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  • 1.
    Rasti Boroojeni, Fatemeh
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Naeimipour, Sajjad
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Lifwergren, Philip
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Abrahamsson, Annelie
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Dabrosin, Charlotta
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Proteolytic remodeling of 3D bioprinted tumor microenvironments2024In: Biofabrication, ISSN 1758-5082, E-ISSN 1758-5090, Vol. 16, no 2, article id 025002Article in journal (Refereed)
    Abstract [en]

    In native tissue, remodeling of the pericellular space is essential for cellular activities and is mediated by tightly regulated proteases. Protease activity is dysregulated in many diseases, including many forms of cancer. Increased proteolytic activity is directly linked to tumor invasion into stroma, metastasis, and angiogenesis as well as all other hallmarks of cancer. Here we show a strategy for 3D bioprinting of breast cancer models using well-defined protease degradable hydrogels that can facilitate exploration of the multifaceted roles of proteolytic extracellular matrix remodeling in tumor progression. We designed a set of bicyclo[6.1.0]nonyne functionalized hyaluronan (HA)-based bioinks cross-linked by azide-modified poly(ethylene glycol) (PEG) or matrix metalloproteinase (MMP) degradable azide-functionalized peptides. Bioprinted structures combining PEG and peptide-based hydrogels were proteolytically degraded with spatial selectivity, leaving non-degradable features intact. Bioprinting of tumor-mimicking microenvironments using bioinks comprising human breast cancer cells (MCF-7) and fibroblast in hydrogels with different susceptibilities to proteolytic degradation shows that MCF-7 proliferation and spheroid size were significantly increased in protease degradable hydrogel compartments, but only in the presence of fibroblasts. In the absence of fibroblasts in the stromal compartment, cancer cell proliferation was reduced and did not differ between degradable and nondegradable hydrogels. The interactions between spatially separated fibroblasts and MCF-7 cells consequently resulted in protease-mediated remodeling of the bioprinted structures and a significant increase in cancer cell spheroid size, highlighting the close interplay between cancer cells and stromal cells in the tumor microenvironment and the influence of proteases in tumor progression.

  • 2.
    Eskilsson, Olof
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Kollenchery Ramanathan, Sneha
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Du Rietz, Anna
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Guerrero Florez, Valentina
    Linköping University, Department of Physics, Chemistry and Biology, Nanostructured Materials. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Uvdal, Kajsa
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Björk, Emma
    Linköping University, Department of Physics, Chemistry and Biology, Nanostructured Materials. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Self-Assembly of Metal Nanoparticles in Bacterial Cellulose for the Fabrication of Soft Substrate-Supported Catalysts2024In: ACS Applied Nano Materials, E-ISSN 2574-0970Article in journal (Refereed)
    Abstract [en]

    The transition to green and sustainable catalysts necessitates efficient and safe preparation techniques using abundant and renewable resources. Many metal nanoparticles (NPs) are excellent catalysts but suffer from poor colloidal stability. NP immobilization or fabrication of metal nanostructures on solid supports can avoid issues with NP aggregation and facilitate the reuse of catalysts, but it may result in a decrease in the catalytic performance of the NPs. Here, we show that well-defined colloidal silver, gold, and platinum NPs can be self-assembled in bacterial nanocellulose (BC) membranes, yielding BC-NP nanocomposites that are highly catalytically active using the reduction of 4-nitrophenol (4-NP) as a model reaction. The large effective surface area of BC enables the assembly of large quantities of NPs, resulting in materials with excellent catalytic performance. To address the mass transport limitations of reactants through the 3D nanofibrillar BC network, the membranes were dissociated using sonication to produce dispersed nanocellulose fibrils. This process dramatically reduced the time required for the adsorption of the NPs from days to minutes. Moreover, the catalytic performance of the nanofibril-supported NPs was drastically improved. A turnover frequency above 21,000 h(-1) was demonstrated, which is more than one order of magnitude higher than that for previously reported soft substrate-supported AuNP-based catalytic materials. The ease of fabrication, abundance, and low environmental footprint of the support material, along with reusability, stability, and unprecedented catalytic performance, make BC-NP nanocomposites a compelling option for green and sustainable catalysis.

  • 3.
    Matthiesen, Isabelle
    et al.
    KTH Royal Inst Technol, Sweden; AstraZeneca, Sweden.
    Jury, Michael
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Rasti Boroojeni, Fatemeh
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Ludwig, Saskia L.
    KTH Royal Inst Technol, Sweden.
    Holzreuter, Muriel
    Karolinska Inst, Sweden.
    Buchmann, Sebastian
    KTH Royal Inst Technol, Sweden; Karolinska Inst, Sweden; KTH Royal Inst Technol, Sweden.
    Träger, Andrea
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Winkler, Thomas E.
    KTH Royal Inst Technol, Sweden; Tech Univ Carolo Wilhelmina Braunschweig, Germany; Tech Univ Carolo Wilhelmina Braunschweig, Germany.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Herland, Anna
    KTH Royal Inst Technol, Sweden; Karolinska Inst, Sweden; KTH Royal Inst Technol, 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.

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  • 4.
    Wiman, Emanuel
    et al.
    Örebro University, Sweden.
    Zattarin, Elisa
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Faculty of Science & Engineering. Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering.
    Bengtsson, Torbjörn
    Örebro University, Sweden.
    Selegård, Robert
    Linköping University, Faculty of Science & Engineering. Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering.
    Khalaf, Hazem
    Örebro University, Sweden.
    Development of novel broad-spectrum antimicrobial lipopeptides derived from plantaricin NC8 β2023In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, no 1, article id 4104Article in journal (Refereed)
    Abstract [en]

    Bacterial resistance towards antibiotics is a major global health issue. Very few novel antimicrobial agents and therapies have been made available for clinical use during the past decades, despite an increasing need. Antimicrobial peptides have been intensely studied, many of which have shown great promise in vitro. We have previously demonstrated that the bacteriocin Plantaricin NC8 αβ (PLNC8 αβ) from Lactobacillus plantarum effectively inhibits Staphylococcus spp., and shows little to no cytotoxicity towards human keratinocytes. However, due to its limitations in inhibiting gram-negative species, the aim of the present study was to identify novel antimicrobial peptidomimetic compounds with an enhanced spectrum of activity, derived from the β peptide of PLNC8 αβ. We have rationally designed and synthesized a small library of lipopeptides with significantly improved antimicrobial activity towards both gram-positive and gram-negative bacteria, including the ESKAPE pathogens. The lipopeptides consist of 16 amino acids with a terminal fatty acid chain and assemble into micelles that effectively inhibit and kill bacteria by permeabilizing their cell membranes. They demonstrate low hemolytic activity and liposome model systems further confirm selectivity for bacterial lipid membranes. The combination of lipopeptides with different antibiotics enhanced the effects in a synergistic or additive manner. Our data suggest that the novel lipopeptides are promising as future antimicrobial agents, however additional experiments using relevant animal models are necessary to further validate their in vivo efficacy.

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  • 5.
    Naeimipour, Sajjad
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Rasti Boroojeni, Fatemeh
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Lifwergren, Philip
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Multimodal and dynamic cross-linking of modular thiolated alginate-based bioinks2023In: Materials Today Advances, E-ISSN 2590-0498, Vol. 19, article id 100415Article in journal (Refereed)
    Abstract [en]

    Engineered extracellular matrix-mimicking hydrogels can facilitate 3D cell culture and fabrication of tissue-like constructs and biologically relevant disease models. Processing of cell-laden hydrogels using additive manufacturing techniques further allows for the development of tissue-mimetic structures with higher spatial complexity. Whereas a wide range of printable hydrogels is available, they tend to lack biological functionality and cell compatibility. Here we show an enzymatically mediated thiol-based cross-linking strategy for the design of modular and cytocompatible hydrogel-based bioinks for 3D bioprinting of dynamic multi-material architectures. Alginate is functionalized with cysteines modified with an enzyme-labile thiol protection group. Deprotection using penicillin G acylase (PGA) generates free thiols on-demand, enabling hydrogel cross-linking using thiol-reactive cross-linkers and intermolecular disulfides while avoiding undesired and uncontrolled thiol oxidation. Remaining free thiols can be used for post-printing hydrogel functionalization and lamination of multilayer structures. Moreover, the addition of PGA to a thermo-reversible hydrogel support bath enables the bioprinting of cell-laden 3D structures with high cell viability and excellent shape fidelity. The possibilities to enzymatically generate free thiols during bioprinting facilitate cross-linking and tuning of bioink properties using cytocompatible chemistries and allow for the printing of complex and dynamic cell-laden structures.

  • 6.
    Eskilson, Olof
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Zattarin, Elisa
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Berglund, Linn
    Division of Materials Science, Department of Engineering Sciences and Mathematics, Luleå University of Technology, Luleå, Sweden.
    Oksman, Kristiina
    Division of Materials Science, Department of Engineering Sciences and Mathematics, Luleå University of Technology, Luleå, Sweden.
    Hanna, Kristina
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Rakar, Jonathan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Sivlér, Petter
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Skog, Mårten
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Rinklake, Ivana
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Shamasha, Rozalin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Sotra, Zeljana
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Starkenberg, Annika
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Odén, Magnus
    Linköping University, Department of Physics, Chemistry and Biology, Nanostructured Materials. Linköping University, Faculty of Science & Engineering.
    Wiman, Emanuel
    Cardiovascular Research Centre, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Khalaf, Hazem
    Cardiovascular Research Centre, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Bengtsson, Torbjörn
    Cardiovascular Research Centre, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Junker, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Björk, Emma
    Linköping University, Department of Physics, Chemistry and Biology, Nanostructured Materials. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Nanocellulose composite wound dressings for real-time pH wound monitoring2023In: Materials Today Bio, ISSN 2590-0064, Vol. 19, article id 100574Article in journal (Refereed)
    Abstract [en]

    The skin is the largest organ of the human body. Wounds disrupt the functions of the skin and can have catastrophic consequences for an individual resulting in significant morbidity and mortality. Wound infections are common and can substantially delay healing and can result in non-healing wounds and sepsis. Early diagnosis and treatment of infection reduce risk of complications and support wound healing. Methods for monitoring of wound pH can facilitate early detection of infection. Here we show a novel strategy for integrating pH sensing capabilities in state-of-the-art hydrogel-based wound dressings fabricated from bacterial nanocellulose (BC). A high surface area material was developed by self-assembly of mesoporous silica nanoparticles (MSNs) in BC. By encapsulating a pH-responsive dye in the MSNs, wound dressings for continuous pH sensing with spatiotemporal resolution were developed. The pH responsive BC-based nanocomposites demonstrated excellent wound dressing properties, with respect to conformability, mechanical properties, and water vapor transmission rate. In addition to facilitating rapid colorimetric assessment of wound pH, this strategy for generating functional BC-MSN nanocomposites can be further be adapted for encapsulation and release of bioactive compounds for treatment of hard-to-heal wounds, enabling development of novel wound care materials.

