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  • 1.
    Elhami Nik, Farzad
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Department of Electronics, Information and Bioengineering, Politecnico di Milano.
    Matthiesen, Isabelle
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. AIMES, Department of Neuroscience, Karolinska Institute.
    Winkler, Thomas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Low-Cost PVD Shadow Masks with Submillimeter Resolution from Laser-Cut Paper2020In: Micromachines, E-ISSN 2072-666X, Vol. 11, no 7, article id 676Article in journal (Refereed)
    Abstract [en]

    We characterize an affordable method of producing stencils for submillimeter physical vapor deposition (PVD) by using paper and a benchtop laser cutter. Patterning electrodes or similar features on top of organic or biological substrates is generally not possible using standard photolithography. Shadow masks, traditionally made of silicon-based membranes, circumvent the need for aggressive solvents but suffer from high costs. Here, we evaluate shadow masks fabricated by CO2 laser processing from quantitative filter papers. Such papers are stiff and dimensionally stable, resilient in handling, and cut without melting or redeposition. Using two exemplary interdigitated electrode designs, we quantify the line resolution achievable with both high-quality and standard lenses, as well as the positional accuracy across multiple length scales. Additionally, we assess the gap between such laser-cut paper masks and a substrate, and quantify feature reproduction onto polycarbonate membranes. We find that ~100 µm line widths are achievable independent of lens type and that average positional accuracy is better than ±100 µm at 4”-wafer scale. Although this falls well short of the micron-size features achievable with typical shadow masks, resolution in the tenths to tens of millimeters is entirely sufficient for applications from contact pads to electrochemical cells, allowing new functionalities on fragile materials.

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  • 2.
    Jury, Michael
    et al.
    Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics, Chemistry and Biology Linköping University Linköping 581 83 Sweden.
    Matthiesen, Isabelle
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Rasti Boroojeni, Fatemeh
    Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics, Chemistry and Biology Linköping University Linköping 581 83 Sweden.
    Ludwig, Saskia
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Civitelli, Livia
    Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics, Chemistry and Biology Linköping University Linköping 581 83 Sweden;Nuffield Department of Clinical Neurosciences John Radcliffe Hospital West Wing University of Oxford Oxford OX3 9DU UK.
    Winkler, Thomas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Institute of Microtechnology Center of Pharmaceutical Engineering Technische Universität Braunschweig Braunschweig 38106 Germany.
    Selegård, Robert
    Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics, Chemistry and Biology Linköping University Linköping 581 83 Sweden.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. AIMES, Center for Integrated Medical and Engineering Science Department of Neuroscience Karolinska Institute Solna 171 65 Sweden;Division of Nanobiotechnology Department of Protein Science, Science for Life Laboratory KTH Royal Institute of Technology Stockholm 17165 Sweden.
    Aili, Daniel
    Laboratory of Molecular Materials Division of Biophysics and Bioengineering Department of Physics, Chemistry and Biology Linköping University Linköping 581 83 Sweden.
    Bioorthogonally Cross‐Linked Hyaluronan–Laminin Hydrogels for 3D Neuronal Cell Culture and Biofabrication2022In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 11, no 11, article id 2102097Article in journal (Refereed)
    Abstract [en]

    Laminins (LNs) are key components in the extracellular matrix of neuronal tissues in the developing brain and neural stem cell niches. LN-presenting hydrogels can provide a biologically relevant matrix for the 3D culture of neurons toward development of advanced tissue models and cell-based therapies for the treatment of neurological disorders. Biologically derived hydrogels are rich in fragmented LN and are poorly defined concerning composition, which hampers clinical translation. Engineered hydrogels require elaborate and often cytotoxic chemistries for cross-linking and LN conjugation and provide limited possibilities to tailor the properties of the materials. Here a modular hydrogel system for neural 3D cell cultures, based on hyaluronan and poly(ethylene glycol), that is cross-linked and functionalized with human recombinant LN-521 using bioorthogonal copper-free click chemistry, is shown. Encapsulated human neuroblastoma cells demonstrate high viability and grow into spheroids. Long-term neuroepithelial stem cells (lt-NES) cultured in the hydrogels can undergo spontaneous differentiation to neural fate and demonstrate significantly higher viability than cells cultured without LN. The hydrogels further support the structural integrity of 3D bioprinted structures and maintain high viability of bioprinted and syringe extruded lt-NES, which can facilitate biofabrication and development of cell-based therapies.

