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  • 1. Abitbol, T.
    et al.
    Ahniyaz, A.
    Álvarez-Asencio, R.
    Fall, A.
    Swerin, Agne
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Surface and Corrosion Science.
    Nanocellulose-Based Hybrid Materials for UV Blocking and Mechanically Robust Barriers2020In: ACS Applied Bio Materials, E-ISSN 2576-6422, Vol. 3, no 4, p. 2245-2254Article in journal (Refereed)
    Abstract [en]

    Nanocellulose (NC)-based hybrid coatings and films containing CeO2 and SiO2 nanoparticles (NPs) to impart UV screening and hardness properties, respectively, were prepared by solvent casting. The NC film-forming component (75 wt % of the overall solids) was composed entirely of cellulose nanocrystals (CNCs) or of CNCs combined with cellulose nanofibrils (CNFs). Zeta potential measurements indicated that the four NP types (CNC, CNF, CeO2, and SiO2) were stably dispersed in water and negatively charged at pH values between 6 and 9. The combination of NPs within this pH range ensured uniform formulations and homogeneous coatings and films, which blocked UV light, the extent of which depended on film thickness and CeO2 NP content, while maintaining good transparency in the visible spectrum (∼80%). The addition of a low amount of CNFs (1%) reduced the film hardness, but this effect was compensated by the addition of SiO2 NPs. Chiral nematic self-assembly was observed in the mixed NC film; however, this ordering was disrupted by the addition of the oxide NPs. The roughness of the hybrid coatings was reduced by the inclusion of oxide NPs into the NC matrix perhaps because the spherical oxide NPs were able to pack into the spaces between cellulose fibrils. We envision these hybrid coatings and films in barrier applications, photovoltaics, cosmetic formulations, such as sunscreens, and for the care and maintenance of wood and glass surfaces, or other surfaces that require a smooth, hard, and transparent finish and protection from UV damage.

  • 2. Asem, H.
    et al.
    Zheng, W.
    Nilsson, Fritjof
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Polymeric Materials.
    Zhang, Y.
    Hedenqvist, Mikael S.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Polymeric Materials.
    Hassan, M.
    Malmström, E.
    Functional Nanocarriers for Drug Delivery by Surface Engineering of Polymeric Nanoparticle Post-Polymerization-Induced Self-Assembly2021In: ACS Applied Bio Materials, E-ISSN 2576-6422, Vol. 4, no 1, p. 1045-1056Article in journal (Refereed)
    Abstract [en]

    Engineered polymeric nanoparticles (NPs) have been comprehensively explored as potential platforms for diagnosis and targeted therapy for several diseases including cancer. Herein, we designed functional poly(acrylic acid)-b-poly(butyl acrylate) (PAA-b-PBA) NPs using reversible addition-fragmentation chain-transfer (RAFT)-mediated emulsion polymerization via polymerization-induced self-assembly (PISA). The hydrophilic PAA-macroRAFT, forming a stabilizing shell (i.e., corona), was chain-extended using the hydrophobic monomer n-butyl acrylate (n-BA), resulting in stable, monodisperse, and reproducible PAA-b-PBA NPs, typically having a diameter of 130 nm. The surface engineering of the PAA-b-PBA NP post-PISA were explored using a two-step approach. The hydrophilic NP-shell corona was modified with allyl groups under mild conditions, using allylamine in water, which resulted in stable allyl-functional NPs (allyl-NPs) suitable for further bioconjugation. The allyl-NPs were subsequently conjugated with a thiol-functional fluorescent dye (BODIPY-SH) to the allyl groups using "thiol-ene"-click chemistry, to mimic the attachment of a thiol-functional target ligand. The successful attachment of BODIPY-SH to the allyl-NPs was corroborated by UV-vis spectroscopy, showing the characteristic absorbance of the BODIPY-fluorophore at 500 nm. Despite modification of NPs with allyl groups and attachment of BODIPY-SH, the NPs retained their colloidal stability and monodispersity as indicated by DLS. This demonstrates that post-PISA functionalization is a robust method for synthesizing functional NPs. Neither the NPs nor allyl-NPs showed significant cytotoxicity toward RAW264.7 or MCF-7 cell lines, which indicates their desirable safety profile. The cellular uptake of the NPs using J774A cells in vitro was found to be time and concentration dependent. The anti-cancer drug doxorubicin was efficiently (90%) encapsulated into the PAA-b-PBA NPs during NP formation. After a small initial burst release during the first 2 h, a controlled release pattern over 7 days was observed. The present investigation demonstrates a potential method for functionalizing polymeric NP post-PISA to produce carriers designed for targeted drug delivery.

