoparticles of 6 nm in diameter are highly unlikely to initiate a danger signal to the immune system through the dendritic cells, and have therefore the potential to be used as inert carriers in biomedical applications.

  • 43. Xing, Zhe
    et al.
    Xue, Ying
    Finne-Wistrand, Anna
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Yang, Zhuang-Qun
    Mustafa, Kamal
    Copolymer cell/scaffold constructs for bone tissue engineering: Co-culture of low ratios of human endothelial and osteoblast-like cells in a dynamic culture system2013In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, Vol. 101A, no 4, p. 1113-1120Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare the effect of different ratios of human umbilical vein endothelial cells (HUVECs) on osteogenic activity of human osteoblast-like cells (HOB) and capillary-like structure (CLS), seeded into copolymer scaffolds in a dynamic culture system. HOB and HUVEC were co-cultured into poly(L-lactide)-co-(1,5-dioxepan-2-one) [poly(LLA-co-DXO)] scaffolds at ratios of 5:1 (5:1 group) and 2:1 (2:1 group). Samples were collected after 5, 15, and 25 days. Cross-sections were processed and the CLS from HUVEC was disclosed in both groups. Cell viability was determined by dsDNA assay. Cells seeded at the ratio of 5:1 had good viability. Total RNA was isolated and the reverse transcription reaction was performed. The influences on the expression of several osteogenic genes were various with regarding to different ratios of HUVEC demonstrated by the PCR array. The RT-PCR results was in consistent with the PCR array results that several osteogenesis related genes had higher expression in the 5:1 group than in the 2:1 group, especially at day 25, such as alkaline phosphatase, insulin-like growth factor 1 (IGF1), and so forth. ELISA showed that the production of IGF1 after 25 days of incubation were higher in cells co-cultured at the 5:1 ratio than at the 2:1 ratio. The results show that under dynamic culture conditions, co-culture of HOB with a low ratio of HUVEC in copolymer scaffolds results in CLS formation and significantly influenced the expression of osteogenic markers.

  • 44.
    Yan, Hong Ji
    et al.
    KTH. Uppsala Univ, Angstrom Lab, Dept Chem, SE-75121 Uppsala, Sweden.
    Casalini, Tommaso
    Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Inst Chem & Bioengn, Vladimir Prelog Weg 1, CH-8093 Zurich, Switzerland.;Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Inst Chem & Bioengn, Vladimir Prelog Weg 1, CH-8093 Zurich, Switzerland.;SUPSI, Dept Innovat Technol, Inst Mech Engn & Mat Technol, CH-6928 Manno, Switzerland..
    Hulsart-Billstrom, Gry
    Uppsala Univ, Dept Orthoped, Uppsala, Sweden..
    Wang, Shujiang
    Uppsala Univ, Angstrom Lab, Dept Chem, SE-75121 Uppsala, Sweden..
    Oommen, Oommen P.
    Tampere Univ Technol, Bioengn & Nanomed Lab, Fac Biomed Sci & Engn, Tampere 33720, Finland.;Tampere Univ Technol, Biomeditech Inst, Tampere 33720, Finland..
    Salvalaglio, Matteo
    UCL, Thomas Young Ctr, London WC1E 7JE, England.;UCL, Dept Chem Engn, London WC1E 7JE, England..
    Larsson, Sune
    Uppsala Univ, Dept Orthoped, Uppsala, Sweden..
    Hilborn, Jons
    Uppsala Univ, Angstrom Lab, Dept Chem, SE-75121 Uppsala, Sweden..
    Varghese, Oommen P.
    Uppsala Univ, Angstrom Lab, Dept Chem, SE-75121 Uppsala, Sweden..
    Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation2018In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 161, p. 190-202Article in journal (Refereed)
    Abstract [en]

    Synthetic scaffolds that possess an intrinsic capability to protect and sequester sensitive growth factors is a primary requisite for developing successful tissue engineering strategies. Growth factors such as recombinant human bone morphogenetic protein-2 (rhBMP-2) is highly susceptible to premature degradation and to provide a meaningful clinical outcome require high doses that can cause serious side effects. We discovered a unique strategy to stabilize and sequester rhBMP-2 by enhancing its molecular interactions with hyaluronic acid (HA), an extracellular matrix (ECM) component. We found that by tuning the initial protonation state of carboxylic acid residues of HA in a covalently crosslinked hydrogel modulate BMP-2 release at physiological pH by minimizing the electrostatic repulsion and maximizing the Van der Waals interactions. At neutral pH, BMP-2 release is primarily governed by Fickian diffusion, whereas at acidic pH both diffusion and electrostatic interactions between HA and BMP-2 become important as confirmed by molecular dynamics simulations. Our results were also validated in an in vivo rat ectopic model with rhBMP-2 loaded hydrogels, which demonstrated superior bone formation with acidic hydrogel as compared to the neutral counterpart. We believe this study provides new insight on growth factor stabilization and highlights the therapeutic potential of engineered matrices for rhBMP-2 delivery and may help to curtail the adverse side effects associated with the high dose of the growth factor.