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  • 7.
    Träger, Andrea
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Naeimipour, Sajjad
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Jury, Michael
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Nanocellulose Reinforced Hyaluronan-Based Bioinks2023In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 24, no 7, p. 3086-3093Article in journal (Refereed)
    Abstract [en]

    Bioprinting of hydrogel-based bioinks can allow for thefabricationof elaborate, cell-laden 3D structures. In addition to providing anadequate extracellular matrix mimetic environment and high cell viability,the hydrogels must offer facile extrusion through the printing nozzleand retain the shape of the printed structure. We demonstrate a strategyto incorporate cellulose oxalate nanofibrils in hyaluronan-based hydrogelsto generate shear thinning bioinks that allowed for printing of free-standingmultilayer structures, covalently cross-linked after bioprinting,yielding long-term stability. The storage modulus of the hydrogelswas tunable between 0.5 and 1.5 kPa. The nanocellulose containinghydrogels showed good biocompatibility, with viability of primaryhuman dermal fibroblasts above 80% at day 7 after seeding. The cellswere also shown to tolerate the printing process well, with viabilityabove 80% 24 h after printing. We anticipate that this hydrogel systemcan find broad use as a bioink to produce complex geometries thatcan support cell growth.

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  • 8.
    Baş, Yağmur
    et al.
    Division of Materials Science, Luleå University of Technology, Sweden.
    Berglund, Linn
    Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden..
    Niittylä, Totte
    Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden..
    Zattarin, Elisa
    Linköping University, Faculty of Science & Engineering. Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering.
    Aili, Daniel
    Linköping University, Faculty of Science & Engineering. Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering.
    Sotra, Zeljana
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Rinklake, Ivana
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Junker, Johan
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Rakar, Jonathan
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Oksman, Kristiina
    Division of Materials Science, Luleå University of Technology, Sweden ; Department of Mechanical & Industrial Engineering (MIE), University of Toronto, Ontario, Canada.
    Preparation and Characterization of Softwood and Hardwood Nanofibril Hydrogels: Toward Wound Dressing Applications.2023In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 24, no 12, p. 5605-5619Article in journal (Refereed)
    Abstract [en]

    Hydrogels of cellulose nanofibrils (CNFs) are promising wound dressing candidates due to their biocompatibility, high water absorption, and transparency. Herein, two different commercially available wood species, softwood and hardwood, were subjected to TEMPO-mediated oxidation to proceed with delignification and oxidation in a one-pot process, and thereafter, nanofibrils were isolated using a high-pressure microfluidizer. Furthermore, transparent nanofibril hydrogel networks were prepared by vacuum filtration. Nanofibril properties and network performance correlated with oxidation were investigated and compared with commercially available TEMPO-oxidized pulp nanofibrils and their networks. Softwood nanofibril hydrogel networks exhibited the best mechanical properties, and in vitro toxicological risk assessment showed no detrimental effect for any of the studied hydrogels on human fibroblast or keratinocyte cells. This study demonstrates a straightforward processing route for direct oxidation of different wood species to obtain nanofibril hydrogels for potential use as wound dressings, with softwood having the most potential.

  • 9.
    Arja, Katriann
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Paloncyova, Marketa
    KTH Royal Inst Technol, Sweden; Palacky Univ Olomouc, Czech Republic.
    Linares, Mathieu
    Linköping University, Department of Science and Technology, Laboratory of Organic Electronics. Linköping University, Faculty of Science & Engineering.
    Lindgren, Mikael
    Norwegian Univ Sci & Technol, Norway.
    Norman, Patrick
    KTH Royal Inst Technol, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Self-Assembly of Chiro-Optical Materials from Nonchiral Oligothiophene-Porphyrin Derivatives and Random Coil Synthetic Peptides2023In: ChemPlusChem, E-ISSN 2192-6506, Vol. 88, no 1Article in journal (Refereed)
    Abstract [en]

    Biomimetic chiral optoelectronic materials can be utilized in electronic devices, biosensors and artificial enzymes. Herein, this work reports the chiro-optical properties and architectural arrangement of optoelectronic materials generated from self-assembly of initially nonchiral oligothiophene-porphyrin derivatives and random coil synthetic peptides. The photo-physical- and structural properties of the materials were assessed by absorption-, fluorescence- and circular dichroism spectroscopy, as well as dynamic light scattering, scanning electron microscopy and theoretical calculations. The materials display a three-dimensional ordered helical structure and optical activity that are observed due to an induced chirality of the optoelectronic element upon interaction with the peptide. Both these properties are influenced by the chemical composition of the oligothiophene-porphyrin derivative, as well as the peptide sequence. We foresee that our findings will aid in developing self-assembled optoelectronic materials with dynamic architectonical accuracies, as well as offer the possibility to generate the next generation of materials for a variety of bioelectronic applications.

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  • 10.
    Berglund, Linn
    et al.
    Luleå University of Technology, Sweden.
    Squinca, Paula
    Luleå University of Technology, Sweden; Embrapa Instrumentation, Brazil.
    Baş, Yağmur
    Luleå University of Technology, Sweden.
    Zattarin, Elisa
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Faculty of Science & Engineering. Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering.
    Rakar, Jonathan
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Junker, Johan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Starkenberg, Annika
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Region Östergötland, Regionledningskontoret, Center for Disaster Medicine and Traumatology.
    Diamanti, Mattia
    Luleå University of Technology, Sweden.
    Sivlér, Petter
    S2Medical AB, Sweden.
    Skog, Mårten
    S2Medical AB, Sweden.
    Oksman, Kristiina
    Luleå University of Technology, Sweden.
    Self-Assembly of Nanocellulose Hydrogels Mimicking Bacterial Cellulose for Wound Dressing Applications2023In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 24, no 5, p. 2264-2277Article in journal (Refereed)
    Abstract [en]

    The self-assembly of nanocellulose in the form of cellulose nanofibers (CNFs) can be accomplished via hydrogen-bonding assistance into completely bio-based hydrogels. This study aimed to use the intrinsic properties of CNFs, such as their ability to form strong networks and high absorption capacity and exploit them in the sustainable development of effective wound dressing materials. First, TEMPO-oxidized CNFs were separated directly from wood (W-CNFs) and compared with CNFs separated from wood pulp (P-CNFs). Second, two approaches were evaluated for hydrogel self-assembly from W-CNFs, where water was removed from the suspensions via evaporation through suspension casting (SC) or vacuum-assisted filtration (VF). Third, the W-CNF-VF hydrogel was compared to commercial bacterial cellulose (BC). The study demonstrates that the self-assembly via VF of nanocellulose hydrogels from wood was the most promising material as wound dressing and displayed comparable properties to that of BC and strength to that of soft tissue.

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  • 11.
    Jury, Michael
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Matthiesen, Isabelle
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Boroojeni, Fatemeh Rasti
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Ludwig, Saskia L.
    KTH Royal Institute of Technology, Stockholm, Sweden.
    Civitelli, Livia
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering. University of Oxford, England.
    Winkler, Thomas E.
    KTH Royal Institute of Technology, Stockholm, Sweden; Institute of Microtechnology, Center of Pharmaceutical Engineering, Technische Universität Braunschweig, Braunschweig, Germany.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Herland, Anna
    Division of Micro and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden; Department of Neuroscience, Karolinska Institute, Solna, Sweden; Division of Nanobiotechnology, Department of Protein Science, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    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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  • 12.
    Guell-Grau, Pau
    et al.
    Inst Microelect Barcelona IMBCNM CSIC, Spain; CSIC, Spain; BIST, Spain; Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Spain.
    Pi, Francesc
    Univ Autonoma Barcelona, Spain.
    Villa, Rosa
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering. Inst Microelect Barcelona IMBCNM CSIC, Spain; Networking Res Ctr Bioengn Biomat & Nanomed CIBER, Spain.
    Eskilson, Olof
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Nogues, Josep
    CSIC, Spain; BIST, Spain; ICREA, Spain.
    Sepulveda, Borja
    Inst Microelect Barcelona IMBCNM CSIC, Spain.
    Alvarez, Mar
    Inst Microelect Barcelona IMBCNM CSIC, Spain.
    Elastic Plasmonic-Enhanced Fabry-Perot Cavities with Ultrasensitive Stretching Tunability2022In: Advanced Materials, ISSN 0935-9648, E-ISSN 1521-4095, Vol. 34, no 7, article id 2106731Article in journal (Refereed)
    Abstract [en]

    The emerging stretchable photonics field faces challenges, like the robust integration of optical elements into elastic matrices or the generation of large optomechanical effects. Here, the first stretchable plasmonic-enhanced and wrinkled Fabry-Perot (FP) cavities are demonstrated, which are composed of self-embedded arrays of Au nanostructures at controlled depths into elastomer films. The novel self-embedding process is triggered by the Au nanostructures catalytic activity, which locally increases the polymer curing rate, thereby inducing a mechanical stress that simultaneously pulls the Au nanostructures into the polymer and forms a wrinkled skin layer. This geometry yields unprecedented optomechanical effects produced by the coupling of the broad plasmonic modes of the Au nanostructures and the FP modes, which are modulated by the wrinkled optical cavity. As a result, film stretching induces drastic changes in both the spectral position and intensity of the plasmonic-enhanced FP resonances due to the simultaneous cavity thickness reduction and cavity wrinkle flattening, thus increasing the cavity finesse. These optomechanical effects are exploited to demonstrate new strain-sensing approaches, achieving a strain detection limit of 0.006%, i.e., 16-fold lower than current optical strain-detection schemes.

  • 13.
    Naeimipour, Sajjad
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Rasti Boroojeni, Fatemeh
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Enzymatically Triggered Deprotection and Cross-Linking of Thiolated Alginate-Based Bioinks2022In: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 34, no 21, p. 9536-9545Article in journal (Refereed)
    Abstract [en]

    Thiolated polymers are widely used in hydrogels for drug delivery, tissue engineering, and biofabrication. The oxidation of thiols is spontaneous, resulting in the formation of disulfide bridges and cross linking of polymers. The cross-linking process is, however, difficult to control and is initiated directly when the thiolated components are exposed to ambient conditions, which significantly complicates handling of the materials. Here, we show a fully bioorthogonal enzyme-mediated thiol-based chemistry for dynamic covalent cross-linking of carbohydrate-based hydrogels that circumvents the problems with uncontrolled thiol oxidation. Alginate was modified with cysteine residues, protected by an enzyme-labile thiol-protecting group (Phacm). Releasing the Phacm group by penicillin G acylase generates free thiols that oxidize under physiological conditions, resulting in a reversible cross-linking and formation of hydrogels with tunable stiffness. Prior to deprotection, the components can be exposed to ambient conditions. The enzyme-triggered deprotection and subsequent gelation allows for encapsulation of cells and 3D bioprinting of cell-laden hydrogel structures. Remaining deprotected thiols enabled postprinting modifications and hydrogel self-healing. The proposed hydrogel synthesis strategy significantly increases the versatility of thiol-based cross-linking chemistries and provides new possibilities to generate dynamic covalent hydrogels for a broad range of biomedical applications.