  • 3. Carlander, U.
    et al.
    Midander, K.
    Hedberg, Yolanda
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Surface and Corrosion Science.
    Johanson, G.
    Bottai, M.
    Karlsson, H. L.
    Macrophage-Assisted Dissolution of Gold Nanoparticles2019In: ACS Applied Bio Materials, E-ISSN 2576-6422, Vol. 2, no 3, p. 1006-1016Article in journal (Refereed)
    Abstract [en]

    Gold nanoparticles (AuNPs) are readily functionalized and considered biocompatible making them useful in a wide range of applications. Upon human exposure, AuNPs will to a high extent reside in macrophages, cells that are designed to digest foreign materials. To better understand the fate of AuNPs in the human body, their possible dissolution needs to be explored. In this study, we tested the hypothesis that macrophages, and especially stimulated macrophages, can impact the dissolution of AuNPs in a size-dependent manner. We developed an in vitro method to compare the dissolution of citrate coated 5 and 50 nm-sized AuNPs, in terms of released gold ions as measured by inductive coupled mass spectrometry (ICP-MS), in (i) cell medium (alone) (ii) in medium with macrophages present and (iii) in medium with lipopolysaccharide (LPS) triggered macrophages (simulating inflammatory conditions). We found an evident, time-dependent dissolution of AuNPs in cell medium, corresponding to 3% and 0.6% of the added amounts of 5 and 50 nm AuNPs, respectively, after 1 week (168 h) of incubation. The dissolution of 5 nm AuNPs was further increased to 4% in the presence of macrophages and, most strikingly, 14% was dissolved in case of LPS-triggering. In contrast, only a minor increase was observed for 50 nm AuNPs after 1 week in the presence of LPS-triggered macrophages compared to medium alone. Dissolution experiments in the absence of cells highlighted the importance of biomolecules. Our findings thus show dissolution of citrate coated AuNPs that is dependent on size, presence of macrophages, and their inflammatory state. These findings have implications for understanding the transformation/dissolution and fate of AuNPs.

  • 4.
    De Oliveira, Danilo Hirabae
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Biler, Michal
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Theoretical Chemistry and Biology.
    Mim, Carsten
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Structural Biotechnology.
    Nilebäck, Linnea
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Kvick, Mathias
    Spiber Technol AB, SE-11428 Stockholm, Sweden..
    Norman, Patrick
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Theoretical Chemistry and Biology.
    Linares, Mathieu
    Linköping Univ, Lab Organ Elect, SE-58183 Linköping, Sweden.;Linköping Univ, Sci Visualizat Grp, ITN, SE-58183 Linköping, Sweden..
    Hedhammar, My
    KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Silk Assembly against Hydrophobic Surfaces?Modeling and Imaging of Formation of Nanofibrils2023In: ACS Applied Bio Materials, E-ISSN 2576-6422, Vol. 6, no 3, p. 1011-1018Article in journal (Refereed)
    Abstract [en]

    A detailed insight about the molecular organization behind spider silk assembly is valuable for the decoding of the unique properties of silk. The recombinant partial spider silk protein 4RepCT contains four poly-alanine/glycine-rich repeats followed by an amphiphilic C-terminal domain and has shown the capacity to self-assemble into fibrils on hydrophobic surfaces. We herein use molecular dynamic simulations to address the structure of 4RepCT and its different parts on hydrophobic versus hydrophilic surfaces. When 4RepCT is placed in a wing arrangement model and periodically repeated on a hydrophobic surface, fi-sheet structures of the poly-alanine repeats are preserved, while the CT part is settled on top, presenting a fibril with a height of similar to 7 nm and a width of similar to 11 nm. Both atomic force microscopy and cryo-electron microscopy imaging support this model as a possible fibril formation on hydrophobic surfaces. These results contribute to the understanding of silk assembly and alignment mechanism onto hydrophobic surfaces.