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  • 3.
    Matthiesen, Isabelle
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Recreating the microenvironment of the neurovascular unit2022Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The neurovascular unit (NVU) comprises the blood-brain-barrier (BBB) and its surrounding astrocytes, pericytes and neurons that are embedded in the extracellular matrix (ECM). As the main function of the BBB is to protect the brain from inlet of pathogens and toxins, the specialized endothelial cells that keep the barrier tight will also hinder the passage of pharmaceuticals. Understanding the detailed microenvironment and cellular interactions involved in the development of the neurovascular unit is, therefore, an important step towards designing CNS-targeting pharmaceuticals that can pass into the brain. At the same time, the initial steps of pharmaceutical development often involve the use of animal based in vitro models with poor human translation; thus, there is a great need for novel methods to better mimic the complexity of the human NVU. Apart from conventional cell culture models, the use of micro-engineered devices, microphysiological systems (MPS), have gained popularity. The use of MPS allows for fabrication of tissue-like structures using stem cells and provide more in vivo-like parameters in terms of physical cues and dynamic flow. Various materials have been explored for chip fabrication, and biological and synthetic ECM-mimicking hydrogels have been developed for cell encapsulation. Unfortunately, models developed to date often lack either: i) relevant and reproducible cell sources, ii) materials that allow for easy chip fabrication where sensors can be integrated to understand metabolic effects and barrier integrity, or iii) animal-free defined ECM-mimicking scaffolds that support the culture of sensitive cells. This thesis presents an isogenic model of the BBB using iPSC-derived endothelial cells and astrocytes cultured in a MPS made from the non-absorbing polymer OSTE+ that allows for easy fabrication and integration of interdigitated gold electrodes for continuous barrier integrity monitoring. The model presents barrier-protective effects of the BBB-penetrating drug NACA. To better understand the metabolic attributes of astrocytes, a flow-cell sensor is evaluated for the measurement of glucose and lactate turnover during a ketogenic diet. The results imply that such a sensor is valuable for the measurement of metabolic changes and can, in the future, be integrated into MPSs.Furthermore, a model of early neuronal development is realized by using defined copper-free click chemistry to conjugate laminin to a hyaluronic-based hydrogel system for the differentiation of neuroepithelial stem cells. The use of the hydrogel is validated for bioprinting, and the first-ever printed neuroepithelial stem cells are presented. In another study astrocyte 3D culture and bioprinting is evaluated in peptide conjugated hyaluronic-based hydrogels. Unique attachment and spreading of human fetal astrocytes is observed while the common glioblastoma U87 cells display a rounded up morphology. The results of the hydrogel study imply that the defined chemistry of the hydrogel is suitable for both neuroepithelial stem cells, U87 and fetal primary astrocytes, and can in the future be integrated into MPS to circumvent the use of animal derived matrices. In summary, these results provide solutions to some of the problems to date and lay the ground work for the continuation of the development of human-relevant MPS of the NVU.

