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  • 101.
    Mindemark, Jonas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Törmä, Erik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Sun, Bing
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Brandell, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Copolymers of trimethylene carbonate and epsilon-caprolactone as electrolytes for lithium-ion batteries2015Inngår i: Polymer, ISSN 0032-3861, E-ISSN 1873-2291, Vol. 63, s. 91-98Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Random copolymers of trimethylene carbonate (TMC) and epsilon-caprolactone (CL) were synthesized through bulk ring-opening polymerization for use as host materials for solid polymer electrolytes. Amorphous electrolytes were solution-cast from the copolymers together with LiTFSI salt and showed lower T-g and higher ionic conductivity as the CL content was increased. The best-performing electrolyte, with a TMC:CL ratio of 60:40 with 28 wt% of LiTFSI, was found to have a conductivity of 1.6 x 10(-5) S cm(-1) at 60 degrees C (7.9 x 10(-7) S cm(-1) at 25 degrees C) and a T-g of -26 degrees C. This electrolyte was used in all-solid-state LiFePO4 half-cells that showed high capacity and coulombic efficiency at rates up to and including C/5.

  • 102. Nageeb, Mohamad
    et al.
    Nouh, Samir R.
    Bergman, Kristoffer
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Nagy, Naglaa B.
    Khamis, Dalia
    Kisiel, Marta
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Engstrand, Thomas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Marei, Mona K.
    Bone Engineering by Biomimetic Injectable Hydrogel2012Inngår i: Molecular Crystals and Liquid Crystals, ISSN 1542-1406, Vol. 555, nr 1, s. 177-188Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Osteoporosis is a multifactorial bone disease characterized by low bone mineral density (BMD) and deterioration of micro-architecture of cancellous bone leading to bone fragility and risk of fractures. In the current work, a novel tissue engineering strategy was experimented to enhance bone architecture in the risk areas via local injection of a biomimetic/osteoinductive injectable hyaluronan based hydrogel loaded with nano-hydroxyapatite crystals (Hya/HA) with/without bone morphogenetic protein (BMP-2), in distal femur of normal and ovariectomized New Zealand white rabbits. Our results revealed the osteoinductive effect of the Hya/HA composite that enhanced bone density and architecture of the rabbit distal femur.

  • 103.
    Nederberg, Fredrik
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Watanabe, Junji
    Ishihara, Kazuhiko
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Bowden, Tim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Biocompatible and biodegradable phosphorylcholine ionomers with reduced protein adsorption and cell adhesion2006Inngår i: Journal of Biomaterials Science. Polymer Edition, ISSN 0920-5063, E-ISSN 1568-5624, Vol. 17, nr 6, s. 605-614Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this paper a recently developed biodegradable phosphorylcholine ionomer (PC ionomer) was evaluated in different biological environments with a focus on the adsorption of proteins (fibrinogen) and the adhesion of cells. Our results have shown that the polar phosphoryl choline (PC) group may be enriched at the surface of cast films with an added hydrophilic environment. X-ray photoelectron spectroscopy confirmed the surface depletion of PC groups in dry conditions, as nitrogen and phosphorous atoms were found in the bulk of the material but not at the outermost surface layer. The surface enrichment leads to a strongly hydrophilic surface that prevents the adsorption of proteins and reduces the adhesion of cells. The non-functional and hydrophobic reference poly(trimethylene carbonate) (PTMC) adsorbs both proteins and cells, thus the wetting and low adhesion behavior of the PC ionomer can be attributed to the introduced PC functionality. Since the in vivo acceptance of biomaterials is determined by their ability to withstand protein adsorption the PC ionomer described in this paper is highly interesting for a number of in vivo applications in which the adsorption of proteins may be critical, for example, blood contact events.

  • 104. Nejadnik, M. Reza
    et al.
    Yang, Xia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Bongio, Mattilde
    Alghamdi, Hamdan S.
    van den Beucken, Jeroen J. J. P.
    Huysmans, Marie C.
    Jansen, John A.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Ossipov, Dmitri
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Leeuwenburgh, Sander C. G.
    Self-healing Hybrid Nanocomposites consisting of Bisphosphonated Hyaluronan and Calcium Phosphate Nanoparticles2014Inngår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, nr 25, s. 6918-6929Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Non-covalent interactions are often regarded as insufficient to construct macroscopic materials of substantial integrity and cohesion. However, the low binding energy of such reversible interactions can be compensated by increasing their number to work in concert to create strong materials. Here we present the successful development of an injectable, cohesive nanocomposite hydrogel based on reversible bonds between calcium phosphate nanoparticles and bisphosphonate-functionalized hyaluronic acid. These nanocomposites display a capacity for self-healing as well as adhesiveness to mineral surfaces such as enamel and hydroxyapatite. Most importantly, these non-covalently cross-linked composites are surprisingly robust yet biodegradable upon extensive in vitro and in vivo testing and show bone interactive capacity evidenced by bone ingrowth into material remnants. The herein presented method provides a new methodology for constructing nanoscale composites for biomedical applications, which owe their integrity to reversible bonds.

  • 105.
    Nicholls, Ian A.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Chavan, Swapnil
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Golker, Kerstin
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Karlsson, Björn C. G.
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Olsson, Gustaf D.
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Rosengren, Annika M.
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Suriyanarayanan, Subramanian
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Wiklander, Jesper G.
    Linnaeus Univ, Bioorgan & Biophys Chem Lab, Ctr Biomat Chem, Dept Chem & Biomed, S-39182 Kalmar, Sweden..
    Theoretical and Computational Strategies for the Study of the Molecular Imprinting Process and Polymer Performance2015Inngår i: Molecularly Imprinted Polymers In Biotechnology, Cham, Switzerland: Springer, 2015, s. 25-50Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    The development of in silico strategies for the study of the molecular imprinting process and the properties of molecularly imprinted materials has been driven by a growing awareness of the inherent complexity of these systems and even by an increased awareness of the potential of these materials for use in a range of application areas. Here we highlight the development of theoretical and computational strategies that are contributing to an improved understanding of the mechanisms underlying molecularly imprinted material synthesis and performance, and even their rational design.

  • 106.
    Olsson, Gustaf D.
    et al.
    Linnaeus Univ, Linnaeus Ctr Biomat Chem, S-39182 Kalmar, Sweden..
    Niedergall, Klaus
    Fraunhofer Inst Interfacial Engn & Biotechnol IGB, Stuttgart, Germany..
    Bach, Monika
    Fraunhofer Inst Interfacial Engn & Biotechnol IGB, Stuttgart, Germany.;Univ Stuttgart, Inst Interfacial Engn & Plasmatechnol IGVT, D-70174 Stuttgart, Germany..
    Karlsson, Björn C. G.
    Linnaeus Univ, Linnaeus Ctr Biomat Chem, S-39182 Kalmar, Sweden..
    Tovar, Guenter
    Fraunhofer Inst Interfacial Engn & Biotechnol IGB, Stuttgart, Germany.;Univ Stuttgart, Inst Interfacial Engn & Plasmatechnol IGVT, D-70174 Stuttgart, Germany..
    Nicholls, Ian A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi. Linnaeus Univ, Linnaeus Ctr Biomat Chem, S-39182 Kalmar, Sweden..
    Simulation of imprinted emulsion prepolymerization mixtures2015Inngår i: Polymer journal, ISSN 0032-3896, E-ISSN 1349-0540, Vol. 47, nr 12, s. 827-830Artikkel i tidsskrift (Fagfellevurdert)
  • 107.
    Ossipov, Dmitri A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Nanostructured hyaluronic acid-based materials for active delivery to cancer2010Inngår i: Expert Opinion on Drug Delivery, ISSN 1742-5247, E-ISSN 1744-7593, Vol. 7, nr 6, s. 681-703Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Importance of the field: Active targeting of bioactive molecules by physicochemical association with hyaluronic acid ( HA) is an attractive approach in current nanomedicine because HA is biocompatible, non-toxic and non-inflammatory. Areas covered in this review: This review focuses on synthesis, physicochemical characterization and biological properties of different nanoparticulate delivery systems that include HA in their structures. Chemically based approaches to the delivery of small molecule drugs, proteins and nucleic acids in which they become chemically or physically bound to hyaluronic acid are reviewed, including the use of molecular HA conjugates and nanocarriers. The systems are considered in terms of intracellular delivery to different cultured cells that express HA-specific receptors (hyaladherines) differently. The in vivo biodistribution and therapeutic effect of these systems are discussed. What the reader will gain: Different synthetic methodologies for preparations of HA-based nanoparticles are presented extensively. HA nanoparticulate systems of various structures can be compared with respect to their in vitro assays and in vivo biodistribution. Take home message: To make HA useful as an intravenous targeting carrier, strategies have to be devised to: reduce HA clearance from the blood; suppress the HA uptake by liver and spleen; and provide tumor-triggered mechanisms of release of an active drug from the HA carrier.

  • 108.
    Ossipov, Dmitri A.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Blasi Romero, Anna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Ossipova, Elena
    Karolinska Inst, Dept Med, Rheumatol Unit, SE-17176 Stockholm, Sweden.
    Light-activatable prodrugs based on hyaluronic acid biomaterials2018Inngår i: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 180, s. 145-155Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Photosensitive in situ cross-linked hyaluronan (HA) hydrogels are prepared by modular chemoselective assembly from the biopolymer precursors and novel heterobifunctional linkers with middle photo-labile ortho-nitrobenzyl group and orthogonally reactive terminals. Starting from the thiol-modified HA and a linker with activated disulfide and hydrazide terminals, a photo-degradable HA hydrogel was prepared by the hydrazone cross-linking reaction. Moreover, a light-triggered drug-releasing hydrogel prodrug was constructed by an orthogonal conjugation of dopamine (DA) via a photo-labile linker to HA dually modified with thiol and hydrazide groups (hy-HA-SH) and a subsequent cross-linking with aldehyde-derivatized HA (HA-al). On-demand release of DA from the hydrogel was achieved upon exposure of the hydrogel to UV light whereas 11-fold less release of the drug was observed in the absence of light. The mechanical properties of the hydrogels, photodegradation kinetics, photorelease of the model drugs were studied by rheology, spectrophotometry, chromatography, and mass spectrometry. For the first time, integration of photolabile components into an actual polysaccharide of extracellular matrix was implemented for the light-controlled release of drug molecules.

  • 109.
    Ossipov, Dmitri A.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Piskounova, Sonya
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Varghese, Oommen P.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Functionalization of Hyaluronic Acid with Chemoselective Groups via a Disulfide-Based Protection Strategy for In Situ Formation of Mechanically Stable Hydrogels2010Inngår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 11, nr 9, s. 2247-2254Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Functionalization of hyaluronic acid (HA) with chemoselective groups enables in situ (in vivo) formation of HA-based materials in minimally invasive injectable manner. Current methods of HA modification with such groups primarily rely on the use of a large excess of a reagent to introduce a unique reactive handle into HA and, therefore, are difficult to control. We have developed the new protective group strategy based on initial mild cleavage of a disulfide bond followed by elimination of the generated 2-thioethoxycarbonyl moiety ultimately affording free amine-type functionality, such as hydrazide, aminooxy, and carbazate. Specifically, new modifying homobifunctional reagents have been synthesized that contain a new divalent disulfide-based protecting group. Amidation of HA with these reagents gives rise to either one-end coupling product or to intra/intermolecular cross-linking of the HA chains. However, after subsequent treatment of the amidation reaction mixture with dithiothreitol (DTT), these cross-linkages are cleaved, ultimately exposing free amine-type groups. The same methodology was applied to graft serine residues to the HA backbone, which were subsequently oxidized into aldehyde groups. The strategy therefore encompasses a new approach for mild and highly controlled functionalization of HA with both nucleophilic and electrophilic chemoselective functionalities with the emphasis for the subsequent conjugation and in situ cross-linking. A series of new hydrogel materials were prepared by mixing the new HA-aldehyde derivative with different HA-nucleophile counterparts. Rheological properties of the formed hydrogels were determined and related to the structural characteristics of the gel networks. Human dermal fibroblasts remained viable while cultured with the hydrogels for 3 days, with no sign of cytotoxicity, suggesting that the gels described in this study are candidates for use as growth factors delivery vehicles for tissue engineering applications.