  • 5.
    Ghaffarlou, Mohammadreza
    et al.
    Hacettepe Univ, Dept Chem, TR-06800 Ankara, Turkey..
    Ilk, Sedef
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience. Nigde Omer Halisdemir Univ, Fac Med, Dept Immunol, TR-51240 Nigde, Turkey..
    Hammamchi, Hamideh
    Hacettepe Univ, Dept Biol, TR-06800 Ankara, Turkey..
    Kirac, Feyza
    Hacettepe Univ, Dept Chem, TR-06800 Ankara, Turkey..
    Okan, Meltem
    Middle East Tech Univ, Dept Micro & Nanotechnol, TR-06800 Ankara, Turkey..
    Guven, Olgun
    Hacettepe Univ, Dept Chem, TR-06800 Ankara, Turkey..
    Barsbay, Murat
    Hacettepe Univ, Dept Chem, TR-06800 Ankara, Turkey..
    Green and Facile Synthesis of Pullulan-Stabilized Silver and Gold Nanoparticles for the Inhibition of Quorum Sensing2022In: ACS Applied Bio Materials, E-ISSN 2576-6422, Vol. 5, no 2, p. 517-527Article in journal (Refereed)
    Abstract [en]

    Pullulan (Pull) decorated with monodisperse Ag and Au nanoparticles (NPs) was synthesized by a simple and green method. Samples were characterized by FTIR, UV-vis, NMR, XRD, TGA, SEM, XPS, DLS, and TEM. SEM images showed highly oriented microforms reported for the first time for Pull, because of the supramolecular self-assembling behavior of Pull chains. Antimicrobial and quorum sensing (QS) inhibition activities were tested against six pathogen bacteria and reporter and biomonitor strain. Pull decorated with NPs, in particular, Ag-modified ones, outperformed pristine Pull. The cell proliferation was tested with an MTT assay. NPs-decorated Pull was studied for the first time as an inhibitory agent against bacterial signal molecules and found to be a good candidate. The promising performance of AgNPs@Pull compared to the commercial antibiotic gentamicin showed that it has great potential as a therapeutic approach to overcome the bacterial resistance that has developed against conventional antibiotics.

  • 6.
    Kong, Na
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Organic chemistry.
    Park, J.
    Yang, X.
    Ramström, Olof
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Organic chemistry.
    Yan, Mingdi
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Organic chemistry.
    Carbohydrate Functionalization of Few-Layer Graphene through Microwave-Assisted Reaction of Perfluorophenyl Azide2019In: ACS Applied Bio Materials, E-ISSN 2576-6422, Vol. 2, no 1, p. 284-291Article in journal (Refereed)
    Abstract [en]

    The excellent physical and chemical properties of graphene make it an attractive nanomaterial and a component in high-performance nanocomposite materials. To prepare graphene-based nanocomposite materials, chemical functionalization is often necessary. Water-soluble ligands such as carbohydrates not only make the functionalized graphene compatible with aqueous media, but also introduce biorecognition, which is important for graphene to be used in biotechnology. In this study, we report the derivatization of few-layer graphene (FLG) with carbohydrates through microwave-assisted reaction of perfluorophenyl azide (PFPA). FLG was first treated with PFPA under microwave radiation. Subsequent conjugation with glycosyl amine gave carbohydrate-presenting FLG. Thermogravimetric analysis showed that microwave radiation gave a higher degree of functionalization compared to conventional heating, with higher weight losses for both PFPA and Man ligands. The carbohydrates (mannose and galactose) retained their bioactivity, as demonstrated by the lectin binding assays. Higher degree of binding toward lectins was obtained for the carbohydrate-functionalized FLG prepared by microwave radiation than the conventional heating.

