uu.seUppsala universitets publikasjoner
Endre søk
Begrens søket
1234 151 - 168 of 168
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 151.
    Wolff, Max
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik.
    Saini, Apurve
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik.
    Simonne, David
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik. Univ Rennes 1, Inst Phys Rennes, Rennes, France.
    Adlmann, Franz
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik.
    Nelson, Andrew
    ANSTO, Lucas Heights, NSW, Australia.
    Time Resolved Polarised Grazing Incidence Neutron Scattering from Composite Materials2019Inngår i: Polymers, ISSN 2073-4360, E-ISSN 2073-4360, Vol. 11, nr 3, artikkel-id 445Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neutron scattering experiments are a unique tool in material science due to their sensitivity to light elements and magnetic induction. However, for kinetic studies the low brilliance at existing sources poses challenges. In the case of periodic excitations these challenges can be overcome by binning the scattering signal according to the excitation state of the sample. To advance into this direction we have performed polarised and time resolved grazing incidence neutron scattering measurements on an aqueous solution of the polymer F127 mixed with magnetic nano-particles. Magnetic nano-composites like this provide magnetically tuneable properties of the polymer crystal as well as magnetic meta-crystals. Even though the grazing incidence small angle scattering and polarised signals are too weak to be evaluated at this stage we demonstrate that such experiments are feasible. Moreover, we show that the intensity of the 111 Bragg peak of the fcc micellar crystal depends on the actual shear rate, with the signal being maximised when the shear rate is lowest (and vice-versa).

  • 152.
    Yan, Hongji
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Casalini, Tommaso
    Hulsart Billström, Gry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Wang, Shujiang
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Oommen, Oommen P.
    Salvalaglio, Matteo
    Larsson, Sune
    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.
    Varghese, Oommen P.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Synthetic design of growth factor sequestering extracellular matrix mimetic hydrogel for promoting in vivo bone formation2018Inngår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 161, s. 190-202Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 153.
    Yang, Xia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Multi-functional Hyaluronan Based Biomaterials for Biomedical Applications2014Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis presents strategies for constructing multi-functional biomaterials based on hyaluronan (HA) derivatives for various biomedical applications, such as drug delivery, tissue regeneration, and imaging biomaterials. The aim of this study is to improve the functionalities of HA biomaterials as well as simplify the preparation procedures.  Native HA polymer contains D-glucuronic acid residue with a carboxyl group per disaccharide unit that can be easily modified by carbodiimide-mediated amidation reaction. Therefore, we have designed a series of orthogonal groups (hydrazide, carbazate, aldehyde, and thiol) that can be linked to HA under mild conditions using the carbodiimide chemistry. Multiple functionalities can be introduced to the obtained HA derivatives via chemoselective “click”-type transformations.  

    The modified HA derivatives were used for the preparation of either nanogel particles (NPs) or bulk hydrogels. Due to “click” character of the reactions used, structural HA transformations were performed with high fidelity on different scales including molecular (polymers), nanometer (NPs), and a visible scale (bulk hydrogels). By linking pyrene or camptothecin to hydrophilic HA backbone, amphiphilic polymers were obtained and utilized as drug delivery carriers or prodrugs, respectively. Subsequently, physically loaded drug (doxorubicin) could be released upon degradation of HA carriers, while the chemically linked camptothecin was released intact by a thiol-triggered cleavage reaction. Bisphosphonated HA (HA-BP) polymers were prepared to induce hydrogel scaffold bio-mineralization for bone regeneration application. Moreover, we could recruit strong binding capacity of bisphosphonate (BP) groups to calcium ions for the formation of physically crosslinked HA-BP gel upon simple mixing of the polymer and calcium phosphate nanoparticle components. This gel was more stable in vivo compared to hydrazone crosslinked HA gels. Furthermore, the hydrogel composed of fluorine-19 (19F) linked HA polymer was successfully observed by both 1H and 19F MR imaging.        