  • 110.
    Ossipov, Dmitri A.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Yang, Xia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Varghese, Oommen
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Kootala, Sujit
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Modular approach to functional hyaluronic acid hydrogels using orthogonal chemical reactions2010Inngår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 46, nr 44, s. 8368-8370Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A modular approach for the synthesis of hyaluronic acid hydrogels using orthogonal chemoselective reactions for subsequent enzymatic decomposition to nanoparticles is described.

  • 111.
    Paidikondala, Maruthibabu
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Regulating Gene Expression to Promote Osteoblastic Differentiation of Stem Cells2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Bone is a tissue that heals by itself, unless the defect is too large (critical size). Today, novel regenerative medicine approaches have emerged as an alternative to treat such defects. This thesis explores alternative therapeutic strategies for bone tissue engineering which are biocompatible and clinically translatable. Many types of scaffolds that can act as reservoirs for growth factors such as rh-BMP-2 have been developed for bone tissue engineering in the past. However, the role of cross-linking chemistries that are employed to make hydrogels on the integrity and function of the loaded growth factors is not well understood. In this thesis, we have explored the influence of cross-linking chemistry on rh-BMP-2 integrity and bioactivity both in-vitro and in-vivo. These studies have demonstrated that thiol-Michael addition cross-linking chemistry greatly affects the integrity and bio-functionality of the loaded protein BMP-2 and leads to poor bone formation in an in-vivo rat model. On the other hand, hydrogels employing hydrazone chemistry did not significantly affect the integrity and bioactivity of BMP-2, which lead to a superior bone formation in-vivo. Since the high dose of rh-BMP-2 is known to confer many side effects, alternative ex-vivo strategies involving transient transfection of BMP-2 expressing plasmid DNA and silencing of anti-osteogenic genes using siRNA are developed. Our optimized method involves rapid transfection of hMSCs in suspension (5 minutes) with plasmid DNA followed by centrifugation and encapsulation in a hydrogel not only reduced cytotoxicity but also lead to efficient osteoblast differentiation of stem cells. Furthermore, this thesis presents the role of ECM-derived polymer HA in interacting with siRNA and trafficking across the plasma membrane, presumably through CD44 receptors and successfully silencing the target gene in-vitro. We explored the potential of such a non-cationic transfection method to deliver functional siRNA (anti-Pleckho-1 siRNA) in MSCs and compared it with commercially available cationic lipid LipofectamineTMRNAiMAX, using our optimized suspension transfection method. Our novel ex-vivo strategy employing HA hydrogels enabled efficient silencing of BMP-2 signaling pathway antagonist Pleckho-1 while avoiding the cytotoxicity issues in 3D, which further qualifies them for potential clinical application for cell-based therapies. 

    Delarbeid
    1. Rational Design of Biomaterials for Growth Factor Delivery: Impact of Hydrogel Crosslinking Chemistry on the In Vitroand In VivoBioactivity of Recombinant Human Bone Morphogenetic Protein-2
    Åpne denne publikasjonen i ny fane eller vindu >>Rational Design of Biomaterials for Growth Factor Delivery: Impact of Hydrogel Crosslinking Chemistry on the In Vitroand In VivoBioactivity of Recombinant Human Bone Morphogenetic Protein-2
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-369656 (URN)
    Tilgjengelig fra: 2018-12-14 Laget: 2018-12-14 Sist oppdatert: 2018-12-15
    2. Innovative strategy for 3D transfection of primary human stem cells with BMP-2 expressing plasmid DNA: A clinically translatable strategy for ex vivogene therapy
    Åpne denne publikasjonen i ny fane eller vindu >>Innovative strategy for 3D transfection of primary human stem cells with BMP-2 expressing plasmid DNA: A clinically translatable strategy for ex vivogene therapy
    2019 (engelsk)Inngår i: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, nr 1, artikkel-id 56Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Ex vivo gene therapy offers enormous potential for cell-based therapies, however, cumbersome in vitro cell culture conditions have limited its use in clinical practice. We have optimized an innovative strategy for the transient transfection of bone morphogenetic protein-2 (BMP-2) expressing plasmids in suspended human stem cells within 5-min that enables efficient loading of the transfected cells into a 3D hydrogel system. Such a short incubation time for lipid-based DNA nanoparticles (lipoplexes) reduces cytotoxicity and at the same time reduces the processing time for cells to be transplanted. The encapsulated human mesenchymal stromal/stem cells (hMSCs) transfected with BMP-2 plasmid demonstrated high expression of an osteogenic transcription factor, namely RUNX2, but not the chondrogenic factor (SOX9), within the first three days. This activation was also reflected in the 7-day and 21-day experiment, which clearly indicated the induction of osteogenesis but not chondrogenesis. We believe our transient transfection method demonstrated in primary MSCs can be adapted for other therapeutic genes for different cell-based therapeutic applications.

    sted, utgiver, år, opplag, sider
    Basel, Switzerland: MDPI, 2019
    Emneord
    hydrogel; DNA; transfection; ex vivo; hyaluronic acid
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-369655 (URN)10.3390/ijms20010056 (DOI)000459747700056 ()30583610 (PubMedID)
    Forskningsfinansiär
    EU, FP7, Seventh Framework Programme, FP7/2007-2013/607868Swedish Foundation for Strategic Research , SBE13-0028
    Tilgjengelig fra: 2018-12-14 Laget: 2018-12-14 Sist oppdatert: 2019-03-18bibliografisk kontrollert
    3. Hyaluronic acid facilitates non-cationic siRNA delivery and gene silencing in CD44 positive cells
    Åpne denne publikasjonen i ny fane eller vindu >>Hyaluronic acid facilitates non-cationic siRNA delivery and gene silencing in CD44 positive cells
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-369657 (URN)
    Tilgjengelig fra: 2018-12-14 Laget: 2018-12-14 Sist oppdatert: 2018-12-15
    4. New insight on siRNA transfection in three dimensions: Improved gene silencing in human mesenchymal stem cells encapsulated in hyaluronicacid hydrogel
    Åpne denne publikasjonen i ny fane eller vindu >>New insight on siRNA transfection in three dimensions: Improved gene silencing in human mesenchymal stem cells encapsulated in hyaluronicacid hydrogel
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-369658 (URN)
    Tilgjengelig fra: 2018-12-14 Laget: 2018-12-14 Sist oppdatert: 2018-12-15
  • 112.
    Paidikondala, Maruthibabu
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Nawale, Ganesh N.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Varghese, Oommen P.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Insights into siRNA Transfection in Suspension: Efficient Gene Silencing in Human Mesenchymal Stem Cells Encapsulated in Hyaluronic Acid Hydrogel2019Inngår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 20, nr 3, s. 1317-1324Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Small interfering RNAs (siRNAs) are powerful toolsfor post-transcriptional gene silencing, which offers enormousopportunities for tissue engineering applications. However, poorserum stability, inefficient intracellular delivery, and inevitabletoxicity of transfection reagents are the key barriers for their clinicaltranslation. Thus, innovative strategies that allow safe and efficientintracellular delivery of the nucleic acid drugs at the desired site isurgently needed for a smooth clinical translation of therapeuticallyappealing siRNA-based technology. In this regard, we havedeveloped an innovative siRNA transfection protocol that employsa short incubation time of just 5 min. This allows easy transfection insuspension followed by transplantation of the cells in a hyaluronicacid (HA) hydrogel system. We also report here the unique ability ofsiRNA to bind HA that was quantified by siRNA release andrheological characterization of the HA-hydrogel. Such interactions also showed promising results to deliver functional siRNA insuspension transfection conditions within 30 min using native HA, although removal of excess HA by centrifugation seem to beessential. In the 2D experiments, suspension transfection of hMSCs with RNAiMAX resulted in ≈90% gene silencing (with orwithout removal of the excess reagent by centrifugation), while HA demonstrated a modest ≈40% gene silencing after removalof excess reagent after 30 min. Transplantation of such transfected cells in the HA-hydrogel system demonstrated an improvedknockdown (≈90% and ≈60% with RNAiMAX and HA respectively after 48 h), with lower cytotoxicity (up to 5-days) asdetermined by PrestoBlue assay. The gene silencing efficiency in the 2D and 3D conditions were also confirmed at the proteinlevels by Western blot analysis. We postulate this novel transfection method could be applied for in vivo applications as it allowsminimal manipulation of cells that are to be transplanted and reduce toxicity.

  • 113.
    Paidikondala, Maruthibabu
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Wang, Shujiang
    Maisonneuve-Rosemont Hospital Research Centre & Department of Ophthalmology, University of Montreal.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Larsson, Sune
    Department of Surgical Sciences, Section of Orthopedics, Uppsala University Hospital.
    Varghese, Oommen P.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Impact of Hydrogel Cross-Linking Chemistry on the in Vitro and in VivoBioactivity of Recombinant Human Bone Morphogenetic Protein-22019Inngår i: ACS Applied Bio Materials, ISSN 2576-6422Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Designing strategies to deliver functional proteins at physiologically relevant concentrations using chemically cross-linked biocompatible hydrogels is a major field of research. However, the impact of cross-linking chemistry on the encapsulated protein bioactivity is rarely studied. Here we examine the two well-known cross-linking reactions namely; hydrazone cross-linking chemistry and thiol-Michael addition reaction to form hyaluronic acid (HA) hydrogels. As a therapeutic protein, we employed recombinant human bone morphogenetic protein-2 (rhBMP-2) for this study. Incubation of rhBMP-2 with HA functionalized with a thiol diminished phosphorylation of Smad 1/5/8, a signal transducer for osteogenic differntiation, whereas an aldehyde functionalized HA had no effect. This indicates that thiol functionalized polymers indeed has an impact on protein function. To validate this result in an in vivo setting we performed BMP-2 induced bone formation in a rat ectopic model. These experiments revealed that the hydrazone-cross-linked HA-hydrogel induced significantly higher bone formation (18.90 ± 4.25 mm3) as compared to the HA-thiol-Michael hydrogels (1.25 ± 0.52 mm3) after 8 weeks as determined by micro-computed tomography. The histological examination of the neo-bone indicated that hydrazone-hydrogels promoted a better quality of bone formation with improved mineralization and collagen formation as compared to the thiol-Michael hydrogels. We believe such a direct comparison of two cross-linking chemistries will provide new insight for developing biomaterials for protein delivery for in vivo applications.

  • 114.
    Pati, Palas Baran
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    Damas, Giane
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Tian, Lei
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    Fernandes, Daniel L. A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    Zhang, Lei
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    Bayrak Pehlivan, Ilknur
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Fasta tillståndets fysik.
    Edvinsson, Tomas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Fasta tillståndets fysik.
    Araujo, Carlos Moyses
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Tian, Haining
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Fysikalisk kemi.
    An experimental and theoretical study of an efficient polymer nano-photocatalyst for hydrogen evolution2017Inngår i: Energy & Environmental Science, ISSN 1754-5692, E-ISSN 1754-5706, Vol. 10, nr 6, s. 1372-1376Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this work, we report a highly efficient organic polymer nano-photocatalyst for light driven proton reduction. The system renders an initial rate of hydrogen evolution up to 50 +/- 0.5 mmol g(-1) h(-1), which is the fastest rate among all other reported organic photocatalysts. We also experimentally and theoretically prove that the nitrogen centre of the benzothiadiazole unit plays a crucial role in the photocatalysis and that the Pdots structure holds a close to ideal geometry to enhance the photocatalysis.

  • 115.
    Piskounova, Sonya
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Biomaterials for Promoting Self-Healing of Bone Tissue2011Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The present work addresses poor bone/implant integration and severe bone defects. In both conditions external stimuli is required for new bone to form. A multilayered functional implant coating, comprised of an inner layer of crystalline titanium dioxide (TiO2) and an outer layer of hydroxyapatite (HAP), loaded with bone morphogenetic protein-2 (BMP-2), was proposed as a tool for providing both improved initial bone formation and long-term osseointegration. The in vitro characterization of the implant coatings showed that TiO2 and HAP were more favorable for cell viability, cell morphology and initial cell differentiation, compared to native titanium oxide. Furthermore, significantly higher cell differentiation was observed on surfaces with BMP-2, indicating that a simple soaking process can be used for incorporating bioactive molecules. Moreover, the results suggest that there could be a direct interaction between BMP-2 and HAP, which prolongs the retention of the growth factor, improving its therapeutic effect.