  • 7.
    Kopplin, G.
    et al.
    Norwegian Biopolymer Laboratory (NOBIPOL), Department of Biotechnology, NTNU, Trondheim 7491, Norway.
    Rokstad, A. M.
    Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, NTNU, Trondheim 7030, Norway.
    Melida, Hugo
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience.
    Bulone, Vincent
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience.
    Skjåk-Bræk, G.
    Norwegian Biopolymer Laboratory (NOBIPOL), Department of Biotechnology, NTNU, Trondheim 7491, Norway.
    Aachmann, F. L.
    Norwegian Biopolymer Laboratory (NOBIPOL), Department of Biotechnology, NTNU, Trondheim 7491, Norway.
    Structural Characterization of Fucoidan from Laminaria hyperborea: Assessment of Coagulation and Inflammatory Properties and Their Structure-Function Relationship2018In: ACS Applied Bio Materials, E-ISSN 2576-6422, Vol. 1, no 6, p. 1880-1892Article in journal (Refereed)
    Abstract [en]

    The structure of fucoidan isolated from Laminaria hyperborea was elucidatedand chemically tailored in order to obtain a clear structure−function relationship on bioactiveproperties with a minimal amount of variations among the tested molecules. Analysis revealeda sugar composition of 97.8% fucose and 2.2% galactose. Analysis of the glycosidic linkagesshowed (1→3)-α-L-fuco-pyranose (31.9%) to be the dominant residue, followed by 1→2-linked (13.2%) and 1→4-linked (7.7%) fuco-pyranose as well as a high degree of branching(22.4%). Inductively coupled plasma mass spectrometry (ICP-MS) revealed a sulfate contentof 53.8% (degree of sulfation (DS) = 1.7). Raman spectroscopy determined SO4 located axialat 4C and equatorial at 2C as well as an absence of acetylation. SEC-MALS analysisdetermined a high molecular weight (Mw = 469 kDa), suggesting a highly flexible main chainwith short side chains. Both chemical shifts of the fucoidan, proton, and carbon were assignedby NMR and revealed a highly heterogeneous structure in terms of glycosidic linkages.Bioactivity was assessed using a lepirudin-based whole blood model. The immediate responsesby coagulation and complement cascades were measured by prothrombine factor 1 and 2(PTF1.2) and the terminal complement complex (TCC). Cytokines involved in inflammation were detected in a 27-plexcytokine assay. Fucoidan with a high Mw and DS inhibited coagulation, complement, and the cytokines PDGF-BB, RANTES,and IP-10, while activating MCP-1. These effects were obtained at the concentration of 1000 ug/mL and partly at 100 ug/mL.In low concentrations (10 ug/mL), a coagulation stimulating effect of highly sulfated fucoidans (DS = 1.7, Mw = 469 kDa or20.3) was obtained. These data point to a multitude of effects linked to the sulfation degree that needs further mechanisticexploration.

  • 8. Mehandzhiyski, A. Y.
    et al.
    Engel, Emile
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Larsson, Per A.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Fibre- and Polymer Technology, Fibre Technology.
    Re, G. L.
    Zozoulenko, I. V.
    Microscopic Insight into the Structure-Processing-Property Relationships of Core-Shell Structured Dialcohol Cellulose Nanoparticles2022In: ACS Applied Bio Materials, E-ISSN 2576-6422, Vol. 5, no 10, p. 4793-4802Article in journal (Refereed)
    Abstract [en]

    In the quest to develop sustainable and environmentally friendly materials, cellulose is a promising alternative to synthetic polymers. However, native cellulose, in contrast to many synthetic polymers, cannot be melt-processed with traditional techniques because, upon heating, it degrades before it melts. One way to improve the thermoplasticity of cellulose, in the form of cellulose fibers, is through chemical modification, for example, to dialcohol cellulose fibers. To better understand the importance of molecular interactions during melt processing of such modified fibers, we undertook a molecular dynamics study of dialcohol cellulose nanocrystals with different degrees of modification. We investigated the structure of the nanocrystals as well as their interactions with a neighboring nanocrystal during mechanical shearing, Our simulations showed that the stress, interfacial stiffness, hydrogen-bond network, and cellulose conformations during shearing are highly dependent on the degree of modification, water layers between the crystals, and temperature. The melt processing of dialcohol cellulose with different degrees of modification and/or water content in the samples was investigated experimentally by fiber extrusion with water used as a plasticizer. The melt processing was easier when increasing the degree of modification and/or water content in the samples, which was in agreement with the conclusions derived from the molecular modeling. The measured friction between the two crystals after the modification of native cellulose to dialcohol cellulose, in some cases, halved (compared to native cellulose) and is also reduced with increasing temperature. Our results demonstrate that molecular modeling of modified nanocellulose fibers can provide fundamental information on the structure-property relationships of these materials and thus is valuable for the development of new cellulose-based biomaterials.