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  • 14.
    Sengupta, Anirban
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Azharuddin, Mohammad
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Cardona Gomez, Maria Eugenia
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Devito, Claudia
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    von Castelmur, Eleonore
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Wehlin, Anna
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Pietras, Zuzanna
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Sunnerhagen, Maria
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Alamer, Ali
    King Abdulaziz City Sci & Technol KACST, Saudi Arabia.
    Hinkula, Jorma
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Al-Otaibi, Noha
    King Abdulaziz City Sci & Technol KACST, Saudi Arabia.
    Intranasal Coronavirus SARS-CoV-2 Immunization with Lipid Adjuvants Provides Systemic and Mucosal Immune Response against SARS-CoV-2 S1 Spike and Nucleocapsid Protein2022In: Vaccines, E-ISSN 2076-393X, Vol. 10, no 4, article id 504Article in journal (Refereed)
    Abstract [en]

    In this preclinical two-dose mucosal immunization study, using a combination of S1 spike and nucleocapsid proteins with cationic (N3)/or anionic (L3) lipids were investigated using an intranasal delivery route. The study showed that nasal administration of low amounts of antigens/adjuvants induced a primary and secondary immune response in systemic IgG, mIL-5, and IFN-gamma secreting T lymphocytes, as well as humoral IgA in nasal and intestinal mucosal compartments. It is believed that recipients will benefit from receiving a combination of viral antigens in promoting a border immune response against present and evolving contagious viruses. Lipid adjuvants demonstrated an enhanced response in the vaccine effect. This was seen in the significant immunogenicity effect when using the cationic lipid N3. Unlike L3, which showed a recognizable effect when administrated at a slightly higher concentration. Moreover, the findings of the study proved the efficiency of an intranasally mucosal immunization strategy, which can be less painful and more effective in enhancing the respiratory tract immunity against respiratory infectious diseases.

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  • 15.
    Tran, Thuy
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Martinsson, Erik
    ArgusEye AB, S-58336 Linkoping, Sweden.
    Vargas, Sergio
    Wolfram MathCore AB, S-58330 Linkoping, Sweden.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology, Sensor and Actuator Systems. Linköping University, Faculty of Science & Engineering.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Nanoplasmonic Avidity-Based Detection and Quantification of IgG Aggregates2022In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 94, no 45, p. 15754-15762Article in journal (Refereed)
    Abstract [en]

    Production of therapeutic monoclonal antibodies (mAbs) is a complex process that requires extensive analytical and bioanalytical characterization to ensure high and consistent product quality. Aggregation of mAbs is common and very problematic and can result in products with altered pharmacodynamics and pharmacokinetics and potentially increased immunogenicity. Rapid detection of aggregates, however, remains very challenging using existing analytical techniques. Here, we show a real-time and label-free fiber optical nanoplasmonic biosensor system for specific detection and quantification of immunoglobulin G (IgG) aggregates exploiting Protein A mediated avidity effects. Compared to monomers, IgG aggregates were found to have substantially higher apparent affinity when binding to Protein Afunctionalized sensor chips in a specific pH range (pH 3.8-4.0). Under these conditions, aggregates and monomers showed significantly different binding and dissociation kinetics. Reliable and rapid aggregate quantification was demonstrated with a limit of detection (LOD) and limit of quantification (LOQ) of about 9 and 30 mu g/mL, respectively. Using neural network-based curve fitting, it was further possible to simultaneously quantify monomers and aggregates for aggregate concentrations lower than 30 mu g/mL. Our work demonstrates a unique avidity-based biosensor approach for fast aggregate analysis that can be used for rapid at-line quality control, including lot/batch release testing. This technology can also likely be further optimized for real-time in-line monitoring of product titers and quality, facilitating process intensification and automation.

  • 16.
    Utterström, Johanna
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Barriga, Hanna M. G.
    Karolinska Inst, Sweden.
    Holme, Margaret N.
    Karolinska Inst, Sweden.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Stevens, Molly M.
    Karolinska Inst, Sweden; Imperial Coll London, England; Imperial Coll London, England.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Peptide-Folding Triggered Phase Separation and Lipid Membrane Destabilization in Cholesterol-Rich Lipid Vesicles2022In: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 33, no 4, p. 736-746Article in journal (Refereed)
    Abstract [en]

    Liposome-based drug delivery systems are widely used to improve drug pharmacokinetics but can suffer from slow and unspecific release of encapsulated drugs. Membrane-active peptides, based on sequences derived or inspired from antimicrobial peptides (AMPs), could offer means to trigger and control the release. Cholesterol is used in most liposomal drug delivery systems (DDS) to improve the stability of the formulation, but the activity of AMPs on cholesterol-rich membranes tends to be very low, complicating peptide-triggered release strategies. Here, we show a de novo designed AMP-mimetic peptide that efficiently triggers content release from cholesterol-containing lipid vesicles when covalently conjugated to headgroup-functionalized lipids. Binding to vesicles induces peptide folding and triggers a lipid phase separation, which in the presence of cholesterol results in high local peptide concentrations at the lipid bilayer surface and rapid content release. We anticipate that these results will facilitate the development of peptide-based strategies for controlling and triggering drug release from liposomal drug delivery systems.

  • 17.
    Omer, Abubakr A. M.
    et al.
    Orebro Univ, Sweden.
    Hinkula, Jorma
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology. Linköping University, Faculty of Medicine and Health Sciences.
    Pham-Tue-Hung, Tran
    Orebro Univ, Sweden.
    Melik, Wessam
    Orebro Univ, Sweden.
    Zattarin, Elisa
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Bengtsson, Torbjorn
    Orebro Univ, Sweden.
    Khalaf, Hazem
    Orebro Univ, Sweden.
    Plantaricin NC8 alpha beta rapidly and efficiently inhibits flaviviruses and SARS-CoV-2 by disrupting their envelopes2022In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 11, article id e0278419Article in journal (Refereed)
    Abstract [en]

    Potent broad-spectrum antiviral agents are urgently needed to combat existing and emerging viral infections. This is particularly important considering that vaccine development is a costly and time consuming process and that viruses constantly mutate and render the vaccine ineffective. Antimicrobial peptides (AMP), such as bacteriocins, are attractive candidates as antiviral agents against enveloped viruses. One of these bacteriocins is PLNC8 alpha beta, which consists of amphipathic peptides with positive net charges that display high affinity for negatively charged pathogen membrane structures, including phosphatidylserine rich lipid membranes of viral envelopes. Due to the morphological and physiological differences between viral envelopes and host cell plasma membranes, PLNC8 alpha beta is thought to have high safety profile by specifically targeting viral envelopes without effecting host cell membranes. In this study, we have tested the antiviral effects of PLNC8 alpha beta against the flaviviruses Langat and Kunjin, coronavirus SARS-CoV-2, influenza A virus (IAV), and human immunodeficiency virus-1 (HIV-1). The concentration of PLNC8 alpha beta that is required to eliminate all the infective virus particles is in the range of nanomolar (nM) to micromolar (mu M), which is surprisingly efficient considering the high content of cholesterol (8-35%) in their lipid envelopes. We found that viruses replicating in the endoplasmic reticulum (ER)/Golgi complex, e.g. SARS-CoV-2 and flaviviruses, are considerably more susceptible to PLNC8 alpha beta, compared to viruses that acquire their lipid envelope from the plasma membrane, such as IAV and HIV-1. Development of novel broad-spectrum antiviral agents can significantly benefit human health by rapidly and efficiently eliminating infectious virions and thereby limit virus dissemination and spreading between individuals. PLNC8 alpha beta can potentially be developed into an effective and safe antiviral agent that targets the lipid compartments of viral envelopes of extracellular virions, more or less independent of virus antigenic mutations, which faces many antiviral drugs and vaccines.

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  • 18.
    Tran, Thuy
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Martinsson, Erik
    ArgusEye AB, Spannmalsgatan 55, S-58336 Linkoping, Sweden.
    Gustavsson, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Tronarp, Otto
    Wolfram MathCore AB, Teknikringen 1E, S-58330 Linkoping, Sweden.
    Nilsson, Mats
    BioInvent Int AB, Sweden.
    Hansson, Kristoffer Rudenholm
    BioInvent Int AB, Sweden.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology, Sensor and Actuator Systems. Linköping University, Faculty of Science & Engineering.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Process integrated biosensors for real-time monitoring of antibodies for automated affinity purification2022In: Analytical Methods, ISSN 1759-9660, E-ISSN 1759-9679, Vol. 14, no 44, p. 4555-4562Article in journal (Refereed)
    Abstract [en]

    Therapeutic monoclonal antibodies (mAbs) provide new means for treatments of a wide range of diseases and comprise a large fraction of all new approved drugs. Production of mAbs is expensive compared to conventional drug production, primarily due to the complex processes involved. The affinity purification step is dominating the cost of goods in mAb manufacturing. Process intensification and automation could reduce costs, but the lack of real-time process analytical technologies (PAT) complicates this development. We show a specific and robust fiber optical localized surface plasmon resonance (LSPR) sensor technology that is optimized for in-line product detection in the effluent in affinity capture steps. The sensor system comprises a flow cell and a replaceable sensor chip functionalized with biorecognition elements for specific analyte detection. The high selectivity of the sensor enable detection of mAbs in complex sample matrices at concentrations below 2.5 mu g mL(-1). In place regeneration of the sensor chips allowed for continuous monitoring of multiple consecutive chromatographic separation cycles. Excellent performance was obtained at different purification scales with flow rates up to 200 mL min(-1). This sensor technology facilitates efficient column loading, optimization, and control of chromatography systems, which can pave the way for continuous operation and automation of protein purification steps.