    For treating severe bone defects a strategy involving BMP-2 delivery from hyaluronan hydrogels was explored. The hydrogels were prepared from two reactive polymers – an aldehyde-modified hyaluronan and a hydrazide-modified poly(vinyl alcohol). Upon mixing, the two components formed a chemically crosslinked hydrogel. In this work the mixing of the hydrogel components was optimized by rheological measurements. Furthermore, an appropriate buffer was selected for in vitro experiments by studying the swelling of hydrogels in PBS and in cell culture medium. A detection method, based on radioactive labeling of BMP-2 with 125I was used to monitor growth factor release both in vitro and in vivo. The results showed a biphasic release profile of BMP-2, where approximately 16 %  and 3 % of the growth factor remained inside the hydrogel after 4 weeks in vitro and in vivo, respectively. The initial fast release phase corresponded to the early ectopic bone formation observed 8 d after injection of the hydrogel formulation in the thigh muscle of rats. The hydrogel formulation could be improved by incorporation of HAP powder into the hydrogel formulation. Furthermore, bone formation could be increased by pre-incubation of the premixed hydrogel components inside the syringe prior to injection. Crushed hydrogels were also observed to induce more bone formation compared to solid hydrogels, when implanted subcutaneously in rats. This was thought to be due to increased surface area of the hydrogel, which allowed for improved cell infiltration.

    Delarbeid
    1. In vitro characterization of bioactive titanium dioxide/hydroxyapatite surfaces functionalized with BMP-2
    Åpne denne publikasjonen i ny fane eller vindu >>In vitro characterization of bioactive titanium dioxide/hydroxyapatite surfaces functionalized with BMP-2
    Vise andre…
    2009 (engelsk)Inngår i: Journal of biomedical materials research. Part B, Applied biomaterials, ISSN 1552-4981, Vol. 91B, nr 2, s. 780-787Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Poor implant fixation and bone resorption are two of the major challenges in modern orthopedics and are caused by poor bone/implant integration. In this work, bioactive crystalline titanium dioxide (TiO(2))/hydroxyapatite (HA) surfaces, functionalized with bone morphogenetic protein 2 (BMP-2), were evaluated as potential implant coatings for improved osseointegration. The outer layer consisted of HA, which is known to be osteoconductive, and may promote improved initial bone attachment when functionalized with active molecules such as BMP-2 in a soaking process. The inner layer of crystalline TiO(2) is bioactive and ensures long-term fixation of the implant, once the hydroxyapatite has been resorbed. The in vitro response of mesenchymal stem cells on bioactive crystalline TiO(2)/HA surfaces functionalized with BMP-2 was examined and compared with the cell behavior on nonfunctionalized HA layers, crystalline TiO(2) surfaces, and native titanium oxide surfaces. The crystalline TiO(2) and the HA surfaces showed to be more favorable than the native titanium oxide surface in terms of cell viability and cell morphology as well as initial cell differentiation. Furthermore, cell differentiation on BMP-2-functionalized HA surfaces was found to be significantly higher than on the other surfaces indicating that the simple soaking process can be used for incorporating active molecules, promoting fast bone osseointegration to HA layers.

    Emneord
    biomimetic hydroxyapatite, growth factors, BMP-2, anatase titanium dioxide, mesenchymal stem cells, differentiation, viability, morphology
    HSV kategori
    Forskningsprogram
    Teknisk fysik med inriktning mot nanoteknologi och funktionella material
    Identifikatorer
    urn:nbn:se:uu:diva-108680 (URN)10.1002/jbm.b.31456 (DOI)000270868600034 ()19582842 (PubMedID)
    Tilgjengelig fra: 2009-09-26 Laget: 2009-09-26 Sist oppdatert: 2018-02-08bibliografisk kontrollert
    2. The Effect of Mixing on the Mechanical Properties of Hyaluronan-Based Injectable Hydrogels
    Åpne denne publikasjonen i ny fane eller vindu >>The Effect of Mixing on the Mechanical Properties of Hyaluronan-Based Injectable Hydrogels
    2011 (engelsk)Inngår i: Macromolecular materials and engineering (Print), ISSN 1438-7492, E-ISSN 1439-2054, Vol. 296, nr 10, s. 944-951Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A method for determining the correlation between the mixing of two reactive polymers and the structural and mechanical properties of the formed hydrogels is presented. Rheological measurements show that insufficient mixing gives rise to soft and not fully crosslinked hydrogels while excessive mixing beyond gel point results in weaker hydrogels due to potential breakage of their 3D network. Furthermore, the hydrogels swell significantly more in cell culture medium than in phosphate-buffered saline, attributed to interactions with additional molecules such as proteins. Thus, moderate mixing gives rise to the most homogenous and mechanically stable hydrogels and the choice of medium e.g., for release experiments, should be consistent in order to avoid unnecessary variations in the data caused by different swelling profiles.

    Emneord
    Hydrogels, mixing, polymer, rheology, swelling
    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot polymerkemi
    Identifikatorer
    urn:nbn:se:uu:diva-158952 (URN)10.1002/mame.201100008 (DOI)000296421800008 ()
    Tilgjengelig fra: 2011-09-19 Laget: 2011-09-19 Sist oppdatert: 2017-12-08bibliografisk kontrollert
    3. Characterization of recombinant human bone morphogenetic protein-2 delivery from injectable hyaluronan-based hydrogels by means of I-125-radiolabelling
    Åpne denne publikasjonen i ny fane eller vindu >>Characterization of recombinant human bone morphogenetic protein-2 delivery from injectable hyaluronan-based hydrogels by means of I-125-radiolabelling
    Vise andre…
    2014 (engelsk)Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, nr 10, s. 821-830Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    This study presents a thorough in vitro and in vivo characterization of the delivery of bone morphogenetic protein 2 (BMP-2) from a hyaluronan-based hydrogel system. The in vitro release of BMP-2 from similar hydrogels has previously been studied by enzyme-linked immunosorbent assay (ELISA), by which only a fraction of the loaded protein is detected. In the current study, I-125 radiolabelling was used instead to monitor BMP-2 in vitro and in vivo. To minimize protein loss during handling, I-125-BMP-2 adsorption to different tubes was studied at different times and temperatures. The data showed that Protein LoBind tubes exhibited the lowest protein affinity. Furthermore, a biphasic release profile of biologically active BMP-2 was observed both in vitro and in vivo, with the initial fast phase during the first week, followed by a slower release during the remaining 3 weeks. The initial fast-release phase corresponded to the early bone formation observed after 8 days in an ectopic model in rats. Bone volume and mineral content increased until day 14, after which a decrease in bone volume was observed, possibly due to resorption in response to decreased amounts of released BMP-2. Overall, the results suggested that cautious protein handling and a reliable quantification technique are essential factors for successful design of a BMP-2 delivery system.

    Emneord
    BMP-2 delivery, radioactive labeling, hyaluronan hydrogels, reproducibility, ectopic bone formation, protein adsorption
    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot polymerkemi
    Identifikatorer
    urn:nbn:se:uu:diva-158961 (URN)10.1002/term.1584 (DOI)000343059700009 ()22927307 (PubMedID)
    Tilgjengelig fra: 2011-09-19 Laget: 2011-09-19 Sist oppdatert: 2018-12-04
    4. Pre-incubation of chemically crosslinked hyaluronan-based hydrogels, loaded with BMP-2 and hydroxyapatite, and its effect on ectopic bone formation
    Åpne denne publikasjonen i ny fane eller vindu >>Pre-incubation of chemically crosslinked hyaluronan-based hydrogels, loaded with BMP-2 and hydroxyapatite, and its effect on ectopic bone formation
    Vise andre…
    2014 (engelsk)Inngår i: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 25, nr 4, s. 1013-1023Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The effects of pre-incubation of hyaluronan hydrogels, for different lengths of time after the initiation of chemical crosslinking and prior to injection, were explored both by investigating the in vitro BMP-2 release kinetics from the hydrogel and by studying the ectopic bone formation in rats. From the curing profile, obtained from rheological analysis, appropriate pre-incubation times (1 min, 5 h and 3 days) were selected, to prepare slightly, moderately and fully cured hydrogels. Comparable release profiles were observed for all three test groups in vitro. Furthermore, radiography, pQCT and histology of the explanted grafts showed cancellous bone formation in all groups after 5 weeks in vivo. However, longer pre-incubation times gave rise to an increase in bone volume, but a decrease in bone density. Moreover, the 5 h and the 3 days grafts appeared to be more ordered and resistant to deformation from the surrounding tissue than the 1 min grafts. The observed variations in mechanical and biological properties could potentially be used to adapt the treatment for a specific indication.

    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot polymerkemi
    Identifikatorer
    urn:nbn:se:uu:diva-158963 (URN)10.1007/s10856-014-5147-y (DOI)000333093300006 ()
    Tilgjengelig fra: 2011-09-19 Laget: 2011-09-19 Sist oppdatert: 2018-12-04
    5. Improved bone formation through increased surface area of hyaluronan-based hydrogels when used as carriers for BMP-2
    Åpne denne publikasjonen i ny fane eller vindu >>Improved bone formation through increased surface area of hyaluronan-based hydrogels when used as carriers for BMP-2
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract
    Emneord
    Hyaluronan, hydroxyapatite, BMP, hydrogel, porosity, bone regeneration
    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot polymerkemi
    Identifikatorer
    urn:nbn:se:uu:diva-158967 (URN)
    Tilgjengelig fra: 2011-09-26 Laget: 2011-09-19 Sist oppdatert: 2018-09-13
  • 116.
    Piskounova, Sonya
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Gedda, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för biomedicinsk strålningsvetenskap.
    Hulsart Billström, Gry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Bowden, Tim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    The importance of proper protein handling and detection for the design of a BMP-2 release system2012Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, Vol. 6, nr s1, s. 322-322Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Although various promising strategies have been proposed for the delivery of BMP-2 for bone regeneration, there is currently no ideal system out on the market. Proper handling and detection of BMP-2 are two factors that are commonly overlooked, resulting in inaccurate characterization of BMP-2 delivery systems. In this work we employed radiolabeling with 125I in an attempt study the growth factor release from a hydrogel system both in vitro and in vivo. BMP-2 (InductOs, Pfizer) was radiolabeled using a modified chloramine-T method and adsorption to sample tubes was studied at different times and temperatures. In vitro release of BMP-2 was compared to the ALP expression. In vivo release was correlated to bone formation in an intramuscular ectopic model in male Sprague–Dawley rats. The results showed that Protein LoBind tubes exhibited the lowest BMP-2 adsorption. Both release studies resulted in a biphasic profile of biologically active BMP-2. Mineralization was observed in vivo after 8 days, with increasing mineral volume and mineral content until day 14. The study confirmed the superiority of radiolabeling over conventional methods such as ELISA, as well as the importance of cautions handling and reliable quantification techniques for successful design of BMP-2 delivery systems

  • 117.
    Piskounova, Sonya
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Rojas, Ramiro
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Bergman, Kristoffer
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    The Effect of Mixing on the Mechanical Properties of Hyaluronan-Based Injectable Hydrogels2011Inngår i: Macromolecular materials and engineering (Print), ISSN 1438-7492, E-ISSN 1439-2054, Vol. 296, nr 10, s. 944-951Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A method for determining the correlation between the mixing of two reactive polymers and the structural and mechanical properties of the formed hydrogels is presented. Rheological measurements show that insufficient mixing gives rise to soft and not fully crosslinked hydrogels while excessive mixing beyond gel point results in weaker hydrogels due to potential breakage of their 3D network. Furthermore, the hydrogels swell significantly more in cell culture medium than in phosphate-buffered saline, attributed to interactions with additional molecules such as proteins. Thus, moderate mixing gives rise to the most homogenous and mechanically stable hydrogels and the choice of medium e.g., for release experiments, should be consistent in order to avoid unnecessary variations in the data caused by different swelling profiles.

  • 118.
    Podiyan, Oommen
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Garousi, Javad
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Sloff, Marije
    Varghese, Oommen
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Tailored Doxorubicin-Hyaluronan Conjugate as a Potent Anticancer Glyco-Drug: An Alternative to Prodrug Approach2014Inngår i: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 14, nr 3, s. 327-333Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Releasibility of doxorubicin from drug-conjugates is believed to be a prerequisite for its anti- cancer activity. Here, a new glyco-drug approach that circumvents the releasibility restriction is reported, opening a new possibility to design efficient, target specific drug delivery system. It is discovered that stable amide coupling of doxorubicin (DOX) tohyaluronan (HA) shows dose dependent cytotoxicity to CD44 positive human coloncancer cells (HCT116) as compared to human breast cancer cells(MCF-7) and mouse fibroblast cells (NIH-3T3), which express less CD44 receptor. This direct conjugation approach is an easy scalable strategy that could be adopted to design innocuous anti-tumor nanoparticle formulations.