    In conclusion, the presented herein study describes new approaches for building up multi-functional biomaterials from the HA-based blocks. The utilization of carbodiimide and click chemistries along with the enzymatic degradation of HA allowed simple and efficient interconversion between HA macromolecules, nanoparticles and macroscopic hydrogels. These HA-based biomaterials show high potential for use in the fields of drug delivery, bone regeneration, and imaging techniques.

    Delarbeid
    1. Modular approach to functional hyaluronic acid hydrogels using orthogonal chemical reactions
    Åpne denne publikasjonen i ny fane eller vindu >>Modular approach to functional hyaluronic acid hydrogels using orthogonal chemical reactions
    Vise andre…
    2010 (engelsk)Inngår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 46, nr 44, s. 8368-8370Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

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

    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot polymerkemi
    Identifikatorer
    urn:nbn:se:uu:diva-135363 (URN)10.1039/c0cc03055d (DOI)000283690400014 ()
    Tilgjengelig fra: 2010-12-07 Laget: 2010-12-06 Sist oppdatert: 2017-12-11bibliografisk kontrollert
    2. Preparation of hyaluronic acid nanoparticles via hydrophobic association assisted chemical cross-linking: an orthogonal modular approach
    Åpne denne publikasjonen i ny fane eller vindu >>Preparation of hyaluronic acid nanoparticles via hydrophobic association assisted chemical cross-linking: an orthogonal modular approach
    2011 (engelsk)Inngår i: Soft Matter, ISSN 1744-683X, E-ISSN 1744-6848, Vol. 7, nr 16, s. 7517-7525Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The objective of this study was to develop an efficient and stable drug delivery nanocarrier based on a dually functionalized hyaluronic acid (HA) derivative which could be used as a long circulating drug delivery vehicle. Self-assembled HA nanoparticles (HA NPs) were prepared by attaching pyrene to the HA backbone and the obtained physical NPs were stabilized by chemical cross-linking of the HA chains to form hydrophobic core-hydrophilic shell NPs. Orthogonal chemoselective reactions were applied for conversion of HA into its amphiphilic derivative and subsequent cross-linking of the formed micellar-type associates. Chemical stabilization of the physical HA associates afforded therefore very stable nanoparticles that could easily be re-suspended in aqueous media after freeze-drying. In contrast, freeze-drying of the uncross-linked physically associated particles resulted in a non-soluble material. Doxorubicin (DOX), a typical anticancer drug, was entrapped into HA NPs via ionic and/or hydrophobic interactions and used for in vitro drug release. Higher loading efficiency and the slower release profile of DOX from HA NPs were obtained with the hydrophobically encapsulated drug. We have shown that free HA NPs were readily taken up by NIH 3T3 cells without causing any toxicity to the cells, while the DOX-loaded HA NPs resulted in increased cell death comparable to the free drug. This study clearly showed the applicability of orthogonal chemoselective modifications for the synthesis of stable HA nanogel particles as a potential cancer-targeted drug delivery system.