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  • 19.
    Utterström, Johanna
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Naeimipour, Sajjad
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Coiled coil-based therapeutics and drug delivery systems2021In: Advanced Drug Delivery Reviews, ISSN 0169-409X, E-ISSN 1872-8294, Vol. 170, p. 26-43Article, review/survey (Refereed)
    Abstract [en]

    Coiled coils are characterized by an arrangement of two or more alpha-helices into a superhelix and one of few protein motifs where the sequence-to-structure relationship to a large extent have been decoded and understood. The abundance of both natural and de novo designed coil coils provides a rich molecular toolbox for self assembly of elaborate bespoke molecular architectures, nanostructures, and materials. Leveraging on the numerous possibilities to tune both affinities and preferences for polypeptide oligomerization, coiled coils offer unique possibilities to design modular and dynamic assemblies that can respond in a predictable manner to biomolecular interactions and subtle physicochemical cues. In this review, strategies to use coiled coils in design of novel therapeutics and advanced drug delivery systems are discussed. The applications of coiled coils for generating drug carriers and vaccines, and various aspects of using coiled coils for controlling and triggering drug release, and for improving drug targeting and drug uptake are described. The plethora of innovative coiled coil-based molecular systems provide new knowledge and techniques for improving efficacy of existing drugs and can facilitate development of novel therapeutic strategies. (c) 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). 1. Introduction 27 2. The coiled coil motif 27 3. Coiled coils and coiled coil-hybrids for drug delivery and therapeutics 30 3.1. Coiled coils in liposome drug delivery systems 30 3.2. Lipidated coiled coils for assembly of virus-like particles 31 3.3. Coiled coil nanoparticles 31 3.4. Coiled coil nanocarriers 33 3.5. Coiled coil polymer-hybrids 33 3.6. Coiled coil-based hydrogels 36 3.7. Coiled coil inorganic nanoparticle hybrids 37 3.8. Coiled coils combined with cell penetrating peptides 37 3.9. Coiled coils for improved targeting 38

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  • 20.
    Ali, Hala R.
    et al.
    Agr Res Ctr ARC, Egypt.
    Selim, Salah A.
    Cairo Univ, Egypt.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Effects of macrophage polarization on gold nanoparticle-assisted plasmonic photothermal therapy2021In: RSC Advances, E-ISSN 2046-2069, Vol. 11, no 40, p. 25047-25056Article in journal (Refereed)
    Abstract [en]

    Tumor associated macrophages (TAM) are key pathogenic factors in neoplastic diseases. They are known to have plasticity and can polarize into two opposing phenotypes, including the tumoricidal M1 and the protumoral M2 phenotypes with high prevalence of M2-phentoypes in patients with poor prognosis. Strategies for targeting M2-TAM may consequently increase the efficacy of therapeutic strategies for cancer treatment. Gold nanorod-assisted plasmonic photothermal therapy (PPTT) has emerged as a promising treatment for cancer but the effects of macrophage polarization parameters in the performance of this new treatment modality is still unknown. Herein, human monocytic THP-1 cells were polarized into two opposite phenotypic macrophages (M1-TAM and M2-TAM) and their response to PPTT was examined. M2-TAM exhibits a three-fold increase in AuNP uptake compared to M1-TAM. Laser irradiation results in selective killing of pro-tumoral M2-TAM after treatment with AuNPs with limited effects on anti-tumoral M1-TAM. A positive correlation between the expression of CD206 marker and the AuNP uptake may indicate the role of CD206 in facilitating AuNP uptake. Our findings also suggest that the differences in AuNP avidity and uptake between the M1-TAM and M2-TAM phenotypes may be the rationale behind the effectiveness of PPTT in the treatment of solid tumors.

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  • 21.
    Musa, Amani
    et al.
    Orebro Univ, Sweden.
    Wiman, Emanuel
    Orebro Univ, Sweden.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Bengtsson, Torbjörn
    Orebro Univ, Sweden.
    Khalaf, Hazem
    Orebro Univ, Sweden.
    Plantaricin NC8 alpha beta prevents Staphylococcus aureus-mediated cytotoxicity and inflammatory responses of human keratinocytes2021In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 12514Article in journal (Refereed)
    Abstract [en]

    Multidrug resistance bacteria constitue an increasing global health problem and the development of novel therapeutic strategies to face this challenge is urgent. Antimicrobial peptides have been proven as potent agents against pathogenic bacteria shown by promising in vitro results. The aim of this study was to characterize the antimicrobial effects of PLNC8 alpha beta on cell signaling pathways and inflammatory responses of human keratinocytes infected with S. aureus. PLNC8 alpha beta did not affect the viability of human keratinocytes but upregulated several cytokines (IL-1 beta, IL-6, CXCL8), MMPs (MMP1, MMP2, MMP9, MMP10) and growth factors (VEGF and PDGF-AA), which are essential in cell regeneration. S. aureus induced the expression of several inflammatory mediators at the gene and protein level and PLNC8 alpha beta was able to significantly suppress these effects. Intracellular signaling events involved primarily c-Jun via JNK, c-Fos and NF kappa B, suggesting their essential role in the initiation of inflammatory responses in human keratinocytes. PLNC8 alpha beta was shown to modulate early keratinocyte responses, without affecting their viability. The peptides have high selectivity towards S. aureus and were efficient at eliminating the bacteria and counteracting their inflammatory and cytotoxic effects, alone and in combination with low concentrations of gentamicin. We propose that PLNC8 alpha beta may be developed to combat infections caused by Staphylococcus spp.

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  • 22.
    Bengtsson, Torbjörn
    et al.
    Örebro University, Sweden.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering. Örebro University, Sweden.
    Musa, Amani
    Örebro University, Sweden.
    Hultenby, Kjell
    Karolinska Institutet, Sweden.
    Utterström, Johanna
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Sivlér, Petter
    S2Medical AB, 58273, Linköping, Sweden.
    Skog, Mårten
    S2Medical AB, 58273, Linköping, Sweden.
    Nayeri, Fariba
    Department of Infection Control, PEAS Research Institute, Linköping, Sweden.
    Hellmark, Bengt
    Department of Clinical Microbiology, Örebro University Hospital, Sweden.
    Söderquist, Bo
    Cardiovascular Research Centre, School of Medical Sciences, Örebro University, 70362, Örebro, Sweden; Department of Clinical Microbiology, Örebro University Hospital, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Khalaf, Hazem
    Cardiovascular Research Centre, School of Medical Sciences, Örebro University, Sweden.
    Author Correction: Plantaricin NC8 aß exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1Article in journal (Other academic)
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  • 23.
    Aronsson, Christopher
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Jury, Michael
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Naeimipour, Sajjad
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Rasti Boroojeni, Fatemeh
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Christoffersson, Jonas
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering. Univ Skovde, Sweden.
    Lifwergren, Philip
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Dynamic peptide-folding mediated biofunctionalization and modulation of hydrogels for 4D bioprinting2020In: Biofabrication, ISSN 1758-5082, E-ISSN 1758-5090, Vol. 12, no 3, article id 035031Article in journal (Refereed)
    Abstract [en]

    Hydrogels are used in a wide range of biomedical applications, including three-dimensional (3D) cell culture, cell therapy and bioprinting. To enable processing using advanced additive fabrication techniques and to mimic the dynamic nature of the extracellular matrix (ECM), the properties of the hydrogels must be possible to tailor and change over time with high precision. The design of hydrogels that are both structurally and functionally dynamic, while providing necessary mechanical support is challenging using conventional synthesis techniques. Here, we show a modular and 3D printable hydrogel system that combines a robust but tunable covalent bioorthogonal cross-linking strategy with specific peptide-folding mediated interactions for dynamic modulation of cross-linking and functionalization. The hyaluronan-based hydrogels were covalently cross-linked by strain-promoted alkyne-azide cycloaddition using multi-arm poly(ethylene glycol). In addition, ade novodesigned helix-loop-helix peptide was conjugated to the hyaluronan backbone to enable specific peptide-folding modulation of cross-linking density and kinetics, and hydrogel functionality. An array of complementary peptides with different functionalities was developed and used as a toolbox for supramolecular tuning of cell-hydrogel interactions and for controlling enzyme-mediated biomineralization processes. The modular peptide system enabled dynamic modifications of the properties of 3D printed structures, demonstrating a novel route for design of more sophisticated bioinks for four-dimensional bioprinting.

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  • 24.
    Zeng, Shuangshuang
    et al.
    Uppsala Univ, Sweden.
    Li, Shiyu
    Uppsala Univ, Sweden.
    Utterström, Johanna
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Wen, Chenyu
    Uppsala Univ, Sweden.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Zhang, Shi-Li
    Uppsala Univ, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Zhang, Zhen
    Uppsala Univ, Sweden.
    Mechanism and Kinetics of Lipid Bilayer Formation in Solid-State Nanopores2020In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 36, no 6, p. 1446-1453Article in journal (Refereed)
    Abstract [en]

    Solid-state nanopores provide a highly versatile platform for rapid electrical detection and analysis of single molecules. Lipid bilayer coating of the nanopores can reduce nonspecific analyte adsorption to the nanopore sidewalls and increase the sensing selectivity by providing possibilities for tethering specific ligands in a cell-membrane mimicking environment. However, the mechanism and kinetics of lipid bilayer formation from vesicles remain unclear in the presence of nanopores. In this work, we used a silicon-based, truncated pyramidal nanopore array as the support for lipid bilayer formation. Lipid bilayer formation in the nanopores was monitored in real time by the change in ionic current through the nanopores. Statistical analysis revealed that a lipid bilayer is formed from the instantaneous rupture of individual vesicle upon adsorption in the nanopores, differing from the generally agreed mechanism that lipid bilayer forms at a high vesicle surface coverage on a planar support. The dependence of the lipid bilayer formation process on the applied bias, vesicle size, and concentration was systematically studied. In addition, the nonfouling properties of the lipid bilayer coated nanopores were demonstrated during long single-stranded DNA translocation through the nanopore array. The findings indicate that the lipid bilayer formation process can be modulated by introducing nanocavities intentionally on the planar surface to create active sites or changing the vesicle size and concentration.

  • 25.
    Palomar, Quentin
    et al.
    Uppsala Univ, Sweden.
    Xu, XingXing
    Uppsala Univ, Sweden.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Zhang, Zhen
    Uppsala Univ, Sweden.
    Peptide decorated gold nanoparticle/carbon nanotube electrochemical sensor for ultrasensitive detection of matrix metalloproteinase-72020In: Sensors and actuators. B, Chemical, ISSN 0925-4005, E-ISSN 1873-3077, Vol. 325, article id 128789Article in journal (Refereed)
    Abstract [en]

    Matrix Metalloproteinase-7 (MMP-7) is a proteolytic enzyme overexpressed in different pathological conditions, including cancer, infection, and cardiovascular diseases, and is a relevant diagnostic biomarker and potential drug target. Here we demonstrate rapid and selective detection of MMP-7 with a limit-of-detection of 6 pg/mL and a dynamic range from 1 x 10(-2) to 1 x 10(3) ng/mL using a peptide decorated gold nanoparticle/carbon nanotube electrochemical sensor. The sensor could be operated in diluted human serum and synthetic urine, with high specificity towards MMP-7. Moreover, the integration of nanomaterials in the sensing electrode significantly increased the signal-to-background ratio and strongly improved the stability of the sensor when compared to a conventional gold electrode. The simple and cost-effective fabrication and the ease of use make this sensor a very promising protease detection device for diagnostics and drug development.