  • 119.
    Podiyan, Oommen
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Wang, Shujiang
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Kisiel, Marta
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Varghese, Oommen P.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Smart design of stable hydrazone crosslinked extracellular matrix mimetic hydrogel for tissue engineering application2012Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, Vol. 6, nr suppl 1, s. 192-192Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Injectable hydrogels are important biomaterials with enormous applications. They are used for various biomedical applications such as diagnostics, 3D cell culture matrix, drug reservoir, encapsulation of bioactive compounds and growth factors, scaffold for tissue engineering etc. We here present our recent development in our efforts to develop hydrogel scaffolds with enhanced rigidity, stability, swelling characteristics. Hydrazone crosslinked gels are attractive due to its simplicity and versatility which could be formed by mixing appropriate aldehyde and hydrazide functionalized hyaluronan. By fine-tuning the electronic character around the hydrazone linkage, we succeeded in developing extremely stable hydrazone bond and utilized it for developing hyaluronan (HA) based synthetic extracellular matrix (ECM) hydrogel. Among the different hydrazides tested, we identified carbonyldihydrazide (CDH) as the best candidate to deliver stable hydrazone linkage. This stability is presumably due to extensive delocalization of the positive charge across neighboring amino groups of CDH. The hydrolytic stability imparted by this group was found to be several folds under acidic, basic and physiological pH when compared to other hydrazones. This tailored hydrogel with CDH also exhibited superior swelling and mechanical properties and enzymatic stability which makes it ideal for tissue engineering application.

  • 120.
    Quinones, Javier Perez
    et al.
    Johannes Kepler Univ Linz, Inst Polymer Chem, Altenberger Str 69, A-4040 Linz, Austria..
    Jokinen, Johanna
    Univ Turku, Dept Biochem, Vatselankatu 2, SF-20500 Turku, Finland..
    Keinanen, Salli
    Univ Turku, Dept Biochem, Vatselankatu 2, SF-20500 Turku, Finland..
    Covas, Carlos Peniche
    Univ Havana, Ctr Biomat, Ave Univ S-N Entre G & Ronda, Havana 10400, Cuba..
    Brueggemann, Oliver
    Johannes Kepler Univ Linz, Inst Polymer Chem, Altenberger Str 69, A-4040 Linz, Austria..
    Ossipov, Dmitri
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Self-assembled hyaluronic acid-testosterone nanocarriers for delivery of anticancer drugs2018Inngår i: European Polymer Journal, ISSN 0014-3057, E-ISSN 1873-1945, Vol. 99, s. 384-393Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The present research aims at controlled delivery of anticancer drugs camptothecin and doxorubicin through encapsulation in self-assembled hyaluronic acid (HA)-testosterone conjugates. The conjugates were obtained by functionalization of either natural sodium hyaluronate or hydrazide-modified HA derivatives with testosterone hemisuccinate. From 2.0 to 7.7% of HA disaccharide units were linked to testosterone via two types of linkers of different length. Fourier transform infrared and proton nuclear magnetic resonance spectroscopies confirmed modification of HA. Conjugation of hydrophobic testosterone to hydrophilic backbone of HA resulted in the self assembly of amphiphilic HA-testosterone conjugates in aqueous medium and the formation of stable and negatively charged nanoparticles with hydrodynamic diameter ranging from 172 to 380 nm and.-potential ranging from - 37 to - 26 mV, as evidenced from dynamic light scattering measurements. Examination of the dried conjugates by transmission electron microscopy revealed almost spherical particles of 50-100 nm size. Entrapment of camptothecin and doxorubicin in the hydrophobic core of HA -testosterone nanoparticles was performed with the drugs content of ca. 2.8 wt% and 3.5 wt% respectively. The sustained release of the anticancer drugs over 96 h was observed in phosphate buffered saline at pH 7.4. Cytotoxicity of camptothecin- and doxorubicin-loaded HA -testosterone nanoparticles against MCF-7 cancer cell line was found to be similar to the cytotoxicity of the free anticancer drugs. Based on the results of the in vitro studies, we can conclude that the developed HA -testosterone nanoparticles are promising candidates in chemotherapy treatments of cancers.

  • 121.
    Quinones, Javier Pérez
    et al.
    Johannes Kepler Univ Linz, Inst Polymer Chem..
    Bruggemann, Oliver
    Johannes Kepler Univ Linz, Inst Polymer Chem..
    Covas, Carlos Peniche
    Univ Havana, Ctr Biomat..
    Ossipov, Dmitri A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Self-assembled hyaluronic acid nanoparticles for controlled release of agrochemicals and diosgenin2017Inngår i: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 173, s. 157-169Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Commercial sodium hyaluronate (HA) and synthetic hydrazide-modified HA were functionalized with diosgenin and two agrochemicals (brassinosteroids DI31 and S7) with degree of substitution ranging from 5.6 to 13.1%. The HA-steroid conjugates were studied with FTIR, H-1 NMR and differential scanning calorimetry. Dynamic light scattering revealed self-assembly of the HA-steroid conjugates into stable negatively charged nanoparticles of around 159 nm-441 nm in water, which after drying appeared as 140 nm-370 nm spherically shaped nanoparticles according to transmission electron microscopy. These nanoparticles exhibited almost constant release rates of steroids for the first 8 h, demonstrating sustained steroids delivery for 72 h in acidic medium. The nanoparticles formed from HA-steroid conjugates were not cytotoxic to human microvascular endothelial cells (HMVEC), while the HA- brassinosteroid nanoparticles showed in vitro agrochemical activity that was superior to the activity observed for the parent brassinosteroids DI31 and S7 at 10(-5) to 10(-7) mg mL(-1).

  • 122.
    Rahman, M.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Elektricitetslära och åskforskning.
    Thottappillil, R.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Elektricitetslära och åskforskning.
    Berg, M.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Elektricitetslära och åskforskning.
    Hillborg, H.
    Surface Charge and Hydrophobicity Levels of Insulating Materials2001Inngår i: 12th Int. Symp. on High Voltage Engineering, ISH-2001, Bangalore, India, August 20-24, p628-631,, 2001, s. 628-631Konferansepaper (Fagfellevurdert)
  • 123.
    Rahman, Mahbubur
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Elektricitetslära och åskforskning.
    Thottappillil, R.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Elektricitetslära och åskforskning.
    Berg, M.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Elektricitetslära och åskforskning.
    Hillborg, H.
    Comment on 'Effect of surface charge on hydrophobicity levels of insulating materials'2002Inngår i: IEE Proceedings - Generation Transmission and Distribution, ISSN 1350-2360, E-ISSN 1359-7051, Vol. 149, nr 3, s. 300-304Artikkel i tidsskrift (Fagfellevurdert)
  • 124.
    Ranga, Adrian
    et al.
    Ecole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, Lab Stem Cell Bioengn, CH-1015 Lausanne, Switzerland.;Ecole Polytech Fed Lausanne, Sch Engn, CH-1015 Lausanne, Switzerland.;Katholieke Univ Leuven, Dept Mech Engn, Biomech Sect, Celestijnenlaan 300, B-3001 Leuven, Belgium..
    Lutolf, Matthias P.
    Ecole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, Lab Stem Cell Bioengn, CH-1015 Lausanne, Switzerland.;Ecole Polytech Fed Lausanne, Sch Engn, CH-1015 Lausanne, Switzerland.;Ecole Polytech Fed Lausanne, Sch Basic Sci, Inst Chem Sci & Engn, CH-1015 Lausanne, Switzerland..
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Ossipov, Dmitri A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Hyaluronic Acid Hydrogels Formed in Situ by Transglutaminase-Catalyzed Reaction2016Inngår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 17, nr 5, s. 1553-1560Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Enzymatically cross-linked hydrogels can be formed in situ and permit highly versatile and selective tethering of bioactive molecules, thereby allowing for a wealth of applications in cell biology and tissue engineering. While a number of studies have reported the bioconjugation of extracellular matrix (ECM) proteins and peptides into such matrices, the site specific incorporation of biologically highly relevant polysaccharides such as hyaluronic acid (HA) has thus far not been reported, limiting our ability to reconstruct this key feature of the in vivo ECM. Here we demonstrate a novel strategy for transglutaminase-mediated covalent linking of HA moieties to a synthetic poly(ethylene glycol) (PEG) macromer resulting in the formation of hybrid HA-PEG hydrogels. We characterize the ensuing matrix properties and demonstrate how these cytocompatible gels can serve to modulate the cellular phenotype of human mammary cancer epithelial cells as well as mouse myoblasts. The use of HA as a novel building block in the increasingly varied library of synthetic PEG-based artificial ECMs should have applications as a structural as well as a signaling component and offers significant potential as an injectable matrix for regenerative medicine.

  • 125.
    Ravichandran, R.
    et al.
    Linkoping Univ, Integrat Regenerat Med Ctr IGEN, S-58183 Linkoping, Sweden.;Linkoping Univ, Dept Phys Chem & Biol IFM, Div Mol Phys, S-58183 Linkoping, Sweden..
    Islam, M. M.
    Karolinska Inst, Integrat Regenerat Med Ctr IGEN, S-17177 Stockholm, Sweden.;Karolinska Inst, Swedish Med Nanosci Ctr, Dept Neurosci, S-17177 Stockholm, Sweden..
    Alarcon, E. I.
    Univ Ottawa, Inst Heart, Div Cardiac Surg Res, Ottawa, ON, Canada.;Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada..
    Samanta, Ayan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Linkoping Univ, Integrat Regenerat Med Ctr, S-58185 Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med IKE, S-58185 Linkoping, Sweden..
    Wang, Shujiang
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Lundstrom, P.
    Linkoping Univ, Dept Phys Chem & Biol IFM, Div Chem, S-58183 Linkoping, Sweden..
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Griffith, M.
    Linkoping Univ, Integrat Regenerat Med Ctr, S-58185 Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med IKE, S-58185 Linkoping, Sweden..
    Phopase, J.
    Linkoping Univ, Integrat Regenerat Med Ctr IGEN, S-58183 Linkoping, Sweden.;Linkoping Univ, Dept Phys Chem & Biol IFM, Div Mol Phys, S-58183 Linkoping, Sweden..
    Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications2016Inngår i: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 4, nr 2, s. 318-326Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this study, we derivatized type I collagen without altering its triple helical conformation to allow for facile hydrogel formation via the Michael addition of thiols to methacrylates without the addition of other crosslinking agents. This method provides the flexibility needed for the fabrication of injectable hydrogels or pre-fabricated implantable scaffolds, using the same components by tuning the modulus from Pa to kPa. Enzymatic degradability of the hydrogels can also be easily fine-tuned by variation of the ratio and the type of the crosslinking component. The structural morphology reveals a lamellar structure mimicking native collagen fibrils. The versatility of this material is demonstrated by its use as a pre-fabricated substrate for culturing human corneal epithelial cells and as an injectable hydrogel for 3-D encapsulation of cardiac progenitor cells.

  • 126.
    Rognås, Viktor
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Stenberg, Hanna
    Customer Based Business Development: Strategic Challenges for a Small Research-Based Spin-Off Enterprise2017Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    The biotechnology industry is one of the fastest growing sectors of the western economy. The biotech industry is helping the world by creating significant societal and economic value in various sectors. However, as a result of the fast development of the biotech industry, the environment is constantly changing and doing so at a high pace. Hence, biotech companies are forced to always stay competitive and improve their business in order not to be outrivaled.

    XYZ is a family-owned chemical company based in Europe. The company’s main business is polysaccharide chemistry but specializes in fluorescent dextran derivatives for which XYZ offer different goods and services. Dextran is a polysaccharide that has been widely used as a research tool in various scientific fields. XYZ has been struggling with stagnating sales and wants to grow their business and find new customers.

    The purpose of this master thesis is to suggest ways of business development for XYZ through customer and market understanding. Assessment of the company’s current strategy, market and customers will aid in understanding the company’s value proposition and identify opportunities for business development. Data were collected mainly through qualitative unstructured interviews.