  • 9. Osella, S.
    et al.
    Knippenberg, Stefan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Theoretical Chemistry and Biology.
    Laurdan as a Molecular Rotor in Biological Environments2019In: ACS Applied Bio Materials, E-ISSN 2576-6422, Vol. 2, no 12, p. 5769-5778Article in journal (Refereed)
    Abstract [en]

    Laurdan is one of the most used fluorescent probes for lipid membrane phase recognition. Despite its wide use for optical techniques and its versatility as a solvatochromic probe, little is known regarding its use as molecular rotor, for which clear evidence is found in the current study. Although recent computational and experimental studies suggest the existence of two stable conformations of laurdan in different membrane phases, it is difficult to experimentally probe their prevalence. By means of multiscale computational approaches, we prove now that this information can be obtained through the optical properties of the two conformers, ranging from one-photon absorption over two-photon absorption to the first hyperpolarizability. Fluorescence decay and anisotropy analyses are performed as well and stress the importance of laurdan's conformational versatility. As a molecular rotor and with reference to the distinct properties of its conformers, laurdan can be used to probe biochemical processes that change the lipid orders in cell membranes.

  • 10.
    Panagiotis Tasiopoulos, Christos
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Technology.
    Petronis, Sarunas
    Sahlin, Herman
    Hedhammar, My
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Technology.
    Surface Functionalization of PTFE Membranes Intended for Guided Bone Regeneration Using Recombinant Spider Silk2020In: ACS Applied Bio Materials, E-ISSN 2576-6422, Vol. 3, no 1, p. 577-583Article in journal (Refereed)
    Abstract [en]

    Alveolar bone loss is usually treated with guided bone regeneration, a dental procedure which utilizes a tissue-separation membrane. The barrier membrane prevents pathogens and epithelial cells to invade the bone augmentation site, thereby permitting osteoblasts to deposit minerals and build up bone. This study aims at adding bioactive properties to otherwise inert PTFE membranes in order to enhance cell adherence and promote proliferation. A prewetting by ethanol and stepwise hydration protocol was herein employed to overcome high surface tension of PTFE membranes and allow for a recombinant spider silk protein, functionalized with a cell-binding motif from fibronectin (FN-silk), to self-assemble into a nanofibrillar coating. HaCaT and U-2 OS cells were seeded onto soft and hard tissue sides, respectively, of membranes coated with FN-silk. The cells could firmly adhere as early as 1 h post seeding, as well as markedly grow in numbers when kept in culture for 7 days. Fluorescence and scanning electron microscopy images revealed that adherent cells could form a confluent monolayer and develop essential cell–cell contacts during 1 week of culture. Hence, functionalized PTFE membranes have a potential of better integration at the implantation site, with reduced risk of membrane displacement as well as exposure to oral pathogens.

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  • 11. Pandurangan, K.
    et al.
    Roy, B.
    Rajasekhar, K.
    Suseela, Y. V.
    Nagendra, P.
    Chaturvedi, A.
    Satwik, U. R.
    Natarajan Arul, Murugan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Theoretical Chemistry and Biology.
    Ramamurty, U.
    Govindaraju, T.
    Molecular Architectonics of Cyclic Dipeptide Amphiphiles and Their Application in Drug Delivery2020In: ACS Applied Bio Materials, E-ISSN 2576-6422, Vol. 3, no 5, p. 3413-3422Article in journal (Refereed)
    Abstract [en]