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  • 26.
    Bengtsson, Torbjorn
    et al.
    Orebro Univ, Sweden.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering. Orebro Univ, Sweden.
    Musa, Amani
    Orebro Univ, Sweden.
    Hultenby, Kjell
    Karolinska Inst, Sweden.
    Utterström, Johanna
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Sivler, Petter
    S2Medical AB, SE-58273 Linkoping, Sweden.
    Skog, Marten
    S2Medical AB, SE-58273 Linkoping, Sweden.
    Nayeri, Fariba
    PEAS Res Inst, Dept Infect Control, SE-58273 Linkoping, Sweden.
    Hellmark, Bengt
    Orebro Univ Hosp, Sweden.
    Soderquist, Bo
    Orebro Univ, Sweden; Orebro Univ Hosp, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Khalaf, Hazem
    Orebro Univ, Sweden.
    Plantaricin NC8 alpha beta exerts potent antimicrobial activity against Staphylococcus spp. and enhances the effects of antibiotics2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 3580Article in journal (Refereed)
    Abstract [en]

    The use of conventional antibiotics has substantial clinical efficacy, however these vital antimicrobial agents are becoming less effective due to the dramatic increase in antibiotic-resistant bacteria. Novel approaches to combat bacterial infections are urgently needed and bacteriocins represent a promising alternative. In this study, the activities of the two-peptide bacteriocin PLNC8 alpha beta were investigated against different Staphylococcus spp. The peptide sequences of PLNC8 alpha and beta were modified, either through truncation or replacement of all L-amino acids with D-amino acids. Both L- and D-PLNC8 alpha beta caused rapid disruption of lipid membrane integrity and were effective against both susceptible and antibiotic resistant strains. The D-enantiomer was stable against proteolytic degradation by trypsin compared to the L-enantiomer. Of the truncated peptides, beta 1-22, beta 7-34 and beta 1-20 retained an inhibitory activity. The peptides diffused rapidly (2min) through the bacterial cell wall and permeabilized the cell membrane, causing swelling with a disorganized peptidoglycan layer. Interestingly, sub-MIC concentrations of PLNC8 alpha beta substantially enhanced the effects of different antibiotics in an additive or synergistic manner. This study shows that PLNC8 alpha beta is active against Staphylococcus spp. and may be developed as adjuvant in combination therapy to potentiate the effects of antibiotics and reduce their overall use.

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  • 27.
    Svärd, Anna
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering. Orebro Univ, Sweden.
    Neilands, Jessica
    Malmo Univ, Sweden.
    Palm, Eleonor
    Orebro Univ, Sweden.
    Svensater, Gunnel
    Malmo Univ, Sweden.
    Bengtsson, Torbjorn
    Orebro Univ, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Protein-Functionalized Gold Nanoparticles as Refractometric Nanoplasmonic Sensors for the Detection of Proteolytic Activity of Porphyromonas gingivalis2020In: ACS Applied Nano Materials, E-ISSN 2574-0970, Vol. 3, no 10, p. 9822-9830Article in journal (Refereed)
    Abstract [en]

    Periodontitis is an inflammatory oral disease that affects a large part of the adult population, causing significant costs and suffering. The key pathogen, Porphyromonas gingivalis, secretes gingipains, which are highly destructive proteases and the most important virulence factors in the pathogenesis of the disease. Currently, periodontitis is diagnosed mainly by mechanical manual probing and radiography, often when the disease has already progressed significantly. The possibilities of detecting gingipain activity in gingival fluid could enable early-stage diagnosis and facilitate treatment. Here, we describe a sensitive nanoparticle-based nanoplasmonic biosensor for the detection of the proteolytic activity of gingipains. Gold nanoparticles (AuNPs) were self-assembled as a submonolayer in multiwell plates and further modified with casein or IgG. The proteolytic degradation of the protein coating was tracked by monitoring the shift in the localized surface plasmon resonance (LSPR) peak position. The sensor performance was investigated using model systems with trypsin and purified gingipains (subtypes Kgp and RgpB) and further validated using supernatants from cultures of P. gingivalis. Proteolytic degradation by proteases in buffer results in a concentration- and time-dependent blueshift of the LSPR band of about 1-2 nm when using casein as a substrate. In bacterial supernatants, the degradation of the protein coating resulted in unspecific binding of proteins present in the complex sample matrix to the nanoparticles, which instead triggered a redshift of about 2 nm of the LSPR band. A significant LSPR shift was seen only in samples with gingipain activity. The sensor showed a limit of detection < 0.1 mu g/mL (4.3 nM), which is well below gingipain concentrations detected in severe chronic periodontitis cases (similar to 50 mu g/mL). This work shows the possibility of developing cost-effective nanoparticle-based biosensors for rapid detection of protease activity for chair-side periodontal diagnostics.

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  • 28.
    Tran, Thuy
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Eskilsson, Olof
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Mayer, Florian
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Gustavsson, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology, Sensor and Actuator Systems. Linköping University, Faculty of Science & Engineering.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Martinsson, Erik
    ArgusEye AB, Spannmalsgatan 55, S-58336 Linkoping, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Real-Time Nanoplasmonic Sensor for IgG Monitoring in Bioproduction2020In: Processes, ISSN 2227-9717, Vol. 8, no 10, article id 1302Article in journal (Refereed)
    Abstract [en]

    Real-time monitoring of product titers during process development and production of biotherapeutics facilitate implementation of quality-by-design principles and enable rapid bioprocess decision and optimization of the production process. Conventional analytical methods are generally performed offline/at-line and, therefore, are not capable of generating real-time data. In this study, a novel fiber optical nanoplasmonic sensor technology was explored for rapid IgG titer measurements. The sensor combines localized surface plasmon resonance transduction and robust single use Protein A-modified sensor chips, housed in a flexible flow cell, for specific IgG detection. The sensor requires small sample volumes (1-150 mu L) and shows a reproducibility and sensitivity comparable to Protein G high performance liquid chromatography-ultraviolet (HPLC-UV). The dynamic range of the sensor system can be tuned by varying the sample volume, which enables quantification of IgG samples ranging from 0.0015 to 10 mg/mL, without need for sample dilution. The sensor shows limited interference from the sample matrix and negligible unspecific protein binding. IgG titers can be rapidly determined in samples from filtered unpurified Chinese hamster ovary (CHO) cell cultures and show good correlation with enzyme-linked immunosorbent assay (ELISA).

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  • 29.
    Eskilson, Olof
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Lindström, Stefan B
    Linköping University, Department of Management and Engineering, Solid Mechanics. Linköping University, Faculty of Science & Engineering.
    Sepulveda, Borja
    CSIC, Spain; BIST, Spain.
    Shahjamali, Mohammad
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering. Harvard Univ, MA 02138 USA.
    Guell-Grau, Pau
    CSIC, Spain.
    Sivlér, Petter
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Skog, Mårten
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Aronsson, Christopher
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Björk, Emma
    Linköping University, Department of Physics, Chemistry and Biology, Nanostructured Materials. Linköping University, Faculty of Science & Engineering.
    Nyberg, Niklas
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Khalaf, Hazem
    Orebro Univ, Sweden.
    Bengtsson, Torbjorn
    Orebro Univ, Sweden.
    James, Jeemol
    Univ Gothenburg, Sweden.
    Ericson, Marica B.
    Univ Gothenburg, Sweden.
    Martinsson, Erik
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Biophysics and bioengineering. Linköping University, Faculty of Science & Engineering.
    Self-Assembly of Mechanoplasmonic Bacterial Cellulose-Metal Nanoparticle Composites2020In: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 30, no 40, article id 2004766Article in journal (Refereed)
    Abstract [en]

    Nanocomposites of metal nanoparticles (NPs) and bacterial nanocellulose (BC) enable fabrication of soft and biocompatible materials for optical, catalytic, electronic, and biomedical applications. Current BC-NP nanocomposites are typically prepared by in situ synthesis of the NPs or electrostatic adsorption of surface functionalized NPs, which limits possibilities to control and tune NP size, shape, concentration, and surface chemistry and influences the properties and performance of the materials. Here a self-assembly strategy is described for fabrication of complex and well-defined BC-NP composites using colloidal gold and silver NPs of different sizes, shapes, and concentrations. The self-assembly process results in nanocomposites with distinct biophysical and optical properties. In addition to antibacterial materials and materials with excellent senor performance, materials with unique mechanoplasmonic properties are developed. The homogenous incorporation of plasmonic gold NPs in the BC enables extensive modulation of the optical properties by mechanical stimuli. Compression gives rise to near-field coupling between adsorbed NPs, resulting in tunable spectral variations and enhanced broadband absorption that amplify both nonlinear optical and thermoplasmonic effects and enables novel biosensing strategies.

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  • 30.
    Christoffersson, Jonas
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Aronsson, Christopher
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Jury, Michael
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Fabrication of modular hyaluronan-PEG hydrogels to support 3D cultures of hepatocytes in a perfused liver-on-a-chip device2019In: Biofabrication, ISSN 1758-5082, E-ISSN 1758-5090, Vol. 11, no 1, p. 1-13, article id 015013Article in journal (Refereed)
    Abstract [en]

    Liver cell culture models are attractive in both tissue engineering and for development of assays for drug toxicology research. To retain liver specific cell functions, the use of adequate cell types and culture conditions, such as a 3D orientation of the cells and a proper supply of nutrients and oxygen, are critical. In this article, we show how extracellular matrix mimetic hydrogels can support hepatocyte viability and functionality in a perfused liver-on-a-chip device. A modular hydrogel system based on hyaluronan and poly(ethylene glycol) (HA-PEG), modified with cyclooctyne moieties for bioorthogonal strain-promoted alkyne-azide 1, 3-dipolar cycloaddition (SPAAC), was developed, characterized, and compared for cell compatibility to hydrogels based on agarose and alginate. Hepatoma cells (HepG2) formed spheroids with viable cells in all hydrogels with the highest expression of albumin and urea in alginate hydrogels. By including an excess of cyclooctyne in the HA backbone, azide-modified cell adhesion motifs (linear and cyclic RGD peptides) could be introduced in order to enhance viability and functionality of human induced pluripotent stem cell derived hepatocytes (hiPS-HEPs). In the HA-PEG hydrogels modified with cyclic RGD peptides hiPS-HEPs migrated and grew in 3D and showed an increased viability and higher albumin production compared to when cultured in the other hydrogels. This flexible SPAAC crosslinked hydrogel system enabled fabrication of perfused 3D cell culture of hiPS-HEPs and is a promising material for further development and optimization of liver-on-a-chip devices.

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    Fabrication of modular hyaluronan-PEG hydrogels to support 3D cultures of hepatocytes in a perfused liver-on-a-chip device
  • 31.
    Selegard, Robert
    et al.
    Orebro Univ, Sweden.
    Musa, Amani
    Orebro Univ, Sweden.
    Nystroem, Pontus
    Orebro Univ, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Bengtsson, Torbjörn
    Orebro Univ, Sweden.
    Khalaf, Hazem
    Orebro Univ, Sweden.
    Plantaricins markedly enhance the effects of traditional antibiotics against Staphylococcus epidermidis2019In: Future Microbiology, ISSN 1746-0913, E-ISSN 1746-0921, Vol. 14, no 3, p. 195-206Article in journal (Refereed)
    Abstract [en]

    Aim: Bacteriocins are considered as promising alternatives to antibiotics against infections. In this study, the plantaricins (Pln) A, E, F, J and K were investigated for their antimicrobial activity against Staphylococcus epidermidis. Materials amp; methods: The effects on membrane integrity were studied using liposomes and viable bacteria, respectively. Results: We show that PlnEF and PlnJK caused rapid and significant lysis of S. epidermidis, and induced lysis of liposomes. The PlnEF and PlnJK displayed similar mechanisms by targeting and disrupting the bacterial cell membrane. Interestingly, Pln enhanced the effects of different antibiotics by 30- to500-fold. Conclusion: This study shows that Pln in combination with low concentrations of antibiotics is efficient against S. epidermidis and may be developed as potential treatment of infections.