    In conclusion, based on the empirical results we recommend to assess the value propositions that the company is currently offering to customers. This should be done before reaching out to new customers. Further, this project aims to describe the factors a small research-based enterprise should consider when designing a business strategy.

  • 127. Rundlöf, Torgny
    et al.
    Mathiasson, Marie
    Bekiroglu, Somer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för analytisk farmaceutisk kemi.
    Hakkarainen, Birgit
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för analytisk farmaceutisk kemi.
    Bowden, Tim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Arvidsson, Torbjörn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för analytisk farmaceutisk kemi.
    Survey and qualification of internal standards for quantification by 1H NMR spectroscopy2010Inngår i: Journal of Pharmaceutical and Biomedical Analysis, ISSN 0731-7085, E-ISSN 1873-264X, Vol. 52, nr 5, s. 645-651Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In quantitative NMR (qNMR) selection of an appropriate internal standard proves to be crucial. In this study, 25 candidate compounds considered to be potent internal standards were investigated with respect to the ability of providing unique signal chemical shifts, purity, solubility, and ease of use. The 1H chemical shift (δ) values, assignments, multiplicities and number of protons (for each signal), appropriateness (as to be used as internal standards) in four different deuterated solvents (D2O, DMSO-d6, CD3OD, CDCl3) were studied. Taking into account the properties of these 25 internal standards, the most versatile eight compounds (2,4,6-triiodophenol, 1,3,5-trichloro-2-nitrobenzene, 3,4,5-trichloropyridine, dimethyl terephthalate, 1,4-dinitrobenzene, 2,3,5-triiodobenzoic acid, maleic acid and fumaric acid) were qualified using both differential scanning calorimetry (DSC) and NMR spectroscopy employing highly pure acetanilide as the reference standard. The data from these two methods were compared as well as utilized in the quality assessment of the compounds as internal standards. Finally, the selected internal standards were tested and evaluated in a real case of quantitative NMR analysis of a paracetamol pharmaceutical product.

  • 128. Saxena, Shalini
    et al.
    Ray, Alok R.
    Mindemark, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Gupta, Bhuvanesh
    Plasma-Induced Graft Polymerization of Acrylic Acid onto Poly(propylene) Monofilament: Characterization2010Inngår i: Plasma Processes and Polymers, ISSN 1612-8850, Vol. 7, nr 7, s. 610-618Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Poly(propylene) (PP) filaments were functionalized by plasma-grafting of acrylic acid and the characterization of the grafted filaments was carried out using various techniques. XPS content which causes a decrease in the analysis showed an increase in the oxygenated contact angle decreased from 88 for virgin PP to 28 for the filament with the maximum graft level. The storage of the samples leads to the loss in hydrophilicity. The grafts do not lead to any crystalline changes in the filament structure; significant changes however occur on the surface of the filaments as a function of the degree of grafting.

  • 129.
    Schwartz, Pierre-Olivier
    et al.
    Alsachim SAS, Strasbourg, France;Ulm Univ, Inst Organ Chem & Adv Mat 2, Albert Einstein Allee 11, D-89081 Ulm, Germany.
    Pejic, Marijana
    ZSW Zentrum Sonnenenergie & Wasserstoff Forsch Ba, Helmholtzstr 8, D-89081 Ulm, Germany.
    Wachtler, Mario
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi. ZSW Zentrum Sonnenenergie & Wasserstoff Forsch Ba, Helmholtzstr 8, D-89081 Ulm, Germany.
    Baeuerle, Peter
    Ulm Univ, Inst Organ Chem & Adv Mat 2, Albert Einstein Allee 11, D-89081 Ulm, Germany.
    Synthesis and characterization of electroactive PEDOT-TEMPO polymers as potential cathode materials in rechargeable batteries2018Inngår i: Synthetic metals, ISSN 0379-6779, E-ISSN 1879-3290, Vol. 243, s. 51-57Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Herein we report a novel series of conjugated polymers bearing stable nitroxide pendant groups for possible applications as cathode-active material in secondary batteries. The polymers comprise a 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) moiety immobilized on a poly(3,4-ethylenedioxythiophene) (PEDOT) backbone via ester groups (PEDOT-TEMPO P1 and PEDOT-diTEMPO P2). The multistep synthesis of the corresponding monomers and their chemical characterization are described. Furthermore, oxidative electrochemical and chemical polymerization were performed in order to synthesize polymers on gram-scale for battery tests and to investigate their electrochemical behaviour, respectively. In addition, the electrochemical properties of polymer P1 were studied by potentiodynamic and galvanostatic methods. The results demonstrate that the as-synthesized nitroxide radical polymers showed an electrochemically reversible redox reaction of the TEMPO radicals at 3.5 V vs Li/Li+. When used as cathode material in galvanostatic cycling tests, P1 exhibited a moderate initial specific capacity of 47 mA h g(-1) (62% of the theoretical capacity) which slowly fades to 38 mA h within 50 cycles.

  • 130.
    Shakari, Patrick
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Irreversible strengthening of gelatin hydrogels by salt-directed polypeptide assembly and covalent crosslinking2019Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Fulltekst tilgjengelig fra 2021-06-05 19:28
  • 131.
    Shi, Liyang
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Injectable Composite Hydrogels Based on Metal-Ligand Assembly for Biomedical Applications2018Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis presents new strategies to construct injectable hydrogels and their various biomedical applications, such as 3D printing, regenerative medicine and drug delivery. These hydrogels cross-linked by dynamic metal-ligand coordination bonds exhibit shear-thinning and self-healing properties, resulting in the unlimited time window for injection. Compared with non-dynamic networks based on chemically reactive liquid polymer precursors that forms covalent bond during and/or post-injection, our injectable hydrogels with dynamic cross-linkages can be injected from an already cross-linked hydrogel state. 

    Hyaluronic acid (HA) has been selected as the polymer due to its high biocompatibility and biodegradability. HA has been modified by attaching the bisphosphonates (BP) functionality as ligands for chelation of the metal ions or metal salts to form coordination cross-linkages. In the first part of this thesis, I presented the different chemical approaches to synthesize BP-modified HA (HA-BP) derivatives as well as HA derivatives dually modified with BP and acrylamide (Am) groups (Am-HA-BP). The structures of HA-BP derivatives were confirmed by NMR characterizations, e.g. by the peak at 2.18 ppm for methylene protons adjacent to the bridging carbon of BP in 1H-NMR spectrum and phosphorus peak at 18.27 ppm in 31P-NMR spectrum, respectively. In the next part, the hydrogels were constructed by simple mixing of HA-BP or Am-HA-BP solution with Ca2+ ions (Paper I), Ag+ ions (Paper II),  calcium phosphonate coated silk microfibers (CaP@mSF) (Paper III), and magnesium silicate (MgSiO3) nanoparticles (Paper IV). The presented hydrogels exhibited dynamic features determined by reversible nature of coordination networks formed between of BP moieties of HA-BP or Am-HA-BP and metal ions or metal salts on the surface of the inorganic particles. Dynamic properties were characterized by rheological strain sweep experiments and strain-alternating time sweep experiments. Additionally, reversible coordination hydrogels were demonstrated to be further covalently cross-linked by UV light to form a secondary cross-linkage, allowing an increase of the strength and modulus of the hydrogels. In the last part of this thesis, biomedical applications of these hydrogels were presented. Am-HA-BP•Ca2+ hydrogel was extruded, using home-made 3D printer, then fixed by UV irradiation to fabricate multi-layered 3D tube-like construct (Paper I). In full-thickness skin defects of rat model, HA-BP•Ag+ hydrogel accelerated the wound healing process and increased thickness of newly-regenerated epidermal layer (Paper II). In the rat cranial critical defect model, double cross-linked Am-HA-BP•CaP@mSF hydrogel induced new bone formation without addition of biological factors and cells (Paper III). The anti-cancer drug loaded hydrogel was also prepared by mixing of the drug loaded MgSiO3 nanoparticles with HA-BP solution. The released particles from the hydrogel were shown to be taken up by cancer cells to induce a toxic response (Paper IV).

    In summary, this thesis presents metal-ligand coordination chemical strategies to build injectable hydrogels with dynamic cross-linking resulting in time-independent injection behavior. These hydrogels open new possibilities for use in biomedical areas.

    Delarbeid
    1. Dynamic Coordination Chemistry Enables Free Directional Printing of Biopolymer Hydrogel
    Åpne denne publikasjonen i ny fane eller vindu >>Dynamic Coordination Chemistry Enables Free Directional Printing of Biopolymer Hydrogel
    Vise andre…
    2017 (engelsk)Inngår i: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 29, s. 5816-5823Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Three-dimensional (3D) printing is a promising technology to develop customized biomaterials in regenerative medicine. However, for the majority of printable biomaterials (bioinks) there is always a compromise between excellent printability of fluids and good mechanical properties of solids. 3D printing of soft materials based on the transition from a fluid to gel state is challenging because of the difficulties to control such transition as well as to maintain uniform conditions three-dimensionally. To solve these challenges, a facile chemical strategy for the development of a novel hydrogel bioink with shear-thinning and self-healing properties based on dynamic metal-ligand coordination bonds is presented. The non-covalent cross-linking allows easy extrusion of the bioink from a reservoir without changing of its bulk mechanical properties. The soft hydrogel can avoid deformation and collapse using omnidirectional embedding of the printable hydrogel into a support gel bath sharing the same cross-linking chemistry. After combination with photo-initiated covalent cross-linking, it enables manufacturing of hydrogel structures with complex shapes and precise location of chemically attached ligands. Living cells can be entrapped in the new printable hydrogel and survive the following in situ photocross-linking. The presented printable hydrogel mate-rial expands the existing tool-box of bioinks for generation of in vitro 3D tissue-like structures and direct in vivo 3D printing.

    sted, utgiver, år, opplag, sider
    American Chemical Society (ACS), 2017
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-324796 (URN)10.1021/acs.chemmater.7b00128 (DOI)000406573200011 ()
    Forskningsfinansiär
    EU, European Research Council, 307701
    Tilgjengelig fra: 2017-06-19 Laget: 2017-06-19 Sist oppdatert: 2018-09-03bibliografisk kontrollert
    2. Moldable Hyaluronan Hydrogel Enabled by Dynamic Metal–Bisphosphonate Coordination Chemistry for Wound Healing
    Åpne denne publikasjonen i ny fane eller vindu >>Moldable Hyaluronan Hydrogel Enabled by Dynamic Metal–Bisphosphonate Coordination Chemistry for Wound Healing
    Vise andre…
    2018 (engelsk)Inngår i: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 7, nr 5, artikkel-id 1700973Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Biomaterial-based regenerative approaches would allow for cost-effective off-the-shelf solution for the treatment of wounds. Hyaluronan (HA)-based hydrogel is one attractive biomaterial candidate because it is involved in natural healing processes, including inflammation, granulation, and reepi-thelialization. Herein, dynamic metal–ligand coordination bonds are used to fabricate moldable supramolecular HA hydrogels with self-healing properties. To achieve reversible crosslinking of HA chains, the biopolymer is modified with pendant bisphosphonate (BP) ligands using carbodiimide coupling and chemoselective “click” reactions. Hydrogel is formed immediately after simple addition of silver (Ag+) ions to the solution of HA containing BP groups (HA-BP). Compared with previous HA-based wound healing hydrogels, the HA-BP·Ag+ hydrogel is highly suitable for clinical use as it can fill irregularly shaped wound defects without the need for premolding. The HA-BP·Ag+ hydrogel shows antimicrobial properties to both Gram-positive and Gram-negative bacterial strains, enabling prevention of infections in wound care. In vivo evaluation using a rat full-thickness skin wound model shows sig-nificantly lower wound remaining rate and a thicker layer of regenerated epidermis as compared with the group left without treatment. The presented moldable and self-healing supramolecular HA hydrogel with “ready-to-use” properties possesses a great potential for regenerative wound treatment.