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  • 4.
    Matthiesen, Isabelle
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. AstraZeneca, CVRM Safety, Clin Pharmacol & Safety Sci, R&D, Gothenburg, Sweden..
    Jury, Michael
    Linköping Univ, Dept Phys Chem & Biol, Div Biophys & Bioengn, Lab Mol Mat, S-58183 Linköping, Sweden..
    Rasti Boroojeni, Fatemeh
    Linköping Univ, Dept Phys Chem & Biol, Div Biophys & Bioengn, Lab Mol Mat, S-58183 Linköping, Sweden..
    Ludwig, Saskia
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Holzreuter, Muriel
    Karolinska Inst, Ctr Integrated Med & Engn Sci, Dept Neurosci, AIMES, Solna, Sweden..
    Buchmann, Sebastian
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Karolinska Inst, Ctr Integrated Med & Engn Sci, Dept Neurosci, AIMES, Solna, Sweden.;KTH Royal Inst Technol, Dept Prot Sci, Div Nanobiotechnol, Sci Life Lab, Solna, Sweden..
    Aman Trager, Andrea
    Linköping Univ, Dept Phys Chem & Biol, Div Biophys & Bioengn, Lab Mol Mat, S-58183 Linköping, Sweden..
    Selegard, Robert
    Linköping Univ, Dept Phys Chem & Biol, Div Biophys & Bioengn, Lab Mol Mat, S-58183 Linköping, Sweden..
    Winkler, Thomas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Tech Univ Carolo Wilhelmina Braunschweig, Inst Microtechnol, Braunschweig, Germany.;Tech Univ Carolo Wilhelmina Braunschweig, Ctr Pharmaceut Engn, Braunschweig, Germany..
    Aili, Daniel
    Linköping Univ, Dept Phys Chem & Biol, Div Biophys & Bioengn, Lab Mol Mat, S-58183 Linköping, Sweden..
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Karolinska Inst, Ctr Integrated Med & Engn Sci, Dept Neurosci, AIMES, Solna, Sweden.;KTH Royal Inst Technol, Dept Prot Sci, Div Nanobiotechnol, Sci Life Lab, Solna, Sweden..
    Astrocyte 3D culture and bioprinting using peptide functionalized hyaluronan hydrogels2023In: Science and Technology of Advanced Materials, ISSN 1468-6996, E-ISSN 1878-5514, Vol. 24, no 1, article id 2165871Article in journal (Refereed)
    Abstract [en]

    Astrocytes play an important role in the central nervous system, contributing to the development of and maintenance of synapses, recycling of neurotransmitters, and the integrity and function of the blood-brain barrier. Astrocytes are also linked to the pathophysiology of various neurodegenerative diseases. Astrocyte function and organization are tightly regulated by interactions mediated by the extracellular matrix (ECM). Engineered hydrogels can mimic key aspects of the ECM and can allow for systematic studies of ECM-related factors that govern astrocyte behaviour. In this study, we explore the interactions between neuroblastoma (SH-SY5Y) and glioblastoma (U87) cell lines and human fetal primary astrocytes (FPA) with a modular hyaluronan-based hydrogel system. Morphological analysis reveals that FPA have a higher degree of interactions with the hyaluronan-based gels compared to the cell lines. This interaction is enhanced by conjugation of cell-adhesion peptides (cRGD and IKVAV) to the hyaluronan backbone. These effects are retained and pronounced in 3D bioprinted structures. Bioprinted FPA using cRGD functionalized hyaluronan show extensive and defined protrusions and multiple connections between neighboring cells. Possibilities to tailor and optimize astrocyte-compatible ECM-mimicking hydrogels that can be processed by means of additive biofabrication can facilitate the development of advanced tissue and disease models of the central nervous system.

  • 5.
    Matthiesen, Isabelle
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Jury, Michael
    Rasti Boroojeni, Fatemeh
    Ludwig, Saskia L.
    Holzreuter, Muriel
    Buchmann, Sebastian
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Selegård, Robert
    Winkler, Thomas E.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Aili, Daniel
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Astrocyte 3D Culture and Bioprinting using Peptide Functionalized Hyaluronan HydrogelsManuscript (preprint) (Other academic)
  • 6.
    Matthiesen, Isabelle
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. AstraZeneca, R&D, Clin Pharmacol & Safety Sci, CVRM Safety, S-43150 Gothenburg, Sweden..
    Nasiri, Rohollah
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. Karolinska Inst, Ctr Adv Integrated Med & Engn Sci, Dept Neurosci, AIMES, S-17177 Solna, Sweden..
    Orrego, Alessandra Tamashiro
    KTH. Sci Life Lab, S-17165 Solna, Sweden..
    Winkler, Thomas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. Institute of Microtechnology Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Braunschweig, 38106, Germany.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. KTH, Centres, Center for the Advancement of Integrated Medical and Engineering Sciences, AIMES. KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. Department of Neuroscience, Karolinska Institute, 17177 Solna, Sweden..
    Metabolic Assessment of Human Induced Pluripotent Stem Cells-Derived Astrocytes and Fetal Primary Astrocytes: Lactate and Glucose Turnover2022In: Biosensors, ISSN 2079-6374, Vol. 12, no 10, p. 839-, article id 839Article in journal (Refereed)
    Abstract [en]