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  • 32.
    Skyttner, Camilla
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Larsson, Jakob
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Aronsson, Christopher
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Enander, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Sequence and length optimization of membrane active coiled coils for triggered liposome release2019In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1862, no 2, p. 449-456Article in journal (Refereed)
    Abstract [en]

    Defined and tunable peptide-lipid membrane interactions that trigger the release of liposome encapsulated drugs may offer a route to improving the efficiency and specificity of liposome-based drug delivery systems, but this require means to tailor the performance of the membrane active peptides. In this paper, the membrane activity of a de novo designed coiled coil peptide has been optimized with respect to sequence and size to improve release efficiency of liposome encapsulated cargo. The peptides were only membrane active when covalently conjugated to the liposomes. Two amino acid substitutions were made to enhance the amphipathic characteristics of the peptide, which increased the release by a factor of five at 1 mu M. Moreover, the effect of peptide length was investigated by varying the number of heptad repeats from 2 to 5, yielding the peptides KVC2-KVC5. The shortest peptide (KVC2) showed the least interaction with the membrane and proved less efficient than the longer peptides in releasing the liposomal cargo. The peptide with three heptads (KVC3) caused liposome aggregation whereas KVC4 proved to effectively release the liposomal cargo without causing aggregation. The longest peptide (KVC5) demonstrated the most defined a-helical secondary structure and the highest liposome surface concentration but showed slower release kinetics than KVC4. The four heptad peptide KVC4 consequently displayed optimal properties for triggering the release and is an interesting candidate for further development of bioresponsive and tunable liposomal drug delivery systems.

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  • 33.
    Skog, Mårten
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Sivlér, Petter
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    The Effect of Enzymatic Digestion on Cultured Epithelial Autografts2019In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 28, no 5, p. 638-644Article in journal (Refereed)
    Abstract [en]

    Severe burns are often treated by means of autologous skin grafts, preferably following early excision of the burnt tissue. In the case of, for example, a large surface trauma, autologous skin cells can be expanded in vitro prior to transplantation to facilitate the treatment when insufficient uninjured skin is a limitation. In this study we have analyzed the impact of the enzyme (trypsin or accutase) used for cell dissociation and the incubation time on cell viability and expansion potential, as well as expression of cell surface markers indicative of stemness. Skin was collected from five individuals undergoing abdominal reduction surgery and the epidermal compartment was digested in either trypsin or accutase. Trypsin generally generated more cells than accutase and with higher viability; however, after 7 days of subsequent culture, accutase-digested samples tended to have a higher cell count than trypsin, although the differences were not significant. No significant difference was found between the enzymes in median fluorescence intensity of the analyzed stem cell markers; however, accutase digestion generated significantly higher levels of CD117- and CD49f-positive cells, but only in the 5 h digestion group. In conclusion, digestion time appeared to affect the isolated cells more than the choice of enzyme.

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  • 34.
    Ericson, Marica B.
    et al.
    Univ Gothenburg, Sweden.
    Thomsen, Hanna
    Univ Gothenburg, Sweden.
    James, Jeemol
    Univ Gothenburg, Sweden.
    Kirejev, Vladimir
    Univ Gothenburg, Sweden; Fluicell AB, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Vargas-Berenguel, Antonio
    Univ Almeria, Spain.
    Exploring plasmonic coupling as a stimuli responsive contrast mechanism in multiphoton microscopy2018In: PLASMONICS IN BIOLOGY AND MEDICINE XV, SPIE-INT SOC OPTICAL ENGINEERING , 2018, Vol. 10509, article id 1050907Conference paper (Refereed)
    Abstract [en]

    A novel approach for optical biosensing can be obtained based multiphoton induced luminescence (MIL) and its dependence on plasmonic coupling. It has been shown that the proximity of spherical AuNPs determines the generation of MIL in far-field multiphoton laser scanning microscopy (MPM). A stimuli responsive contrast mediator with high sensitivity can be created by controlling the aggregated state of AuNP. In this study we explore a system based on spherical AuNPs functionalized with beta-cyclodextrin and multiple beta-D-lactose units (lacto-CD-AuNP). The aim of the beta-D- lactose units is to target cancer cells, based on overexpression of galectin3 (Gal-3) receptors. The results demonstrate that clustering of particles, and thereby MIL signal, was only acquired from tumor cell lines, i.e., SK-MEL-28 and A431, while not from normal keratinocytes (HEKn). Thus further studies should be undertaken to translate the concept to a preclinical setting.

  • 35.
    Fursatz, Marian
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Skog, Mårten
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering. S2Med AB, Linnegatan 9, SE-58225 Linkoping, Sweden.
    Sivlér, Petter
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering. S2Med AB, Linnegatan 9, SE-58225 Linkoping, Sweden.
    Palm, Eleonor
    Orebro Univ, Sweden.
    Aronsson, Christopher
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Skallberg, Andreas
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Greczynski, Grzegorz
    Linköping University, Department of Physics, Chemistry and Biology, Thin Film Physics. Linköping University, Faculty of Science & Engineering.
    Khalaf, Hazem
    Orebro Univ, Sweden.
    Bengtsson, Torbjorn
    Orebro Univ, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Functionalization of bacterial cellulose wound dressings with the antimicrobial peptide epsilon-poly-L-Lysine2018In: Biomedical Materials, ISSN 1748-6041, E-ISSN 1748-605X, Vol. 13, no 2, article id 025014Article in journal (Refereed)
    Abstract [en]

    Wound dressings based on bacterial cellulose (BC) can form a soft and conformable protective layer that can stimulate wound healing while preventing bacteria from entering the wound. Bacteria already present in the wound can, however, thrive in the moist environment created by the BC dressing which can aggravate the healing process. Possibilities to render the BC antimicrobial without affecting the beneficial structural and mechanical properties of the material would hence be highly attractive. Here we present methods for functionalization of BC with epsilon-poly-L-Lysine (epsilon-PLL), a non-toxic biopolymer with broad-spectrum antimicrobial activity. Low molecular weight epsilon-PLL was crosslinked in pristine BC membranes and to carboxymethyl cellulose functionalized BC using carbodiimide chemistry. The functionalization of BC with epsilon-PLL inhibited growth of S. epidermidis on the membranes but did not affect the cytocompatibility to cultured human fibroblasts as compared to native BC. The functionalization had no significant effects on the nanofibrous structure and mechanical properties of the BC. The possibility to functionalize BC with epsilon-PLL is a promising, green and versatile approach to improve the performance of BC in wound care and other biomedical applications.

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  • 36.
    Chen, Peng
    et al.
    Nanyang Technol Univ, Singapore.
    Liu, Xiaohu
    Nanyang Technol Univ, Singapore; Tsinghua Univ, Peoples R China.
    Goyal, Garima
    Nanyang Technol Univ, Singapore.
    Tran, Nhung Thi
    Nanyang Technol Univ, Singapore; Ho Chi Minh City Univ Technol and Educ, Vietnam.
    Ho, James Chin Shing
    Nanyang Technol Univ, Singapore.
    Wang, Yi
    Nanyang Technol Univ, Singapore; Wenzhou Med Univ, Peoples R China.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Liedbereg, Bo
    Nanyang Technol Univ, Singapore; Nanyang Technol Univ, Singapore.
    Nanoplasmonic Sensing from the Human Vision Perspective2018In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 90, no 7, p. 4916-4924Article in journal (Refereed)
    Abstract [en]

    Localized surface plasmon resonance (LSPR) constitutes a versatile technique for biodetection, exploiting the sensitivity of plasmonic nanostructures to small changes in refractive index. The optical shift in the LSPR band caused by molecular interactions in the vicinity of the nanostructures are typically amp;lt;5 nm and can readily be detected by a spectrophotometer. Widespread use of LSPR-based sensors require cost-effective devices and would benefit from sensing schemes that enables use of very simple spectrophotometers or even naked-eye detection. This paper describes a new strategy facilitating visualization of minute optical responses in nanoplasmonic bioassays by taking into account the physiology of human color vision. We demonstrate, using a set of nine different plasmonic nanoparticles, that the cyan to green transition zone at similar to 500 nm is optimal for naked-eye detection of color changes. In this wavelength range, it is possible to detect a color change corresponding to a wavelength shift of similar to 2-3 nm induced by refractive index changes in the medium or by molecular binding to the surface of the nanoparticles. This strategy also can be utilized to improve the performance of aggregation-based nanoplasmonic colorimetric assays, which enables semiquantitative naked-eye detection of matrix metalloproteinase 7 (MMP7) activity at concentrations that are at least 5 times lower than previously reported assays using spherical gold nanoparticles. We foresee significant potential of this strategy in medical diagnostic and environmental monitoring, especially in situations where basic laboratory infrastructure is sparse or even nonexistent. Finally, we demonstrate that the developed concept can be used in combination with cell phone technology and red-green-blue (RGB) analysis for sensitive and quantitative detection of MMP7.

  • 37.
    Rouhbakhsh, Zeinab
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering. Ferdowsi University of Mashhad, Mashhad, Iran.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Martinsson, Erik
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Svärd, Anna
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Bäck, Marcus
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Housaindokht, Mohammad R.
    Ferdowsi University of Mashhad, Mashhad, Iran.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Self-Assembly of a Structurally Defined Chiro-Optical Peptide-Oligothiophene Hybrid Material2018In: ACS Omega, E-ISSN 2470-1343, Vol. 3, no 11, p. 15066-15075Article in journal (Refereed)
    Abstract [en]

    Conducting polymers are routinely used in optoelectronic biomaterials, but large polymer polydispersity and poor aqueous compatibility complicate integration with biomolecular templates and development of discrete and defined supramolecular complexes. Herein, we report on a chiro-optical hybrid material generated by the self-assembly of an anionic peptide and a chemically defined cationic pentameric thiophene in aqueous environment. The peptide acts as a stereochemical template for the thiophene and adopts an a-helical conformation upon association, inducing optical activity in the thiophene r-n * transition region. Theoretical calculations confirm the experimentally observed induced structural changes and indicate the importance of electrostatic interactions in the complex. The association process is also probed at the substrate-solvent interface using peptide-functionalized gold nanoparticles, indicating that the peptide can also act as a scaffold when immobilized, resulting in structurally well-defined supramolecular complexes. The hybrid complex could rapidly be assembled, and the kinetics of the formation could be monitored by utilizing the local surface plasmon resonance originating from the gold nanoparticles. We foresee that these findings will aid in designing novel hybrid materials and provide a possible route for the development of functional optoelectronic interfaces for both biomaterials and energy harvesting applications.