    HSV kategori
    Forskningsprogram
    Kemi med inriktning mot polymerkemi
    Identifikatorer
    urn:nbn:se:uu:diva-158426 (URN)10.1039/c1sm05785e (DOI)000293412900049 ()
    Tilgjengelig fra: 2011-09-08 Laget: 2011-09-07 Sist oppdatert: 2017-12-08bibliografisk kontrollert
    3. A hyaluronic acid-camptothecin nanoprodrug with cytosolic mode of activation for targeting cancer
    Åpne denne publikasjonen i ny fane eller vindu >>A hyaluronic acid-camptothecin nanoprodrug with cytosolic mode of activation for targeting cancer
    Vise andre…
    2013 (engelsk)Inngår i: POLYM CHEM-UK, ISSN 1759-9954, Vol. 4, nr 17, s. 4621-4630Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    We have developed a nanoprodrug that enables the uptake by cancer cells and the subsequent intracellular activation. The nanoprodrug is composed of a cancer cell-targeting biopolymer, hyaluronic acid (HA), and an anti-cancer drug, camptothecin (CPT). The chemical linkage between the polymer and the drug is stable outside the cells, thus maintaining the drug in an "off" state. The specific uptake of the nanoprodrug by cancer cells should then lead to an environmental change that results in the cleavage of the linkage, liberating the drug and thus entering the "on" state. The natural cancer-targeting biopolymer HA was modified with aldehyde "click" groups. This "clickable" HA was then conjugated to CPT modified with a hydrazide linker using a mild hydrazone-coupling reaction. The linker consists of a thiol-activated self-immolative dithioethoxycarbonyl spacer, which is stable in PBS buffer but should be rapidly cleaved in the reductive cytosolic environment of cancer cells. The resulting HA-CPT nanoprodrug released CPT only at low levels in PBS buffer. However, the drug was efficiently cleaved after the addition of dithiothreitol (DTT). Consistent with these data, the HA-CPT nanoprodrug showed a 3-fold greater cytotoxicity to cancer cells compared to free CPT. Fluorescence microscopy confirmed the rapid and efficient uptake of the HA-CPT nanoprodrug by the cancer cells.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-207489 (URN)10.1039/c3py00402c (DOI)000323361300013 ()
    Tilgjengelig fra: 2013-09-17 Laget: 2013-09-16 Sist oppdatert: 2014-06-30bibliografisk kontrollert
    4. Direct ”Click” Synthesis of Hybrid Bisphosphonate-Hyaluronic Acid Hydrogel in Aqueous Solution for Biomineralization
    Åpne denne publikasjonen i ny fane eller vindu >>Direct ”Click” Synthesis of Hybrid Bisphosphonate-Hyaluronic Acid Hydrogel in Aqueous Solution for Biomineralization
    Vise andre…
    2012 (engelsk)Inngår i: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 24, nr 9, s. 1690-1697Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    We report the synthesis of injectable in situ forming hybrid hydrogel material and investigate its ability to support the mineralization process under mild conditions. To achieve this, we have prepared a hyaluronic acid (HA) derivative that is dually functionalized with cross-linkable hydrazide groups and bisphosphonate ligands (HA-hy-BP). The hybrid hydrogel can be formed by simple mixing of two solutions: the solution of HA-hy-BP and the Ca2+ ions containing solution of aldehyde-derivatized HA (HA-al). We found that the conjugation of BP, a P-C-P analogue of pyrophosphate, to the hydrogel matrix promotes an efficient and fast mineralization of the matrix. The mineralization is facilitated by the strong interaction between BP residues and Ca2+ ions that serve as nanometer-sized nucleation points for further calcium phosphate deposition within the HA hydrogel. Compared with previously reported hydrogel template-driven mineralization techniques, the present approach is maximally adapted for clinical settings since the formation of the hybrid takes place during quick mixing of the sterilized solutions. Moreover, the hybrid hydrogel is formed from in vivo degradable components of the extracellular matrix and therefore can be remodeled in vivo through concerted HA degradation and calcium phosphate mineralization.