    Assembly and co-assemblies of peptide amphiphiles through specific noncovalent forces expand the space of molecular architectonics-driven construction of diverse nanoarchitectures with potential biological applications. In this work, cyclic dipeptide amphiphiles (CDPAs) of cyclo(Gly-Asp) with varying lengths of alkyl chains (C8-C18) were synthesized, and their molecular organization was studied. The noncovalent interactions of the components, CDP and alkyl chain, drive the molecular self-assembly of CDPAs into well-defined and diverse nanoarchitectures such as nanotubes, nanospheres, nano/microsheets, and flowers. The co-assembly of CDPAs with biological molecules such as nucleosides was studied to ascertain their utility as potential drug delivery vehicles. Mechanical properties of these nanoarchitectures in nanoindentation study established them as robust in nature. A temperature-dependent NMR study confirmed the formation of stable co-assembly of CDPAs, primarily driven by the intermolecular hydrogen bonding interactions. Computational modeling of oligomers of CDPAs and their co-assembly with nucleosides/nucleotides reveal the molecular level interactions and driving force behind such assemblies. CDPAs exhibit good biocompatibility and cytocompatibility, as revealed by the cellular studies which substantiated their suitability for drug delivery applications. The co-assembly of CDPA with an anticancer drug 5-bromo-2′-deoxyuridine (BrdU) was studied as a drug delivery platform and cytotoxicity was successfully assessed in HeLa cells. Computational modeling of the oligomers of CDPAs and their co-assembly with the drug molecule was performed to understand the molecular level interactions and driving force behind the assemblies. Our findings reveal the design strategy to construct diverse structural architectures using CDP as the modular building unit and specific molecular interactions driven co-assembly for potential application as drug delivery carrier. 

  • 12. Qiao, S.
    et al.
    Zhao, Y.
    Tian, H.
    Manike, I.
    Ma, L.
    Yan, Hongji
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Glycoscience.
    Tian, W.
    3D Co-cultured Endothelial Cells and Monocytes Promoted Cancer Stem Cells' Stemness and Malignancy2021In: ACS Applied Bio Materials, E-ISSN 2576-6422, Vol. 4, no 1, p. 441-450Article in journal (Refereed)
    Abstract [en]

    Cancer stem cells (CSCs) are self-renewing and constitute the primary cause of cancer relapse post-cancer therapy. The CSC niche is composed of various nonmalignant stromal cells that support CSCs' survival during cancer chemoradiotherapy. Understanding the cross-talk between CSCs and stromal cells could pave the way for developing therapeutic strategies to eradicate CSCs. Traditionally, CSC research has been relying on animal models, which can give rise to complications and poor translation in clinical practice. An efficient model to co-culture CSCs and stromal cells is urgently needed. Hence, we leveraged our expertise in enriching CSCs from in vitro cell lines with a 3D alginate-based platform, as reported previously. We established a 3D co-culture system that allowed us to study the interactions between stromal cells and CSCs over an extended period. We showed that the self-renewal capacity and stemness of CSCs were significantly enhanced when co-cultured with 3D cultured human umbilical vein endothelial cells (HUVECs) or a human monocyte cell line (THP1). Strikingly, the expression of MDR1 in 3D co-cultured CSCs was upregulated, leading to enhanced chemotoxic drug tolerance. We suggest that our in vitro co-culture model can impact CSC research and clinical practice when the goal is to develop therapeutics that target and eradicate CSCs by targeting stromal cells. 

  • 13.
    Shafagh, Reza Zandi
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Shen, Joanne X.
    Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden.
    Youhanna, Sonia
    Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden.
    Guo, Weijin
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Lauschke, Volker M.
    Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden.
    van der Wijngaart, Wouter
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Haraldsson, Klas Tommy
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Facile Nanoimprinting of Robust High-Aspect-Ratio Nanostructures for Human Cell Biomechanics2020In: ACS Applied Bio Materials, E-ISSN 2576-6422, Vol. 3, no 12, p. 8757-8767Article in journal (Refereed)
    Abstract [en]

    High-aspect-ratio and hierarchically nanostructured surfaces are common in nature. Synthetic variants are of interest for their specific chemical, mechanic, electric, photonic, or biologic properties but are cumbersome in fabrication or suffer from structural collapse. Here, we replicated and directly biofunctionalized robust, large-area, and high-aspect-ratio nanostructures by nanoimprint lithography of an off-stoichiometric thiol–ene-epoxy polymer. We structured—in a single-step process—dense arrays of pillars with a diameter as low as 100 nm and an aspect ratio of 7.2; holes with a diameter of 70 nm and an aspect ratio of >20; and complex hierarchically layered structures, all with minimal collapse and defectivity. We show that the nanopillar arrays alter mechanosensing of human hepatic cells and provide precise spatial control of cell attachment. We speculate that our results can enable the widespread use of high-aspect-ratio nanotopograhy applications in mechanics, optics, and biomedicine.

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