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  • 38.
    Sivler, Tobias
    et al.
    S2Medical AB, Sunnorpsgatan, Linkoping, Sweden.
    Sivlér, Petter
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering. S2Medical AB, Sunnorpsgatan, Linkoping, Sweden.
    Skog, Mårten
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering. S2Medical AB, Sunnorpsgatan, Linkoping, Sweden.
    Conti, Luca
    S2Medical AB, Sunnorpsgatan, Linkoping, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Treatment of Nonhealing Ulcers with an Allograft/Xenograft Substitute: A Case Series2018In: Advances in Skin & Wound Care, ISSN 1527-7941, E-ISSN 1538-8654, Vol. 31, no 7, p. 306-309Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Wound dressings that use biosynthetic cellulose may be a good alternative to dressings currently used to treat chronic and acute ulcers because their nanostructure is similar to collagen. The objective of this study was to evaluate a wound dressing created with a new material that is composed of a fibrillary network of biosynthetic cellulose. METHODS: A case series of 8 patients in primary healthcare centers in ostergotland county council, Sweden, with chronic and acute lower limb wounds were treated with a wound dressing based on eiratex (S2Medical AB, Linkoping, Sweden). The dressing was applied to traumatic (n = 5) and venous ulcers (n = 3). All ulcers were considered healed at the end of the treatment. MAIN OUTCOME MEASURE: The wounds were examined at regular intervals by a physician to determine healing time, number of dressing changes, and number of visits. MAIN RESULTS: Mean healing time was 43 6 days after the first application of the dressing. The mean number of visits was 5.7 +/- 0.6, and the mean number of dressings used per patient was 1.7 +/- 0.2. CONCLUSIONS: These results demonstrate the efficacy of a wound dressing made of eiratex to heal chronic and acute ulcers. The data show that the number of dressings used and dressing changes needed to heal the ulcers are lower than what have been reported in the literature for other dressing materials.

  • 39.
    Skyttner, Camilla
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Enander, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Aronsson, Christopher
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Tuning Liposome Membrane Permeability by Competitive Coiled Coil Heterodimerization and Heterodimer Exchange2018In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 34, no 22, p. 6529-6537Article in journal (Refereed)
    Abstract [en]

    Membrane-active peptides that enable the triggered release of liposomal cargo are of great interest for the development of liposome-based drug delivery systems but require peptide-lipid membrane interactions that are highly defined and tunable. To this end, we have explored the possibility to use the competing interactions between membrane partitioning and heterodimenzation and the folding of a set of four different de novo designed coiled coil peptides Covalent conjugation of the cationic peptides triggered rapid destabilization of membrane mtegrity and the release of encapsulated species. The release was inhibited when introducing complementary peptides as a result of heterodimenzation and folding into coiled mils The degree of inhibition was shown to be dictated by the coiled coil peptide heterodimer dissociation constants, and liposomal release could be reactivated by a heterodimer exchange to render the membrane bound peptide free and thus membrane-active. The possibility to tune the permeability of lipid membranes using highly specific peptide-folding-dependent interactions delineates a new possible approach for the further development of responsive liposome-based drug delivery systems.

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  • 40.
    Selegård, Robert
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Rouhbalchsh, Zeinab
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Shirani, Hamid
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Johansson, Leif
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Norman, Patrick
    KTH Royal Institute Technology, Sweden.
    Linares, Mathieu
    KTH Royal Institute Technology, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Distinct Electrostatic Interactions Govern the Chiro-Optical Properties and Architectural Arrangement of Peptide-Oligothiophene Hybrid Materials2017In: Macromolecules, ISSN 0024-9297, E-ISSN 1520-5835, Vol. 50, no 18, p. 7102-7110Article in journal (Refereed)
    Abstract [en]

    The development of chiral optoelectronic materials is of great interest due to their potential of being utilized in electronic devices, biosensors, and artificial enzymes. Herein, we report the chiral optical properties and architectural arrangement of optoelectronic materials generated from noncovalent self-assembly of a cationic synthetic peptide and five chemically defined anionic pentameric oligothiophenes. The peptide-oligothiophene hybrid materials exhibit a three-dimensional ordered helical structure and optical activity in the pi-pi* transition region that are observed due to a single chain induced chirality of the conjugated thiophene backbone upon interaction with the peptide. The latter property is highly dependent on electrostatic interactions between the peptide and the oligothiophene, verifying that a distinct spacing of the carboxyl groups along the thiophene backbone is a major chemical determinant for having a hybrid material with distinct optoelectronic properties. The necessity of the electrostatic interaction between specific carboxyl functionalities along the thiophene backbone and the lysine residues of the peptide, as well as the induced circular dichroism of the thiophene backbone, was also confirmed by theoretical calculations. We foresee that our findings will aid in designing optoelectronic materials with dynamic architectonical precisions as well as offer the possibility to create the next generation of materials for organic electronics and organic bioelectronics.

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  • 41.
    Bengtsson, Torbjörn
    et al.
    Örebro University, Sweden.
    Zhang, Boxi
    Karolinska Institutet, Sweden.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering. Örebro University, Sweden.
    Wiman, Emanuel
    Örebro University, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Khalaf, Hazem
    Örebro University, Sweden.
    Dual action of bacteriocin PLNC8 alpha beta through inhibition of Porphyromonas gingivalis infection and promotion of cell proliferation2017In: Pathogens and Disease, E-ISSN 2049-632X, Vol. 75, no 5, article id ftx064Article in journal (Refereed)
    Abstract [en]

    Periodontitis is a chronic inflammatory disease that is characterised by accumulation of pathogenic bacteria, including Porphyromonas gingivalis, in periodontal pockets. The lack of effective treatments has emphasised in an intense search for alternative methods to prevent bacterial colonisation and disease progression. Bacteriocins are bacterially produced antimicrobial peptides gaining increased consideration as alternatives to traditional antibiotics. We show rapid permeabilisation and aggregation of P. gingivalis by the two-peptide bacteriocin PLNC8 alpha beta. In a cell culture model, P. gingivalis was cytotoxic against gingival fibroblasts. The proteome profile of fibroblasts is severely affected by P. gingivalis, including induction of the ubiquitin-proteasome pathway. PLNC8 alpha beta enhanced the expression of growth factors and promoted cell proliferation, and suppressed proteins associated with apoptosis. PLNC8 alpha beta efficiently counteracted P. gingivalis-mediated cytotoxicity, increased expression of a large number of proteins and restored the levels of inflammatory mediators. In conclusion, we show that bacteriocin PLNC8 alpha beta displays dual effects by acting as a potent antimicrobial agent killing P. gingivalis and as a stimulatory factor promoting cell proliferation. We suggest preventive and therapeutical applications of PLNC8 alpha beta in periodontitis to supplement the host immune defence against P. gingivalis infection and support wound healing processes.

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  • 42.
    Selegård, Robert
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Aronsson, Christopher
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Brommesson, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Dånmark, Staffan
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Folding driven self-assembly of a stimuli-responsive peptide-hyaluronan hybrid hydrogel2017In: Scientific Reports, E-ISSN 2045-2322, Vol. 7, article id 7013Article in journal (Refereed)
    Abstract [en]

    Protein-metal ion interactions are ubiquitous in nature and can be utilized for controlling the self-assembly of complex supramolecular architectures and materials. Here, a tunable supramolecular hydrogel is described, obtained by self-assembly of a Zn2+-responsive peptide-hyaluronic acid hybrid synthesized using strain promoted click chemistry. Addition of Zn2+ triggers folding of the peptides into a helix-loop-helix motif and dimerization into four-helix bundles, resulting in hydrogelation. Removal of the Zn2+ by chelators results in rapid hydrogel disassembly. Degradation of the hydrogels can also be time-programed by encapsulation of a hydrolyzing enzyme within the gel, offering multiple possibilities for modulating materials properties and release of encapsulated species. The hydrogel further shows potential antioxidant properties when evaluated using an in vitro model for reactive oxygen species.

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  • 43.
    Borglin, Johan
    et al.
    University of Gothenburg, Sweden.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Ericson, Marica B.
    University of Gothenburg, Sweden.
    Peptide Functionalized Gold Nanoparticles as a Stimuli Responsive Contrast Medium in Multiphoton Microscopy2017In: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 17, no 3, p. 2102-2108Article in journal (Refereed)
    Abstract [en]

    There is a need for biochemical contrast mediators with high signal-to-noise ratios enabling noninvasive biomedical sensing, for example, for neural sensing and protein protein interactions, in addition to cancer diagnostics. The translational challenge is to develop a biocompatible approach ensuring high biochemical contrast while avoiding a raise of the background signal. We here present a concept where gold nanoparticles (AuNPs) can be utilized as a stimuli responsive contrast medium by chemically triggering their ability to exhibit multiphoton-induced luminescence (MIL) when performing multiphoton laser scanning microscopy (MPM). Proof-of-principle is demonstrated using peptide-functionalized AuNPs sensitive to zinc ions (Zn2+). Dispersed particles are invisible in the MPM until addition of millimolar concentrations of Zn2+ upon which MIL is enabled through particle aggregation caused by specific peptide interactions and folding. The process can be reversed by removal of the Zn2+ using a chelator, thereby resuspending the AuNPs. In addition, the concept was demonstrated by exposing the particles to matrix metalloproteinase-7 (MMP-7) causing peptide digestion resulting in AuNP aggregation, significantly elevating the MIL signal from the background. The approach is based on the principle that aggregation shifts the plasmon resonance, elevating the absorption cross section in the near-infrared wavelength region enabling onset of MIL. This Letter demonstrates how biochemical sensing can be obtained in far-field MPM and should be further exploited as a future tool for noninvasive optical biosensing.