    Emneord
    antibacterial, bisphosphonate, hyaluronan, moldable, wound healing
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-338080 (URN)10.1002/adhm.201700973 (DOI)000426758500016 ()
    Tilgjengelig fra: 2018-01-07 Laget: 2018-01-07 Sist oppdatert: 2018-06-27bibliografisk kontrollert
    3. Self-Healing Silk Fibroin-Based Hydrogel for Bone Regeneration: Dynamic Metal-Ligand Self-Assembly Approach
    Åpne denne publikasjonen i ny fane eller vindu >>Self-Healing Silk Fibroin-Based Hydrogel for Bone Regeneration: Dynamic Metal-Ligand Self-Assembly Approach
    Vise andre…
    2017 (engelsk)Inngår i: Advanced Functional Materials, artikkel-id 1700591Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Despite advances in the development of silk fibroin (SF)-based hydrogels, current methods for SF gelation show significant limitations such as lack of reversible crosslinking, use of nonphysiological conditions, and difficulties in controlling gelation time. In the present study, a strategy based on dynamic metal-ligand coordination chemistry is developed to assemble SF-based hydrogel under physiological conditions between SF microfibers (mSF) and a polysaccharide binder. The presented SF-based hydrogel exhibits shear-thinning and autonomous self-healing properties, thereby enabling the filling of irregularly shaped tissue defects without gel fragmentation. A biomineralization approach is used to generate calcium phosphate-coated mSF, which is chelated by bisphosphonate ligands of the binder to form reversible crosslinkages. Robust dually crosslinked (DC) hydrogel is obtained through photopolymerization of acrylamide groups of the binder. DC SF-based hydrogel supports stem cell proliferation in vitro and accelerates bone regeneration in cranial critical size defects without any additional morphogenes delivered. The developed self-healing and photopolymerizable SF-based hydrogel possesses significant potential for bone regeneration application with the advantages of injectability and fit-to-shape molding.

    Emneord
    bone regeneration, hydrogels, self-assembly, self-healing, silk fibroin
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-327126 (URN)10.1002/adfm.201700591 (DOI)000412324200012 ()
    Forskningsfinansiär
    EU, FP7, Seventh Framework Programme
    Tilgjengelig fra: 2017-08-04 Laget: 2017-08-04 Sist oppdatert: 2018-06-27bibliografisk kontrollert
    4. “Smart” drug loaded nanoparticle delivery from a self-healing hydrogel enabled by dynamic magnesium–biopolymer chemistry
    Åpne denne publikasjonen i ny fane eller vindu >>“Smart” drug loaded nanoparticle delivery from a self-healing hydrogel enabled by dynamic magnesium–biopolymer chemistry
    2016 (engelsk)Inngår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 52, nr 74, s. 11151-11154Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    We report a strategy to generate a self-healing and pH responsive hydrogel network between drug-loaded nanoparticles and natural polysaccharides via magnesium–bisphosphonate ligand interactions. The injectable drug depot disassembles in a tumor-specific environment, providing localized uptake of the nanoparticles, which is highly appreciated in drug delivery applications and manufacturing of drug-loaded biomaterials using a syringe-based deposition technique.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-301659 (URN)10.1039/C6CC05565F (DOI)000384202000027 ()27550535 (PubMedID)
    Tilgjengelig fra: 2016-08-24 Laget: 2016-08-24 Sist oppdatert: 2019-04-24bibliografisk kontrollert
  • 132.
    Shi, Liyang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Carstensen, Hauke
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik.
    Hölzl, Katja
    Institute of Materials Science and Technology, Technische Universität Wien.
    Lunzer, Markus
    Institute of Materials Science and Technology, Technische Universität Wien.
    Li, Hao
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Ovsianikov, Aleksandr
    Institute of Materials Science and Technology, Technische Universität Wien.
    Ossipov, Dmitri A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Dynamic Coordination Chemistry Enables Free Directional Printing of Biopolymer Hydrogel2017Inngår i: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 29, s. 5816-5823Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Three-dimensional (3D) printing is a promising technology to develop customized biomaterials in regenerative medicine. However, for the majority of printable biomaterials (bioinks) there is always a compromise between excellent printability of fluids and good mechanical properties of solids. 3D printing of soft materials based on the transition from a fluid to gel state is challenging because of the difficulties to control such transition as well as to maintain uniform conditions three-dimensionally. To solve these challenges, a facile chemical strategy for the development of a novel hydrogel bioink with shear-thinning and self-healing properties based on dynamic metal-ligand coordination bonds is presented. The non-covalent cross-linking allows easy extrusion of the bioink from a reservoir without changing of its bulk mechanical properties. The soft hydrogel can avoid deformation and collapse using omnidirectional embedding of the printable hydrogel into a support gel bath sharing the same cross-linking chemistry. After combination with photo-initiated covalent cross-linking, it enables manufacturing of hydrogel structures with complex shapes and precise location of chemically attached ligands. Living cells can be entrapped in the new printable hydrogel and survive the following in situ photocross-linking. The presented printable hydrogel mate-rial expands the existing tool-box of bioinks for generation of in vitro 3D tissue-like structures and direct in vivo 3D printing.

  • 133.
    Shi, Liyang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Hunan Univ, Coll Biol, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China.
    Ding, Pinghui
    Hunan Univ, Coll Biol, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China.
    Wang, Yuzhi
    Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China.
    Zhang, Yu
    Northwest Univ, Coll Chem & Mat Sci, Xian 710069, Shaanxi, Peoples R China.
    Ossipov, Dmitri
    Karolinska Inst, Dept Biosci & Nutr, Hasovagen 7c, S-14157 Huddinge, Sweden.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Self-Healing Polymeric Hydrogel Formed by Metal-Ligand Coordination Assembly: Design, Fabrication, and Biomedical Applications2019Inngår i: Macromolecular rapid communications, ISSN 1022-1336, E-ISSN 1521-3927, Vol. 40, nr 7, artikkel-id 1800837Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Self-healing hydrogels based on metal-ligand coordination chemistry provide new and exciting properties that improve injectability, rheological behaviors, and even biological functionalities. The inherent reversibility of coordination bonds improves on the covalent cross-linking employed previously, allowing for the preparation of completely self-healing hydrogels. In this article, recent advances in the development of this class of hydrogels are summarized and their applications in biology and medicine are discussed. Various chelating ligands such as bisphosphonate, catechol, histidine, thiolate, carboxylate, pyridines (including bipyridine and terpyridine), and iminodiacetate conjugated onto polymeric backbones, as well as the chelated metal ions and metal ions containing inorganic particles, which are used to form dynamic networks, are highlighted. This article provides general ideas and methods for the design of self-healing hydrogel biomaterials based on coordination chemistry.

  • 134.
    Shi, Liyang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Han, Yuanyuan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Ossipov, Dmitri
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    “Smart” drug loaded nanoparticle delivery from a self-healing hydrogel enabled by dynamic magnesium–biopolymer chemistry2016Inngår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 52, nr 74, s. 11151-11154Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We report a strategy to generate a self-healing and pH responsive hydrogel network between drug-loaded nanoparticles and natural polysaccharides via magnesium–bisphosphonate ligand interactions. The injectable drug depot disassembles in a tumor-specific environment, providing localized uptake of the nanoparticles, which is highly appreciated in drug delivery applications and manufacturing of drug-loaded biomaterials using a syringe-based deposition technique.

  • 135.
    Shi, Liyang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Ossipov, Dmitri
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Bisphosphonate-functionalized hyaluronic acid hydrogel as three-dimensional printable bioink2016Konferansepaper (Fagfellevurdert)
  • 136.
    Shi, Liyang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Wang, Fanlu
    Experimental Trauma Surgery, University Medical Center Schleswig Holstein UKSH, Kiel, Germany.
    Zhu, Wei
    Department of Big Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
    Xu, Zongpu
    Institute of Applied Bioresources Research, College of Animal Science, Zhejiang University, Hangzhou, China.
    Fuchs, Sabine
    Experimental Trauma Surgery, University Medical Center Schleswig Holstein UKSH, Kiel, Germany.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Zhu, Liangjun
    Institute of Applied Bioresources Research, College of Animal Science, Zhejiang University, Hangzhou, China.
    Ma, Qi
    Department of Big Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
    Yingjie, Wang
    Department of Orthopedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
    Weng, Xisheng
    Department of Orthopedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
    Ossipov, Dmitri A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Self-Healing Silk Fibroin-Based Hydrogel for Bone Regeneration: Dynamic Metal-Ligand Self-Assembly Approach2017Inngår i: Advanced Functional Materials, artikkel-id 1700591Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Despite advances in the development of silk fibroin (SF)-based hydrogels, current methods for SF gelation show significant limitations such as lack of reversible crosslinking, use of nonphysiological conditions, and difficulties in controlling gelation time. In the present study, a strategy based on dynamic metal-ligand coordination chemistry is developed to assemble SF-based hydrogel under physiological conditions between SF microfibers (mSF) and a polysaccharide binder. The presented SF-based hydrogel exhibits shear-thinning and autonomous self-healing properties, thereby enabling the filling of irregularly shaped tissue defects without gel fragmentation. A biomineralization approach is used to generate calcium phosphate-coated mSF, which is chelated by bisphosphonate ligands of the binder to form reversible crosslinkages. Robust dually crosslinked (DC) hydrogel is obtained through photopolymerization of acrylamide groups of the binder. DC SF-based hydrogel supports stem cell proliferation in vitro and accelerates bone regeneration in cranial critical size defects without any additional morphogenes delivered. The developed self-healing and photopolymerizable SF-based hydrogel possesses significant potential for bone regeneration application with the advantages of injectability and fit-to-shape molding.

  • 137.
    Shi, Liyang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Yannan, Zhao
    Center for Regenerative Medicine, State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P. R. China.
    Qifan, Xie
    Institute of Applied Bioresource, College of Animal Science, Zhejiang University, Hangzhou, Zhejiang, P. R. China.
    Caixia, Fan
    Center for Regenerative Medicine, State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P. R. China.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Jianwu, Dai
    Center for Regenerative Medicine, State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, P. R. China.
    Ossipov, Dmitri A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Moldable Hyaluronan Hydrogel Enabled by Dynamic Metal–Bisphosphonate Coordination Chemistry for Wound Healing2018Inngår i: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 7, nr 5, artikkel-id 1700973Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Biomaterial-based regenerative approaches would allow for cost-effective off-the-shelf solution for the treatment of wounds. Hyaluronan (HA)-based hydrogel is one attractive biomaterial candidate because it is involved in natural healing processes, including inflammation, granulation, and reepi-thelialization. Herein, dynamic metal–ligand coordination bonds are used to fabricate moldable supramolecular HA hydrogels with self-healing properties. To achieve reversible crosslinking of HA chains, the biopolymer is modified with pendant bisphosphonate (BP) ligands using carbodiimide coupling and chemoselective “click” reactions. Hydrogel is formed immediately after simple addition of silver (Ag+) ions to the solution of HA containing BP groups (HA-BP). Compared with previous HA-based wound healing hydrogels, the HA-BP·Ag+ hydrogel is highly suitable for clinical use as it can fill irregularly shaped wound defects without the need for premolding. The HA-BP·Ag+ hydrogel shows antimicrobial properties to both Gram-positive and Gram-negative bacterial strains, enabling prevention of infections in wound care. In vivo evaluation using a rat full-thickness skin wound model shows sig-nificantly lower wound remaining rate and a thicker layer of regenerated epidermis as compared with the group left without treatment. The presented moldable and self-healing supramolecular HA hydrogel with “ready-to-use” properties possesses a great potential for regenerative wound treatment.

  • 138.
    Shi, Liyang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Yu, Zhang
    College of Chemistry and Materials Science, Northwest University, Xi'an, Shaanxi, People's Republic of China.
    Ossipov, Dmitri A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Enzymatic degradation of hyaluronan hydrogels with different capacity for in situ bio-mineralization2018Inngår i: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 109, nr 2, artikkel-id e23090Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In situ cross-linked hyaluronan (HA) hydrogels with different capacities for biomineralization were prepared and their enzymatic degradation was monitored. Covalent incorporation of bisphosphonates (BPs) into HA hydrogel results in the increased stiffness of the hydrogel in comparison with the unmodified HA hydrogel of the same cross-linking density. The rate of enzymatic degradation of HABP hydrogel was significantly lower than the rate of degradation of control HA hydrogel in vitro. This effect is observed only in the presence of calcium ions that strongly bind to the matrix-anchored BP groups and promote further mineralization of the matrix. The degradation of the hydrogels was followed by noninvasive fluorescence measurements enabled after mild and chemoselective labeling of cross-linkable HA derivatives with a fluorescent tag.