    Emneord
    hybrid organic-inorganic materials, injectable materials, hydrogels, hyaluronic acid, mineralization
    HSV kategori
    Forskningsprogram
    Teknisk fysik med inriktning mot materialvetenskap; Kemi med inriktning mot polymerkemi
    Identifikatorer
    urn:nbn:se:uu:diva-171989 (URN)10.1021/cm300298n (DOI)000303628100019 ()
    Tilgjengelig fra: 2012-03-30 Laget: 2012-03-30 Sist oppdatert: 2019-04-24bibliografisk kontrollert
    5. Self-healing Hybrid Nanocomposites consisting of Bisphosphonated Hyaluronan and Calcium Phosphate Nanoparticles
    Åpne denne publikasjonen i ny fane eller vindu >>Self-healing Hybrid Nanocomposites consisting of Bisphosphonated Hyaluronan and Calcium Phosphate Nanoparticles
    Vise andre…
    2014 (engelsk)Inngår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, nr 25, s. 6918-6929Artikkel i tidsskrift (Fagfellevurdert) Published
    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.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-224369 (URN)10.1016/j.biomaterials.2014.05.003 (DOI)000338386800024 ()
    Tilgjengelig fra: 2014-05-09 Laget: 2014-05-09 Sist oppdatert: 2017-12-05bibliografisk kontrollert
    6. Injectable hyaluronic acid hydrogel for F-19 magnetic resonance imaging
    Åpne denne publikasjonen i ny fane eller vindu >>Injectable hyaluronic acid hydrogel for F-19 magnetic resonance imaging
    Vise andre…
    2014 (engelsk)Inngår i: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 110, s. 95-99Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    We report on a19F labeled injectable hyaluronic acid (HA) hydrogel that can be monitored by both 1H and 19F MR imaging. The HA based hydrogel formed via carbazone reaction can be obtained within a minute by simple mixing of HA-carbazate and HA-aldehyde derivatized polymers. 19F contrast agent was linked to with carbazate and thiol dually functionalized HA via orthogonal Michael addition reaction which afforded cross-linkable and 19F labeled HA. The 19F labeling of HA polymer did not affect the mechanical properties of the formed hydrogel. As a result, the shape of a hydrogel sample could be imaged very well by both 1H MRI and high resolution19F MRI. This hydrogel has high potential in clinical applications since it is injectable, biocompatible, and can be tracked in a minimally invasive manner. The present approach can be applied in preparation of injectable 19F labeled hydrogel biomaterials from other natural biomacromolecules.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-224259 (URN)10.1016/j.carbpol.2014.03.070 (DOI)000338005000013 ()
    Merknad

    Injectable hyaluronic acid hydrogel for 19F magnetic resonance imaging

    Tilgjengelig fra: 2014-05-09 Laget: 2014-05-07 Sist oppdatert: 2017-12-05bibliografisk kontrollert
  • 154.
    Yang, Xia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Akhtar, Sultan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Leifer, Klaus
    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.
    Development of multifunctional hyaluronic acid-based carriers by 'click' chemistry2012Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, Vol. 6, nr suppl 1, s. 191-192Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: We have developed methods to simultaneously introduce chemoselective groups to hyaluronic acid (HA) that can be crosslinked and used for immobilization of various molecules. It is easy to switch the functionalities of obtained materials through orthogonal ‘click’ chemistries.

    Methods: HA polymers were dually functionalized with hydrazide and thiol groups, or aldehyde groups. Different functional molecules such as bisphosphonate (BP) groups for mineralization or camptothecin (CPT) as anti-cancer drug can be linked to thiol groups. HA polymers were characterized by 1H, 31P NMR, and UV-Vis Spectroscopy. Characterizations of materials were performed using SEM, TEM, rheology, and colorimetric calcium assay.

    Results and discussion: The functional polymers were successfully synthesized. They can form hydrogels within 1 min with HA-aldehyde polymer. BP groups showed high affinity to calcium ions and inorganic nanoparticle phases were observed within BP containing hybrid hydrogel. On the other hand, CPT-linked HA polymer via S-S bond can self-assembled into nanoparticles, and the release of the drug is triggered by the addition of reduce agents (e.g. dithiothreitol).

    Conclusions: The use of orthogonal click modification opened a versatile way to prepare different kinds of HA based carriers with various functionalities by simple methods. The multifunctional HA polymers show high potentials to be used for drug delivery (pro-drug) or tissue regeneration (BP linked HA).