  • 44.
    Khalaf, Hazem
    et al.
    University of Örebro, Sweden.
    Sowdamini Nakka, Sravya
    University of Örebro, Sweden; PEAS Institute AB, Soderleden 1, Linkoping, Sweden.
    Sandén, Camilla
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Svärd, Anna
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Hultenby, Kjell
    Karolinska Institute, Sweden.
    Scherbak, Nikolai
    University of Örebro, Sweden.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Bengtsson, Torbjorn
    University of Örebro, Sweden.
    Antibacterial effects of Lactobacillus and bacteriocin PLNC8 alpha beta on the periodontal pathogen Porphyromonas gingivalis2016In: BMC Microbiology, E-ISSN 1471-2180, Vol. 16, no 188Article in journal (Refereed)
    Abstract [en]

    Background: The complications in healthcare systems associated with antibiotic-resistant microorganisms have resulted in an intense search for new effective antimicrobials. Attractive substances from which novel antibiotics may be developed are the bacteriocins. These naturally occurring peptides are generally considered to be safe and efficient at eliminating pathogenic bacteria. Among specific keystone pathogens in periodontitis, Porphyromonas gingivalis is considered to be the most important pathogen in the development and progression of chronic inflammatory disease. The aim of the present study was to investigate the antimicrobial effects of different Lactobacillus species and the two-peptide bacteriocin PLNC8 alpha beta on P. gingivalis. Results: Growth inhibition of P. gingivalis was obtained by viable Lactobacillus and culture media from L. plantarum NC8 and 44048, but not L. brevis 30670. The two-peptide bacteriocin from L. plantarum NC8 (PLNC8 alpha beta) was found to be efficient against P. gingivalis through binding followed by permeabilization of the membranes, using Surface plasmon resonance analysis and DNA staining with Sytox Green. Liposomal systems were acquired to verify membrane permeabilization by PLNC8 alpha beta. The antimicrobial activity of PLNC8 alpha beta was found to be rapid (1 min) and visualized by TEM to cause cellular distortion through detachment of the outer membrane and bacterial lysis. Conclusion: Soluble or immobilized PLNC8 alpha beta bacteriocins may be used to prevent P. gingivalis colonization and subsequent pathogenicity, and thus supplement the host immune system against invading pathogens associated with periodontitis.

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  • 45.
    Chen, Hu
    et al.
    Nanyang Technology University, Singapore; Nanyang Technology University, Singapore; University of Loughborough, England.
    Chen, Peng
    Nanyang Technology University, Singapore; Centre Biomimet Sensor Science, Singapore.
    Huang, Jingfeng
    Nanyang Technology University, Singapore; Nanyang Technology University, Singapore.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Platt, Mark
    University of Loughborough, England.
    Palaniappan, Alagappan
    Nanyang Technology University, Singapore; Centre Biomimet Sensor Science, Singapore.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Iing Yoong Tok, Alfred
    Nanyang Technology University, Singapore; Nanyang Technology University, Singapore.
    Liedberg, Bo
    Nanyang Technology University, Singapore; Centre Biomimet Sensor Science, Singapore.
    Detection of Matrilysin Activity Using Polypeptide Functionalized Reduced Graphene Oxide Field-Effect Transistor Sensor2016In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 88, no 6, p. 2994-2998Article in journal (Refereed)
    Abstract [en]

    A novel approach for rapid and sensitive detection of matrilysin (MMP-7, a biomarker involved in the degradation of various macromolecules) based on a polypeptide (JR2EC) functionalized reduced graphene oxide (rGO) field effect transistor (FET) is reported. MMP-7 specifically digests negatively charged JR2EC immobilized on rGO, thereby modulating the conductance of rGO-FET. The proposed assay enabled detection of MMP-7 at clinically relevant concentrations with a limit of detection (LOD) of 10 ng/mL (400 pM), attributed to the significant reduction of the net charge of JR2EC upon digestion by MMP-7. Quantitative detection of MMP-7 in human plasma was further demonstrated with a LOD of 40 ng/mL, illustrating the potential for the proposed methodology for tumor detection and carcinoma diagnostic (e.g., lung cancer and salivary gland cancer). Additionally, excellent specificity of the proposed assay was demonstrated using matrix metallopeptidase 1 (MMP-1), a protease of the same family. With appropriate selection and modification of polypeptides, the proposed assay could be extended for detection of other enzymes with polypeptide digestion capability.

  • 46.
    Wickham, Abeni
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Vagin, Mikhail
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, Faculty of Science & Engineering.
    Khalaf, Hazem
    University of Örebro, Sweden.
    Bertazzo, Sergio
    UCL, England.
    Hodder, Peter
    TA Instruments Ltd, England.
    Dånmark, Staffan
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Bengtsson, Torbjorn
    University of Örebro, Sweden.
    Altimiras, Jordi
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Electroactive biomimetic collagen-silver nanowire composite scaffolds2016In: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 8, no 29, p. 14146-14155Article in journal (Refereed)
    Abstract [en]

    Electroactive biomaterials are widely explored as bioelectrodes and as scaffolds for neural and cardiac regeneration. Most electrodes and conductive scaffolds for tissue regeneration are based on synthetic materials that have limited biocompatibility and often display large discrepancies in mechanical properties with the surrounding tissue causing problems during tissue integration and regeneration. This work shows the development of a biomimetic nanocomposite material prepared from self-assembled collagen fibrils and silver nanowires (AgNW). Despite consisting of mostly type I collagen fibrils, the homogeneously embedded AgNWs provide these materials with a charge storage capacity of about 2.3 mC cm(-2) and a charge injection capacity of 0.3 mC cm(-2), which is on par with bioelectrodes used in the clinic. The mechanical properties of the materials are similar to soft tissues with a dynamic elastic modulus within the lower kPa range. The nanocomposites also support proliferation of embryonic cardiomyocytes while inhibiting the growth of both Gram-negative Escherichia coli and Gram-positive Staphylococcus epidermidis. The developed collagen/AgNW composites thus represent a highly attractive bioelectrode and scaffold material for a wide range of biomedical applications.

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  • 47.
    Martinsson, Erik
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering. Northwestern University, IL 60208 USA.
    Shahjamali, Mohammad M.
    Nanyang Technology University, Singapore.
    Large, Nicolas
    Northwestern University, IL 60208 USA.
    Zaraee, Negin
    Northwestern University, IL 60208 USA.
    Zhou, Yu
    Northwestern University, IL 60208 USA.
    Schatz, George C.
    Northwestern University, IL 60208 USA.
    Mirkin, Chad A.
    Northwestern University, IL 60208 USA.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Influence of Surfactant Bilayers on the Refractive Index Sensitivity and Catalytic Properties of Anisotropic Gold Nanoparticles2016In: Small, ISSN 1613-6810, E-ISSN 1613-6829, Vol. 12, no 3, p. 330-342Article in journal (Refereed)
    Abstract [en]

    Shape-controlled synthesis of gold nanoparticles generally involves the use of surfactants, typically cetyltrimethylammonium (CTAX, X = Cl-, Br-), to regulate the nucleation growth process and to obtain colloidally stable nanoparticles. The surfactants adsorb on the nanoparticle surface making further functionalization difficult and therefore limit their use in many applications. Herein, the influence of CTAX on nanoparticle sensitivity to local dielectric environment changes is reported. It is shown, both experimentally and theoretically, that the CTAX bilayer significantly reduces the refractive index (RI) sensitivity of anisotropic gold nanoparticles such as nanocubes and concave nanocubes, nanorods, and nanoprisms. The RI sensitivity can be increased by up to 40% by removing the surfactant layer from nanoparticles immobilized on a solid substrate using oxygen plasma treatment. This increase compensates for the otherwise problematic decrease in RI sensitivity caused by the substrate effect. Moreover, the removal of the surfactants both facilitates nanoparticle biofunctionalization and significantly improves their catalytic properties. The strategy presented herein is a simple yet effective universal method for enhancing the RI sensitivity of CTAX-stabilized gold nanoparticles and increasing their potential as transducers in nanoplasmonic sensors, as well as in catalytic and biomedical applications.

  • 48.
    Dånmark, Staffan
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Aronsson, Christopher
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Tailoring Supramolecular Peptide-Poly(ethylene glycol) Hydrogels by Coiled Coil Self-Assembly and Self-Sorting2016In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 17, no 6, p. 2260-2267Article in journal (Refereed)
    Abstract [en]

    Physical hydrogels are extensively used in a wide range of biomedical applications. However, different applications require hydrogels with different mechanical and structural properties. Tailoring these properties demands exquisite control over the supramolecular peptides with different affinities for dimerization. Four different mechanical properties of hydrogels using de novo designed coiled coil interactions involved. Here we show that it is possible to control the nonorthogonal peptides, designed to fold into four different coiled coil heterodimers with dissociation constants spanning from mu M to pM, were conjugated to star-shaped 4-arm poly(ethylene glycol) (PEG). The different PEG-coiled coil conjugates self-assemble as a result of peptide heterodimerization. Different combinations of PEG peptide conjugates assemble into PEG peptide networks and hydrogels with distinctly different thermal stabilities, supramolecular, and rheological properties, reflecting the peptide dimer affinities. We also demonstrate that it is possible to rationally modulate the self-assembly process by means of thermodynamic self-sorting by sequential additions of nonpegylated peptides. The specific interactions involved in peptide dimerization thus provides means for programmable and reversible self-assembly of hydrogels with precise control over rheological properties, which can significantly facilitate optimization of their overall performance and adaption to different processing requirements and applications.

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  • 49.
    Koon Lim, Seng
    et al.
    Nanyang Technology University, Singapore.
    Sandén, Camilla
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Liedberg, Bo
    Nanyang Technology University, Singapore.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Tuning Liposome Membrane Permeability by Competitive Peptide Dimerization and Partitioning-Folding Interactions Regulated by Proteolytic Activity2016In: Scientific Reports, E-ISSN 2045-2322, Vol. 6, no 21123, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Membrane active peptides are of large interest for development of drug delivery vehicles and therapeutics for treatment of multiple drug resistant infections. Lack of specificity can be detrimental and finding routes to tune specificity and activity of membrane active peptides is vital for improving their therapeutic efficacy and minimize harmful side effects. We describe a de novo designed membrane active peptide that partition into lipid membranes only when specifically and covalently anchored to the membrane, resulting in pore-formation. Dimerization with a complementary peptide efficiently inhibits formation of pores. The effect can be regulated by proteolytic digestion of the inhibitory peptide by the matrix metalloproteinase MMP-7, an enzyme upregulated in many malignant tumors. This system thus provides a precise and specific route for tuning the permeability of lipid membranes and a novel strategy for development of recognition based membrane active peptides and indirect enzymatically controlled release of liposomal cargo.

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  • 50.
    Aronsson, Christopher
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Selegård, Robert
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Zinc-Triggered Hierarchical Self-Assembly of Fibrous Helix-Loop-Helix Peptide Superstructures for Controlled Encapsulation and Release2016In: Macromolecules, ISSN 0024-9297, E-ISSN 1520-5835, Vol. 49, no 18, p. 6997-7003Article in journal (Refereed)
    Abstract [en]

    We demonstrate a novel route for hierarchical self-assembly of sub-micrometer-sized peptide superstructures that respond to subtle changes in Zn2+ concentration. The self-assembly process is triggered by a specific folding-dependent coordination of Zn2+ by a de novo designed nonlinear helix-loop-helix peptide, resulting in a propagating fiber formation and formation of spherical superstructures. The superstructures further form larger assemblies that can be completely disassembled upon removal of Zn2+ or degradation of the nonlinear peptide. This flexible and reversible assembly strategy of the superstructures enables facile encapsulation of nanoparticles and drugs that can be released by means of different stimuli.

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