  • 45. Yassin, Mohammed A.
    et al.
    Leknes, Knut N.
    Pedersen, Torbjorn O.
    Xing, Zhe
    Sun, Yang
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Lie, Stein A.
    Finne-Wistrand, Anna
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Mustafa, Kamal
    Cell seeding density is a critical determinant for copolymer scaffolds-induced bone regeneration2015In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, Vol. 103, no 11, p. 3649-3658Article in journal (Refereed)
    Abstract [en]

    Constructs intended for bone tissue engineering (TE) are influenced by the initial cell seeding density. Therefore, the objective of this study was to determine the effect of bone marrow stromal stem cells (BMSCs) density loaded onto copolymer scaffolds on bone regeneration. BMSCs were harvested from rat's bone marrow and cultured in media with or without osteogenic supplements. Cells were seeded onto poly(l-lactide-co-epsilon-caprolactone) [poly(LLA-co-CL)] scaffolds at two different densities: low density (1 x 10(6) cells/scaffold) or high density (2 x 10(6) cells/scaffold) using spinner modified flasks and examined after 1 and 3 weeks. Initial attachment and spread of BMSC onto the scaffolds was recorded by scanning electron microscopy. Cell proliferation was assessed by DNA quantification and cell differentiation by quantitative real-time reverse transcriptase-polymerized chain reaction analysis (qRT-PCR). Five-millimeter rat calvarial defects (24 defects in 12 rats) were implanted with scaffolds seeded with either low or high density expanded with or without osteogenic supplements. Osteogenic supplements significantly increased cell proliferation (p < 0.001). Scaffolds seeded at high cell density exhibited higher mRNA expressions of Runx2 p=0.001, Col1 p=0.001, BMP2 p<0.001, BSP p<0.001, and OC p=0.013. More bone was formed in response to high cell seeding density (p=0.023) and high seeding density with osteogenic medium (p=0.038). Poly (LLA-co-CL) scaffolds could be appropriate candidates for bone TE. The optimal number of cells to be loaded onto scaffolds is critical for promoting Extracellular matrix synthesis and bone formation. Cell seeding density and osteogenic supplements may have a synergistic effect on the induction of new bone.

  • 46. Ye, Fei
    et al.
    Barrefelt, Asa
    Asem, Heba
    Abedi-Valugerdi, Manuchehr
    El-Serafi, Ibrahim
    Saghafian, Maryam
    Abu-Salah, Khalid
    Alrokayan, Salman
    Muhammed, Mamoun
    KTH, School of Information and Communication Technology (ICT), Materials- and Nano Physics, Functional Materials, FNM.
    Hassan, Moustapha
    Biodegradable polymeric vesicles containing magnetic nanoparticles, quantum dots and anticancer drugs for drug delivery and imaging2014In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, no 12, p. 3885-3894Article in journal (Refereed)
    Abstract [en]

    We have developed biodegradable polymeric vesicles as a nanocarrier system for multimodal bioimaging and anticancer drug delivery. The poly(lactic-co-glycolic acid) (PLGA) vesicles were fabricated by encapsulating inorganic imaging agents of superparamagnetic iron oxide nanoparticles (SPION), manganese-doped zinc sulfide (Mn:ZnS) quantum dots (QDs) and the anticancer drug busulfan into PLGA nanoparticles via an emulsion-evaporation method. T-2(*)-weighted magnetic resonance imaging (MRI) of PLGA-SPION-Mn:ZnS phantoms exhibited enhanced negative contrast with r(2)(*) relaxivity of approximately 523 s(-1) mM(-1) Fe. Murine macrophage (J774A) cellular uptake of PLGA vesicles started fluorescence imaging at 2 h and reached maximum intensity at 24 h incubation. The drug delivery ability of PLGA vesicles was demonstrated in vitro by release of busulfan. PLGA vesicle degradation was studied in vitro, showing that approximately 32% was degraded into lactic and glycolic acid over a period of 5 weeks. The biodistribution of PLGA vesicles was investigated in vivo by MRI in a rat model. Change of contrast in the liver could be visualized by MRI after 7 min and maximal signal loss detected after 4 h post-injection of PLGA vesicles. Histological studies showed that the presence of PLGA vesicles in organs was shifted from the lungs to the liver and spleen over time.

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