  • 155.
    Yang, Xia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Akhtar, Sultan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Rubino, Stefano
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Leifer, Klaus
    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.
    Direct ”Click” Synthesis of Hybrid Bisphosphonate-Hyaluronic Acid Hydrogel in Aqueous Solution for Biomineralization2012Inngår i: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 24, nr 9, s. 1690-1697Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We report the synthesis of injectable in situ forming hybrid hydrogel material and investigate its ability to support the mineralization process under mild conditions. To achieve this, we have prepared a hyaluronic acid (HA) derivative that is dually functionalized with cross-linkable hydrazide groups and bisphosphonate ligands (HA-hy-BP). The hybrid hydrogel can be formed by simple mixing of two solutions: the solution of HA-hy-BP and the Ca2+ ions containing solution of aldehyde-derivatized HA (HA-al). We found that the conjugation of BP, a P-C-P analogue of pyrophosphate, to the hydrogel matrix promotes an efficient and fast mineralization of the matrix. The mineralization is facilitated by the strong interaction between BP residues and Ca2+ ions that serve as nanometer-sized nucleation points for further calcium phosphate deposition within the HA hydrogel. Compared with previously reported hydrogel template-driven mineralization techniques, the present approach is maximally adapted for clinical settings since the formation of the hybrid takes place during quick mixing of the sterilized solutions. Moreover, the hybrid hydrogel is formed from in vivo degradable components of the extracellular matrix and therefore can be remodeled in vivo through concerted HA degradation and calcium phosphate mineralization.

  • 156.
    Yang, Xia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Kim, Jin-Chul
    beta-Cyclodextrin grafted polyethyleneimine hydrogel immobilizing hydrophobically modified glucose oxidase2011Inngår i: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 48, nr 4, s. 661-666Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Hydrogels which release their contents in response to glucose concentration were prepared by immobilizing glucose oxidase (GOD) into beta-cyclodextrin grafted polyethyleneimine hydrogels (PEI-beta CD hydrogel). For the tight immobilization, hydrophobically modified GOD (HmGOD) was prepared by reacting GOD with palmitic acid-N-hydroxysuccinimide ester (PA-NHS) in the molar ratio of 1:40. According to trinitrobenzene sulfonic acid (TNBS) assay, five palmitic acids were covalently attached to one GOD molecule. The activity of HmGOD was about 76% of native enzyme. The swelling ratios of HmGOD loaded hydrogels increased from about 960% to 1190% in 24 h, when glucose concentration was varied from 0 to 100 mg/dl. The % release in 48 h of fluorescein isothiocyanate dextran increased from about 53% to 89%, when glucose concentration was varied in the same range. Gluconic acid, produced by the enzymatic reaction, would protonate and swell the PEI-beta CD hydrogel, leading to a higher release.

  • 157.
    Yang, Xia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Kim, Jin-Chul
    Seo, Hee Jin
    Hydrogel of beta-cyclodextrin-Grafted Polyethyleneimine: pH-Sensitive Release2012Inngår i: Journal of Dispersion Science and Technology, ISSN 0193-2691, E-ISSN 1532-2351, Vol. 33, nr 8, s. 1233-1239Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Novel pH-sensitive hydrogels were prepared by grafting beta-cyclodextrin (beta CD) to polyethyleneimine (PEI) and cross-linking beta CD using epichlorohydrin (EPI). While the molar ratio of beta CD to PEI was kept to 1:50, the molar ratio of EPI to beta CD was varied so that it was 3/1, 5/1, and 10/1. When the EPI to beta CD ratio was higher, the degree of equilirium swelling and the percentage release were lower, possibly due to a higher cross-linking density. The % release of blue dextran was much less than that of fluorescein isothiocyanate-dextran (FITC-dextran). The electrostatic interaction of blue dextran with the hydrogel is believed to suppress the release of the dye. Among the hydrogels prepared in this work, the hydrogel prepared using the beta CD to EPI ratio of 1/5 was the most pH sensitive in terms of the degree of swelling and the degree of FITC-dextran release.