  • 139. Sun, W.
    et al.
    Tiemessen, D. M.
    Sloff, M.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Gupta, B.
    Feitz, W. F. J.
    Daamen, W. F.
    van Kuppevelt, T. H.
    Geutjes, P. J.
    Oosterwijk, E.
    The influence of collagen density in cellular distribution2012Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, Vol. 6, nr suppl 1, s. 166-166Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Adequate cellular in-growth into biomaterials is one of the fundamental requirements in regenerative medicine. Type-I-collagen is the most commonly used material for soft tissue engineering, because it is nonimmunogenic and a highly porous network for cellular support. However, adequate cell in-growth and cell seeding has been suboptimal. Different densities of collagen scaffolds (0.3% to 0.8% (w/v)) with/without polymer knitting (poly-caprolactone (PCL)) were prepared. The structure of collagen scaffolds was characterized using scanning electronic microscopy (SEM) and HE staining. The mechanical strength of hybrid scaffolds was determined using tensile strength analysis. Cellular penetration and interconnectivity were evaluated using fluorescent bead distribution and human bladder smooth muscle cells and urothelium seeding. SEM and HE analysis showed the honeycomb structure and the hybrid scaffolds were adequately connected. The hybrid scaffolds were much stronger than collagen alone. The distribution of the beads and cells were highly dependent on the collagen density: at lower densities the beads and cells were more evenly distributed and penetrated deeper into the scaffold. The lower density collagen scaffolds showed remarkably deeper cellular penetration and by combining it with PCL knitting the tensile strength was enhanced. This study indicated that a 0.4% hybrid scaffold strengthened with knitting achieved the best cellular distribution.

  • 140. Sun, Weilun
    et al.
    Tiemessen, Dorien M.
    Sloff, Marije
    Lammers, Rianne J.
    de Mulder, Eric L. W.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Gupta, Bhuvanesh
    Feitz, Wout F. J.
    Daamen, Willeke F.
    van Kuppevelt, Toin H.
    Geutjes, Paul J.
    Oosterwijk, Egbert
    Improving the Cell Distribution in Collagen-Coated Poly-Caprolactone Knittings2012Inngår i: TISSUE ENG PART C-ME, ISSN 1937-3384, Vol. 18, nr 10, s. 731-739Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Adequate cellular in-growth into biomaterials is one of the fundamental requirements of scaffolds used in regenerative medicine. Type I collagen is the most commonly used material for soft tissue engineering, because it is nonimmunogenic and a highly porous network for cellular support can be produced. However, in general, adequate cell in-growth and cell seeding has been suboptimal. In this study we prepared collagen scaffolds of different collagen densities and investigated the cellular distribution. We also prepared a hybrid polymer-collagen scaffold to achieve an optimal cellular distribution as well as sufficient mechanical strength. Collagen scaffolds [ranging from 0.3% to 0.8% (w/v)] with and without a mechanically stable polymer knitting [polycaprolactone (PCL)] were prepared. The porous structure of collagen scaffolds was characterized using scanning electron microscopy and hematoxylin-eosin staining. The mechanical strength of hybrid scaffolds (collagen with or without PCL) was determined using tensile strength analysis. Cellular in-growth and interconnectivity were evaluated using fluorescent bead distribution and human bladder smooth muscle cells and human urothelium seeding. The lower density collagen scaffolds showed remarkably deeper cellular penetration and by combining it with PCL knitting the tensile strength was enhanced. This study indicated that a hybrid scaffold prepared from 0.4% collagen strengthened with knitting achieved the best cellular distribution.

  • 141.
    Sångeland, Christofer
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Mogensen, Ronnie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Brandell, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Mindemark, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Stable Cycling of Sodium Metal All-Solid-State Batteries with Polycarbonate-Based Polymer Electrolytes2019Inngår i: ACS APPLIED POLYMER MATERIALS, ISSN 2637-6105, Vol. 1, nr 4, s. 825-832Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Solid polymer electrolytes based on high-molecular-weight poly(trimethylene carbonate) (PTMC) in combination with NaFSI salt were investigated for application in sodium batteries. The polycarbonate host material proved to be able to dissolve large amounts of salt, at least up to a carbonate:Na+ ratio of 1:1. Combined DSC, conductivity, and FTIR data indicated the formation of a percolating network of salt clusters along with the transition to a percolation-type ion transport mechanism at the highest salt concentrations. While the highest total ionic conductivities were seen at the highest salt concentrations (up to a remarkable 5 x 10(-5) S cm(-1) at 25 degrees C at a 1:1 carbonate:Na+ ratio), the most stable battery performance was seen at a more moderate salt loading of 5:1 carbonate:Na+, reaching >80 cycles at a stable capacity of similar to 90 mAh g(-1) at 60 degrees C in a sodium metal/Prussian blue cell. The results highlight the importance of the choice of salt and salt concentration on electrolyte performance as well as demonstrate the potential of utilizing polycarbonate-based electrolytes in sodium-based energy storage systems.

  • 142.
    Tan, Semra
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Strukturkemi.
    Walus, Sylwia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Strukturkemi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Gustafsson, Torbjörn
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Strukturkemi.
    Brandell, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Strukturkemi.
    Poly(ether amine) and cross-linked poly(propylene oxide) diacrylate thin-film polymer electrolyte for 3D-microbatteries2010Inngår i: Electrochemistry communications, ISSN 1388-2481, E-ISSN 1873-1902, Vol. 12, nr 11, s. 1498-1500Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This paper presents a novel thin-film electrolyte of a 2:1 blend of polyetheramine (glyceryl poly(oxypropylene)) and cross-linked oligomeric poly(propylene oxide) diacrylate with LiTFSI. The polyetheramine acts as a surfactant, and can thereby be applied as a conformal coating on complex surfaces-here demonstrated for porous LiFePO4 cathodes-making it useful for 3D-microbatteries. The poly(propylene oxide) diacrylate blends with the surfactant and is easily UV cross-linked, thereby ensuring good mechanical stability. Electrolytes, ∼ 2 μm thick, were casted onto LiFePO 4 cathodes and cycled against metallic lithium, displaying stable discharge capacities of ∼ 8 mAh/g at room temperature and ∼ 120 mAh/g at 60 °C. The electrolyte showed conductivities of 3.45 × 10 - 6 and 5.80 × 10- 5 S cm- 1 at room temperature and 60 °C, respectively.

  • 143.
    Varghese, Oommen P.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Podiyan, Oommen
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Wang, S
    Kisiel, Marta
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Injectable hyaluronic acid hydrogel for bone tissue engineering2012Inngår i: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, Vol. 23, nr supplement 3, s. 2-Artikkel i tidsskrift (Fagfellevurdert)
  • 144.
    Wang, Shujiang
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Insights into dynamic covalent chemistry for bioconjugation applications2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Dynamic covalent chemistry (DCC) is currently exploited in several areas of biomedical applications such as in drug discovery, sensing, molecular separation, catalysis etc. Hydrazone and oxime chemistry have several advantages, such as mild reaction conditions, selectivity, efficiency, and biocompatibility and therefore, have the potential to be for bioconjugation applications. However, these reactions suffer from major drawbacks of slow reaction rate and poor bond stability under physiological conditions. In this regard, the work presented in this thesis focuses on designing novel bioconjugation reactions amenable under physiological conditions with tunable reaction kinetics and conjugation stability.

    The first part of the thesis presents different strategies of dynamic covalent reactions utilized for biomedical applications. In the next part, a detailed study related to the mechanism and catalysis of oxime chemistry was investigated in the presence of various catalysts. Aniline, carboxylate and saline were selective as target catalysts and their reaction kinetics were compared under physiological conditions (Paper I and II). Then we attempted to explore the potential of those chemistries in fabricating 3D hydrogel scaffolds for regenerative medicine application. A novel mild and regioselective method was devised to introduce an aldehyde moiety onto glycosaminoglycans structure. This involved the introduction of amino glycerol to glycosaminoglycans, followed by regioselective oxidation of tailed flexible diol without affecting the C2-C3 diol groups on the disaccharide repeating unit. The oxidation rate of the tailed flexible diol was 4-times faster than that of C2-C3 diol groups of native glycosaminoglycan. This strategy preserves the structural integrity of the glycosaminoglycans and provides a functional aldehyde moiety (Paper III). Further, different types of hydrazones were designed and their hydrolytic stability under acidic condition was carefully evaluated. The hydrazone linkage with the highest hydrolytic stability was utilized in the preparation of extracellular matrix hydrogel for delivery of bone morphogenetic proteins 2 in bone regeneration (Paper IV) and studied for controlled release of the growth factor (Paper III).

    In summary, this thesis presents a selection of strategies for designing bioconjugation chemistries that possess tunable stability and reaction kinetics under physiological conditions. These chemistries are powerful tools for conjugation of biomolecules for the biomedical applications.

    Delarbeid
    1. Insights into the Mechanism and Catalysis of Oxime Coupling Chemistry at Physiological pH
    Åpne denne publikasjonen i ny fane eller vindu >>Insights into the Mechanism and Catalysis of Oxime Coupling Chemistry at Physiological pH
    2015 (engelsk)Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 21, nr 15, s. 5980-5985Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The dynamic covalent-coupling reaction involving alpha-effect nucleophiles has revolutionized bioconjugation approaches, due to its ease and high efficiency. Key to its success is the discovery of aniline as a nucleophilic catalyst, which made this reaction feasible under physiological conditions. Aniline however, is not so effective for keto substrates. Here, we investigate the mechanism of aniline activation in the oxime reaction with aldehyde and keto substrates. We also present carboxylates as activating agents that can promote the oxime reaction with both aldehyde and keto substrates at physiological pH. This rate enhancement circumvents the influence of alpha-effect by forming H-bonds with the rate-limiting intermediate, which drives the reaction to completion. The combination of aniline and carboxylates had a synergistic effect, resulting in a similar to 14-31-fold increase in reaction rate at pD 7.4 with keto substrates. The biocompatibility and efficiency of carboxylate as an activating agent is demonstrated by performing cell-surface oxime labeling at physiological pH using acetate, which showed promising results that were comparable with aniline.

    Emneord
    ketones, kinetics, coupling reaction, oxime, reaction mechanisms
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-252690 (URN)10.1002/chem.201406458 (DOI)000352506500042 ()25737419 (PubMedID)
    Tilgjengelig fra: 2015-05-25 Laget: 2015-05-11 Sist oppdatert: 2017-12-04bibliografisk kontrollert
    2. Saline catalyse oxime reaction at physiological pH: overcoming a major limitation of bioorthogonal reaction
    Åpne denne publikasjonen i ny fane eller vindu >>Saline catalyse oxime reaction at physiological pH: overcoming a major limitation of bioorthogonal reaction
    Vise andre…
    (engelsk)Inngår i: Artikkel i tidsskrift (Fagfellevurdert) Submitted
    Abstract [en]

    We have discovered a simple and versatile reaction condition for oxime mediated bioconjugation reaction that could be adapted for both aldehyde and keto substrates. We found that saline accelerated the oxime kinetics in a concentration dependent manner under physiological conditions. The reaction mechanism is validated by computational studies, and the versatility of the reaction is demonstrated by cell-surface labeling experiments. Saline offers an efficient and non-toxic catalytic option for performing the bioorthogonal-coupling reaction of biomolecules at the physiological pH. This saline mediated bioconjugation reaction represents the most bio-friendly, mild and versatile approach for conjugating sensitive biomolecules and does not require any extensive purification step.