    Astrocytes represent one of the main cell types in the brain and play a crucial role in brain functions, including supplying the energy demand for neurons. Moreover, they are important regulators of metabolite levels. Glucose uptake and lactate production are some of the main observable metabolic actions of astrocytes. To gain insight into these processes, it is essential to establish scalable and functional sources for in vitro studies of astrocytes. In this study, we compared the metabolic turnover of glucose and lactate in astrocytes derived from human induced pluripotent stem cell (hiPSC)-derived Astrocytes (hiAstrocytes) as a scalable astrocyte source to human fetal astrocytes (HFAs). Using a user-friendly, commercial flow-based biosensor, we could verify that hiAstrocytes are as glycogenic as their fetal counterparts, but their normalized metabolic turnover is lower. Specifically, under identical culture conditions in a defined media, HFAs have 2.3 times higher levels of lactate production compared to hiAstrocytes. In terms of glucose, HFAs have 2.1 times higher consumption levels than hiAstrocytes at 24 h. Still, as we describe their glycogenic phenotype, our study demonstrates the use of hiAstrocytes and flow-based biosensors for metabolic studies of astrocyte function.

  • 7.
    Matthiesen, Isabelle
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Nasiri, Rohollah
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Tamashiro Orrego, Alessandra
    Winkler, Thomas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Metabolic effects from ketone treatment – lactate and glucose turnover in astrocytesManuscript (preprint) (Other academic)
  • 8.
    Matthiesen, Isabelle
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Voulgaris, Dimitrios
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Nikolakopoulou, Polyxeni
    AIMES, Center for Integrated Medical and Engineering Sciences Department of Neuroscience Karolinska Institute Solnavägen 9/B8 Solna 171 65 Sweden.
    Winkler, Thomas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Continuous Monitoring Reveals Protective Effects of N‐Acetylcysteine Amide on an Isogenic Microphysiological Model of the Neurovascular Unit2021In: Small, ISSN 1613-6810, E-ISSN 1613-6829, Vol. 17, no 32, p. 2101785-Article in journal (Refereed)
    Abstract [en]

    Microphysiological systems mimic the in vivo cellular ensemble and microenvironment with the goal of providing more human-like models for biopharmaceutical research. In this study, the first such model of the blood-brain barrier (BBB-on-chip) featuring both isogenic human induced pluripotent stem cell (hiPSC)-derived cells and continuous barrier integrity monitoring with <2 min temporal resolution is reported. Its capabilities are showcased in the first microphysiological study of nitrosative stress and antioxidant prophylaxis. Relying on off-stoichiometry thiol–ene–epoxy (OSTE+) for fabrication greatly facilitates assembly and sensor integration compared to the prevalent polydimethylsiloxane devices. The integrated cell–substrate endothelial resistance monitoring allows for capturing the formation and breakdown of the BBB model, which consists of cocultured hiPSC-derived endothelial-like and astrocyte-like cells. Clear cellular disruption is observed when exposing the BBB-on-chip to the nitrosative stressor linsidomine, and the barrier permeability and barrier-protective effects of the antioxidant N-acetylcysteine amide are reported. Using metabolomic network analysis reveals further drug-induced changes consistent with prior literature regarding, e.g., cysteine and glutathione involvement. A model like this opens new possibilities for drug screening studies and personalized medicine, relying solely on isogenic human-derived cells and providing high-resolution temporal readouts that can help in pharmacodynamic studies.