  • 158.
    Yang, Xia
    et al.
    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.
    Ossipov, Dmitri A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Preparation of hyaluronic acid nanoparticles via hydrophobic association assisted chemical cross-linking: an orthogonal modular approach2011Inngår i: Soft Matter, ISSN 1744-683X, E-ISSN 1744-6848, Vol. 7, nr 16, s. 7517-7525Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The objective of this study was to develop an efficient and stable drug delivery nanocarrier based on a dually functionalized hyaluronic acid (HA) derivative which could be used as a long circulating drug delivery vehicle. Self-assembled HA nanoparticles (HA NPs) were prepared by attaching pyrene to the HA backbone and the obtained physical NPs were stabilized by chemical cross-linking of the HA chains to form hydrophobic core-hydrophilic shell NPs. Orthogonal chemoselective reactions were applied for conversion of HA into its amphiphilic derivative and subsequent cross-linking of the formed micellar-type associates. Chemical stabilization of the physical HA associates afforded therefore very stable nanoparticles that could easily be re-suspended in aqueous media after freeze-drying. In contrast, freeze-drying of the uncross-linked physically associated particles resulted in a non-soluble material. Doxorubicin (DOX), a typical anticancer drug, was entrapped into HA NPs via ionic and/or hydrophobic interactions and used for in vitro drug release. Higher loading efficiency and the slower release profile of DOX from HA NPs were obtained with the hydrophobically encapsulated drug. We have shown that free HA NPs were readily taken up by NIH 3T3 cells without causing any toxicity to the cells, while the DOX-loaded HA NPs resulted in increased cell death comparable to the free drug. This study clearly showed the applicability of orthogonal chemoselective modifications for the synthesis of stable HA nanogel particles as a potential cancer-targeted drug delivery system.

  • 159.
    Yang, Xia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Lee, Hyeon Yong
    Kim, Jin-Chul
    Effect of Hydrophobic Comonomer Content on Assembling of Poly (N-isopropylacrylamide) and Thermal Properties2011Inngår i: Journal of Applied Polymer Science, ISSN 0021-8995, E-ISSN 1097-4628, Vol. 120, nr 4, s. 2346-2353Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Copolymers of N-isopropylacrylamide and octadecyl acrylate (PNO), of which the content of octadecyl acrylate (ODA) was 1.3% (PNO 1.5), 1.7% (PNO 2.0), and 3.0% (PNO 4.0), were prepared using a free radical reaction. Various assemblies were obtained depending on the concentration of PNOs and the contents of ODA. Hydrophobic interaction between ODA residues is likely to act as crosslinker. PNO 1.5 formed hydrogel at the concentration of 7%. With PNO 2.0, hydrogels were formed when the concentration was 5 and 7%. With PNO 4.0, the opaque gel was obtained when the concentration was 7%. Upon heating across the lower critical solution temperature, the hydrogels shrank but the opaque gel was broken down into a suspension. At 40 degrees C, the release degrees of fluorescein isothiocyanate-dextran were much smaller than those of release at 23 degrees C. The temperature-sensitive release is due to temperature-sensitive swelling ratio.

  • 160.
    Yang, Xia
    et al.
    China Acad Engn Phys, Inst Nucl Phys & Chem, 64 Mianshan Rd, Mianyang 621900, Sichuan, Peoples R China.
    Shi, Liyang
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Guo, Xin
    China Acad Engn Phys, Inst Nucl Phys & Chem, 64 Mianshan Rd, Mianyang 621900, Sichuan, Peoples R China.
    Gao, Jinxu
    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.
    Convergent in situ assembly of injectable lipogel for enzymatically controlled and targeted delivery of hydrophilic molecules2016Inngår i: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 154, s. 62-69Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Applications of liposomes are limited due to their rapid blood clearance and non-specific biodistribution. Surface modification of liposomes could overcome these disadvantages. However, direct coating of liposome surface may cause disruption of liposomes. Herein we present a “top-down” method to coat liposomes in situ with tumor (CD44 receptor) targeting polymer, hyaluronan (HA), by taking advantages of “click” type chemistries and enzymatic degradation. Liposomes entrapped within HA gel were stable without leaking of small cargo molecules from the interior of the liposomes. This injectable liposome-in-hydrogel (lipogel) drug delivery system can achieve sequential two-step release: (1) liposomes release from lipogel after HA degradation; (2) small molecules release from liposomes after the liposomes disruption (either before or after cellular uptake). Similarly to HA coating, this strategy could be used for in situ “top-down” modification of liposomes with other targeting biopolymers. Additionally, it provides the possibility to deliver different types of molecules from two compartments of the lipogel, i.e. large biomacromolecules from the exterior of liposomes and small hydrophilic molecules from the interior of liposomes, locally and systemically.