    Emneord
    Oxime reaction, catalysis, kinetics, labeling
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-328905 (URN)
    Tilgjengelig fra: 2017-09-04 Laget: 2017-09-04 Sist oppdatert: 2017-09-07bibliografisk kontrollert
    3. Mild and Efficient Strategy for Site-Selective Aldehyde Modification of Glycosaminoglycans: Tailoring Hydrogels with Tunable Release of Growth Factor
    Åpne denne publikasjonen i ny fane eller vindu >>Mild and Efficient Strategy for Site-Selective Aldehyde Modification of Glycosaminoglycans: Tailoring Hydrogels with Tunable Release of Growth Factor
    2013 (engelsk)Inngår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 14, nr 7, s. 2427-2432Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Aldehydes have been used as an important bioorthogonal chemical reporter for conjugation of large polymers and bioactive substances. However, generating aldehyde functionality on carbohydrate-based biopolymers without changing its native chemical structure has always persisted as a challenging task. The common methods employed to achieve this require harsh reaction conditions, which often compromise the structural integrity and biological function of these sensitive molecules. Here we report a mild and simple method to graft aldehydes groups on glycosaminoglycans (GAGs) in a site-selective manner without compromising the structural integrity of the biopolymer. This regio-selective modification was achieved by conjugating the amino-glycerol moiety on the carboxylate residue of the polymer, which allowed selective cleavage of pendent diol groups without interfering with the C2C3 diol groups of the native glucopyranose residue. Kinetic evaluation of this reaction demonstrated significant differences in second-order reaction rate for periodate oxidation (by four-orders of magnitude) between the two types of vicinal diols. We employed this chemistry to develop aldehyde modifications of sulfated and nonsulfated GAGs such as hyaluronic acid (HA), heparin (HP), and chondroitin sulfate (CS). We further utilized these aldehyde grafted GAGs to tailor extracellular matrix mimetic injectable hydrogels and evaluated its rheological properties. The composition of the hydrogels was also found to modulate release of therapeutic protein such as FGF-2, demonstrating controlled release (60%) for over 14 days. In short, our result clearly demonstrates a versatile strategy to graft aldehyde groups on sensitive biopolymers under mild conditions that could be applied for various bioconjugation and biomedical applications such as drug delivery and regenerative medicine.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-204978 (URN)10.1021/bm400612h (DOI)000321793700035 ()
    Merknad

    De två (2) första författarna delar förstaförfattarskapet.

    Tilgjengelig fra: 2013-08-16 Laget: 2013-08-13 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    4. Smart Design of Stable Extracellular Matrix Mimetic Hydrogel: Synthesis, Characterization, and In Vitro and In Vivo Evaluation for Tissue Engineering
    Åpne denne publikasjonen i ny fane eller vindu >>Smart Design of Stable Extracellular Matrix Mimetic Hydrogel: Synthesis, Characterization, and In Vitro and In Vivo Evaluation for Tissue Engineering
    Vise andre…
    2013 (engelsk)Inngår i: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 23, nr 10, s. 1273-1280Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The simplicity and versatility of hydrazone crosslinking has made it a strategy of choice for the conjugation of bioactive molecules. However, the labile nature of hydrazone linkages and reversibility of this coupling reaction restricts its full potential. Based on the fundamental understanding of hydrazone stability, this problem is circumvented by resonance-stabilization of a developing N2 positive charge in a hydrazone bond. A novel chemistry is presented to develop a resilient hydrazone bond that is stable and non- reversible under physiological conditions. A carbodihydrazide (CDH) type hydrazide derivative of the biomolecule forms intrinsically stabilized hydrazone-linkages that are nearly 15-fold more stable at pH 5 than conventional hydrazone. This chemoselective coupling reaction is catalyst-free, instantaneous, and virtually non-cleavable under physiological conditions, therefore can serve as a catalyst-free alternative to click chemistry. This novel crosslinking reaction is used to tailor a hyaluronan hydrogel, which delivered exceptional hydrolytic stability, mechanical properties, low swelling, and controlled enzymatic degradation. These desired characteristics are achieved without increasing the chemical crosslinking. The in vivo evaluation of this hydrogel revealed neo-bone with highly ordered collagen matrix mimicking natural bone regeneration. The proximity ligation assay or PLA is used to detect blood vessels, which highlighted the quality of engineered tissue.

    Emneord
    biomimetics, biomedical applications, hydrogels, tissue engineering, hyaluronic acid
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-198387 (URN)10.1002/adfm.201201698 (DOI)000316196100007 ()
    Tilgjengelig fra: 2013-04-15 Laget: 2013-04-15 Sist oppdatert: 2017-12-06bibliografisk kontrollert
  • 145.
    Wang, Shujiang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Gurav, Deepanjali
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Oommen, Oommen Podiyan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Varghese, Oommen P
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Insights into the Mechanism and Catalysis of Oxime Coupling Chemistry at Physiological pH2015Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 21, nr 15, s. 5980-5985Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The dynamic covalent-coupling reaction involving alpha-effect nucleophiles has revolutionized bioconjugation approaches, due to its ease and high efficiency. Key to its success is the discovery of aniline as a nucleophilic catalyst, which made this reaction feasible under physiological conditions. Aniline however, is not so effective for keto substrates. Here, we investigate the mechanism of aniline activation in the oxime reaction with aldehyde and keto substrates. We also present carboxylates as activating agents that can promote the oxime reaction with both aldehyde and keto substrates at physiological pH. This rate enhancement circumvents the influence of alpha-effect by forming H-bonds with the rate-limiting intermediate, which drives the reaction to completion. The combination of aniline and carboxylates had a synergistic effect, resulting in a similar to 14-31-fold increase in reaction rate at pD 7.4 with keto substrates. The biocompatibility and efficiency of carboxylate as an activating agent is demonstrated by performing cell-surface oxime labeling at physiological pH using acetate, which showed promising results that were comparable with aniline.

  • 146.
    Wang, Shujiang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Nawale, Ganesh N.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Kadekar, Sandeep
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Oommen, Oommen P.
    Tampere Univ Technol, Bioengn & Nanomed Lab, Fac Biomed Sci & Engn, Tampere 33720, Finland.;BioMediTech Inst, Tampere 33720, Finland..
    Jena, Naresh K.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Chakraborty, Sudip
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Varghese, Oommen P.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Saline Accelerates Oxime Reaction with Aldehyde and Keto Substrates at Physiological pH2018Inngår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikkel-id 2193Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have discovered a simple and versatile reaction condition for oxime mediated bioconjugation reaction that could be adapted for both aldehyde and keto substrates. We found that saline accelerated the oxime kinetics in a concentration-dependent manner under physiological conditions. The reaction mechanism is validated by computational studies, and the versatility of the reaction is demonstrated by cell-surface labeling experiments. Saline offers an efficient and non-toxic catalytic option for performing the bioorthogonal-coupling reaction of biomolecules at the physiological pH. This saline mediated bioconjugation reaction represents the most biofriendly, mild and versatile approach for conjugating sensitive biomolecules and does not require any extensive purification step.

  • 147.
    Wang, Shujiang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Nawale, Ganesh N.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Kadekar, Sandeep
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Oommen, Oommen P.
    Tampere University of Technology, and BioMediTech Institute, Finland.
    Jena, Naresh K.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Chakraborty, Sudip
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Varghese, Oommen P.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Saline catalyse oxime reaction at physiological pH: overcoming a major limitation of bioorthogonal reactionInngår i: Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have discovered a simple and versatile reaction condition for oxime mediated bioconjugation reaction that could be adapted for both aldehyde and keto substrates. We found that saline accelerated the oxime kinetics in a concentration dependent manner under physiological conditions. The reaction mechanism is validated by computational studies, and the versatility of the reaction is demonstrated by cell-surface labeling experiments. Saline offers an efficient and non-toxic catalytic option for performing the bioorthogonal-coupling reaction of biomolecules at the physiological pH. This saline mediated bioconjugation reaction represents the most bio-friendly, mild and versatile approach for conjugating sensitive biomolecules and does not require any extensive purification step.

  • 148.
    Wang, Shujiang
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Univ Montreal, Maisonneuve Rosemont Hosp Res Ctr, Montreal, PQ, Canada;Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada.
    Nawale, Ganesh N.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Oommen, Oommen P.
    Tampere Univ, Fac Med & Hlth Technol, Bioengn & Nanomed Lab, Korkeakoulunkatu 3, Tampere 33720, Finland;Tampere Univ, BioMediTech Inst, Korkeakoulunkatu 3, Tampere 33720, Finland.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Varghese, Oommen P.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Influence of ions to modulate hydrazone and oxime reaction kinetics to obtain dynamically cross-linked hyaluronic acid hydrogels2019Inngår i: Polymer Chemistry, ISSN 1759-9954, E-ISSN 1759-9962, Vol. 10, nr 31, s. 4322-4327Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Dynamic covalent chemistry forming hydrazone and oxime linkages is attractive due to its simplicity, selectivity and compatibility under aqueous conditions. However, the low reaction rate at physiological pH hampers its use in biomedical applications. Herein, we present different monovalent and bivalent aqueous salt solutions as bio-friendly, non-toxic catalysts which can drive the hydrazone and oxime reactions with excellent efficacy at physiological pH. Direct comparison of hydrazone and oxime reactions using a small molecule model, without any salt catalysis, indicated that oxime formation is 6-times faster than hydrazone formation. Addition of different salts (NaCl, NaBr, KCl, LiCl, LiClO4, Na2SO4, MgCl2 and CaCl2) accelerated the pseudo-first-order reaction kinetics by similar to 1.2-4.9-fold for acylhydrazone formation and by similar to 1.5-6.9-fold for oxime formation, in a concentration-dependent manner. We further explored the potential of such catalysts to develop acylhydrazone and oxime cross-linked hyaluronic acid (HA) hydrogels with different physicochemical properties without changing the degree of chemical modification. Analogous to the small molecule model system, the addition of monovalent and divalent salts as catalysts significantly reduced the gelling time. The gelling time for the acylhydrazone cross-linked HA-hydrogel (1.6 wt%) could be reduced from 300 min to 1.2 min by adding 100 mM CaCl2, while that for the oxime cross-linked HA-hydrogel (1.2 wt%) could be reduced from 68 min to 1.1 min by adding 50 mM CaCl2. This difference in the gelling time also resulted in hydrogels with differential swelling properties as measured after 24 h. Our results are the first to demonstrate the use of salts, for catalyzing hydrogel formation under physiologically relevant conditions.

  • 149.
    Wang, Zhaohui
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Oorganisk kemi.
    Tammela, Petter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Nyholm, Leif
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Oorganisk kemi.
    Cellulose-based Supercapacitors: Material and Performance Considerations2017Inngår i: Advanced Energy Materials, ISSN 1614-6832, Vol. 7, nr 18, artikkel-id 1700130Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    One of the biggest challenges we will face over the next few decades is finding a way to power the future while maintaining strong socioeconomic growth and a clean environment. A transition from the use of fossil fuels to renewable energy sources is expected. Cellulose, the most abundant natural biopolymer on earth, is a unique, sustainable, functional material with exciting properties: it is low-cost and has hierarchical fibrous structures, a high surface area, thermal stability, hydrophilicity, biocompatibility, and mechanical flexibility, which makes it ideal for use in sustainable, flexible energy storage devices. This review focuses on energy storage applications involving different forms of cellulose (i.e., cellulose microfibers, nanocellulose fibers, and cellulose nanocrystals) in supercapacitors, with particular emphasis on new trends and performance considerations relevant to these fields. Recent advances and approaches to obtaining high capacity devices are evaluated and the limitations of cellulose-based systems are discussed. For the first time, a combination of device-specific factors such as electrode structures, mass loadings, areal capacities, and volumetric properties are taken into account, so as to evaluate and compare the energy storage performance and to better assess the merits of cellulose-based materials with respect to real applications.

  • 150.
    Wang, Zhaohui
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Oorganisk kemi.
    Tammela, Petter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Zhang, Peng
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Strömme, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Nyholm, Leif
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Oorganisk kemi.
    High areal and volumetric capacity sustainable all-polymer paper-based supercapacitors2014Inngår i: Journal of Materials Chemistry A, ISSN 2050-7488, Vol. 2, nr 39, s. 16761-16769Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    All-polymer paper-based electrodes with a thickness up to hundreds of micrometers (e.g. 290 mu m), large active mass loadings (>20 mg cm(-2)) and relatively high densities (1.23 g cm(-3)) can be straightforwardly obtained from pristine low-cost polypyrrole-cellulose composites by decreasing the porosity of the material via space engineering. By straightforward compression of the composites, compact capacitive storage devices with improved space utilization are obtained without significantly compromising the electrochemical performance of the devices. This indicates that the compression unlike other methods previously used to vary the porosity of these composites does not affect the distribution of the mesopores which mainly determines the electrochemical performance of the material. When used to manufacture green supercapacitors comprising entirely of environmentally friendly materials, the freestanding and binder-free porous yet dense electrodes yield an areal capacitance of 5.66 F cm(-2), a device volumetric energy density of 3.7 W h L-1 (based on the volume of the entire device) and the largest volumetric electrode capacitance of 236 F cm(-3) so far reported for conducting polymer-based electrodes. The presented results for symmetric supercapacitors containing aqueous electrolytes represent significant progress in the development of inexpensive and environmentally friendly high-performance paper-based energy storage devices.

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