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  • 9. Poxson, D. J.
    et al.
    Gabrielsson, E. O.
    Bonisoli, A.
    Linderhed, U.
    Abrahamsson, T.
    Matthiesen, Isabelle
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Tybrandt, K.
    Berggren, M.
    Simon, D. T.
    Capillary-Fiber Based Electrophoretic Delivery Device2019In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 11, no 15, p. 14200-14207Article in journal (Refereed)
    Abstract [en]

    Organic electronic ion pumps (OEIPs) are versatile tools for electrophoretic delivery of substances with high spatiotemporal resolution. To date, OEIPs and similar iontronic components have been fabricated using thin-film techniques and often rely on laborious, multistep photolithographic processes. OEIPs have been demonstrated in a variety of in vitro and in vivo settings for controlling biological systems, but the thin-film form factor and limited repertoire of polyelectrolyte materials and device fabrication techniques unnecessarily constrain the possibilities for miniaturization and extremely localized substance delivery, e.g., the greater range of pharmaceutical compounds, on the scale of a single cell. Here, we demonstrate an entirely new OEIP form factor based on capillary fibers that include hyperbranched polyglycerols (dPGs) as the selective electrophoretic membrane. The dPGs enable electrophoretic channels with a high concentration of fixed charges and well-controlled cross-linking and can be realized using a simple "one-pot" fluidic manufacturing protocol. Selective electrophoretic transport of cations and anions of various sizes is demonstrated, including "large" substances that are difficult to transport with other OEIP technologies. We present a method for tailoring and characterizing the electrophoretic channels' fixed charge concentration in the operational state. Subsequently, we compare the experimental performance of these capillary OEIPs to a computational model and explain unexpected features in the ionic current for the transport and delivery of larger, lower-mobility ionic compounds. From this model, we are able to elucidate several operational and design principles relevant to miniaturized electrophoretic drug delivery technologies in general. Overall, the compactness of the capillary OEIP enables electrophoretic delivery devices with probelike geometries, suitable for a variety of ionic compounds, paving the way for less-invasive implantation into biological systems and for healthcare applications.

  • 10.
    Winkler, Thomas
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Feil, Michael
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Stronkman, Eva Francisca Gerhardine Johanna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Matthiesen, Isabelle
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Low-cost microphysiological systems: feasibility study of a tape-based barrier-on-chip for small intestine modeling.2020In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 20, no 7, p. 1212-1226Article in journal (Refereed)
    Abstract [en]

    We see affordability as a key challenge in making organs-on-chips accessible to a wider range of users, particularly outside the highest-resource environments. Here, we present an approach to barrier-on-a-chip fabrication based on double-sided pressure-sensitive adhesive tape and off-the-shelf polycarbonate. Besides a low materials cost, common also to PDMS or thermoplastics, it requires minimal (€100) investment in laboratory equipment, yet at the same time is suitable for upscaling to industrial roll-to-roll manufacture. We evaluate our microphysiological system with an epithelial (Caco-2/BBe1) barrier model of the small intestine, studying the biological effects of permeable support pore size, as well as stimulation with a common food compound (chili pepper-derived capsaicinoids). The cells form tight and continuous barrier layers inside our systems, with comparable permeability but superior epithelial polarization compared to Transwell culture, in line with other perfused microphysiological models. Permeable support pore size is shown to weakly impact barrier layer integrity as well as the metabolic cell profile. Capsaicinoid response proves distinct between culture systems, but we show that impacted metabolic pathways are partly conserved, and that cytoskeletal changes align with previous studies. Overall, our tape-based microphysiological system proves to be a robust and reproducible approach to studying physiological barriers, in spite of its low cost.

  • 11.
    Winkler, Thomas
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Matthiesen, Isabelle
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Voulgaris, Dimitrios
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Nikolakopoulou, P.
    Herland, Anna
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems. AIMES, Department of Neuroscience, Karolinska Institute, Sweden.
    Continuous monitoring of isogenic blood-brain barrier integrity in a pdms-free microphysiological system2020In: MicroTAS 2020 - 24th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Chemical and Biological Microsystems Society , 2020, p. 963-964Conference paper (Refereed)
    Abstract [en]

    We present a microphysiological system (MPS) of the human blood-brain barrier (BBB) that uniquely combines three key advantages - continuous monitoring, PDMS-free fabrication, and cellular relevance - over existing MPS, and we demonstrate BBB formation, breakdown, and rescue. Specifically, we model nitrosative stress - strongly implicated in brain-related disorders from stroke to Alzheimer's - and its prevention using a BBB-permeable antioxidant. This kind of MPS paves the way toward patient-specific BBB modeling for time-resolved studies of drug kinetics and/or side effects towards personalized treatment planning.

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