  • 161.
    Yang, Xia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Yi, Sun
    Radboud University Nijmegen Medical Centre.
    Kootala, Sujit
    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.
    Heerschap, Arend
    Radboud University Nijmegen Medical Centre.
    Ossipov, Dmitri
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Injectable hyaluronic acid hydrogel for F-19 magnetic resonance imaging2014Inngår i: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 110, s. 95-99Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We report on a19F labeled injectable hyaluronic acid (HA) hydrogel that can be monitored by both 1H and 19F MR imaging. The HA based hydrogel formed via carbazone reaction can be obtained within a minute by simple mixing of HA-carbazate and HA-aldehyde derivatized polymers. 19F contrast agent was linked to with carbazate and thiol dually functionalized HA via orthogonal Michael addition reaction which afforded cross-linkable and 19F labeled HA. The 19F labeling of HA polymer did not affect the mechanical properties of the formed hydrogel. As a result, the shape of a hydrogel sample could be imaged very well by both 1H MRI and high resolution19F MRI. This hydrogel has high potential in clinical applications since it is injectable, biocompatible, and can be tracked in a minimally invasive manner. The present approach can be applied in preparation of injectable 19F labeled hydrogel biomaterials from other natural biomacromolecules.

  • 162.
    Zhang, Yu
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström.
    Hyaluronan Based Biomaterials with Imaging Capacity for Tissue Engineering2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis presents the preparation of hyaluronan-based biomaterials with imaging capability and their application as scaffolds in tissue engineering. First, we have synthesized HA derivatives functionalized with different chemoselective groups. Then, functional ligands with capacities for hydrophobic drug loading, imaging, and metal ion coordination were chemically conjugated to HA by chemoselective reactions with these groups. An injectable in situ forming HA hydrogel was prepared by hydrazone cross-linking between hybrid iron-oxide nanogel and HA-aldehyde (paper-I). The degradation of this hydrogel could be monitored by MRI and UV-vis spectroscopy since it contained iron oxide as a contrast agent and pyrene as a fluorescent probe. Additionally, this hydrogel has a potential for a delivery of hydrophobic drugs due to its pyrene hydrophobic domains. The degradation study showed that degradability of the hydrogel was correlated with its structure. Based on the obtained results, disulfide cross-linked and fluorescently labeled hydrogels with different HA concentration were established as a model to study the relationship between the structure of the hydrogel and its degradability (paper-II). We demonstrated that disulfide cross-linked HA hydrogel could be tracked non-invasively by fluorescence imaging. It was proved that the in vivo degradation behavior of the hydrogel is predictable basing on its in vitro degradation study. In paper-III, we developed a disulfide cross-linked HA hydrogel for three-dimensional (3D) cell culture. In order to improve cell viability and adhesion to the matrix, HA derivatives were cross-linked in the presence of fibrinogen undergoing polymerization upon the action of thrombin. It led to the formation of an interpenetrating double network (IPN) of HA and fibrin. The results of 3D cell culture experiments revealed that the IPN hydrogel provides the cells with a more stable environment for proliferation. The results of the cellular studies were also supported by in vitro degradation of IPN monitored by fluorescence measurements of the degraded products. In paper-IV, the effect of biomineralization on hydrogel degradation was evaluated in a non-invasive manner in vitro. For this purpose, two types of fluorescently labeled hydrogels with the different ability for biomineralization were prepared. Fluorescence spectroscopy was applied to monitor degradation of the hydrogels in vitro under two different conditions in longitudinal studies. Under the supply of Ca2+ ions, the BP-modified hydrogel showed the tendency to bio-mineralization and reduction of the rate of degradation. Altogether, the performed studies showed the importance of imaging of hydrogel biomaterials in the design of optimized scaffolds for tissue engineering.

    Delarbeid
    1. Injectable In Situ Forming Hybrid Iron Oxide-Hyaluronic Acid Hydrogel for Magnetic Resonance Imaging and Drug Delivery
    Åpne denne publikasjonen i ny fane eller vindu >>Injectable In Situ Forming Hybrid Iron Oxide-Hyaluronic Acid Hydrogel for Magnetic Resonance Imaging and Drug Delivery
    Vise andre…
    2014 (engelsk)Inngår i: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 14, nr 9, s. 1249-1259Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The development of multimodal in situ cross-linkable hyaluronic acid nanogels hybridized with iron oxide nanoparticles is reported. Utilizing a chemoselective hydrazone coupling reaction, the nanogels are converted to a macroscopic hybrid hydrogel without any additional reagent. Hydrophobic cargos remain encapsulated in the hydrophobic domains of the hybrid hydrogel without leakage. However, hydrogel degradation with hyaluronidase liberates iron oxide nanoparticles. This allows the utilization of imaging agents as tracers of the hydrogel degradation. UV-vis spectrometry and MRI studies reveal that the degradability of the hydrogels correlates with their structure. The hydrogels presented here are very promising theranostic tools for hyaluronidase-mediated delivery of hydrophobic drugs, as well as imaging of hydrogel degradation and tracking of degradation products in vivo.

    Emneord
    hybrid organic-inorganic nanogels, hyaluronan hydrogels, in situ cross-linking, iron oxide nanoparticles, magnetic resonance imaging
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-236090 (URN)10.1002/mabi.201400117 (DOI)000342921900005 ()
    Tilgjengelig fra: 2014-11-17 Laget: 2014-11-12 Sist oppdatert: 2017-12-05bibliografisk kontrollert
    2. Non-invasive in vitro and in vivo monitoring of degradation of fluorescently labeled hyaluronan hydrogels for tissue engineering applications
    Åpne denne publikasjonen i ny fane eller vindu >>Non-invasive in vitro and in vivo monitoring of degradation of fluorescently labeled hyaluronan hydrogels for tissue engineering applications
    Vise andre…
    2016 (engelsk)Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 30, s. 188-198Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Tracking of degradation of hydrogels-based biomaterials in vivo is very important for rational design of tissue engineering scaffolds that act as delivery carriers for bioactive factors. During the process of tissue development, an ideal scaffold should remodel at a rate matching with scaffold degradation. To reduce amount of animals sacrificed, non-invasive in vivo imaging of biomaterials is required which relies on using of biocompatible and in situ gel forming compounds carrying suitable imaging agents. In this study we developed a method of in situ fabrication of fluorescently labeled and injectable hyaluronan (HA) hydrogel based on one pot sequential use of Michael addition and thiol-disulfide exchange reactions for the macromolecules labeling and cross-linking respectively. Hydrogels with different content of HA were prepared and their enzymatic degradation was followed in vitro and in vivo using fluorescence multispectral imaging. First, we confirmed that the absorbance of the matrix-linked near-IR fluorescent IRDye (R) 800CW agent released due to the matrix enzymatic degradation in vitro matched the amount of the degraded hydrogel measured by classical gravimetric method. Secondly, the rate of degradation was inversely proportional to the hydrogel concentration and this structure-degradation relationship was similar for both in vitro and in vivo studies. It implies that the degradation of this disulfide cross-linked hyaluronan hydrogel in vivo can be predicted basing on the results of its in vitro degradation studies. The compliance of in vitro and in vivo methods is also promising for the future development of predictive in vitro tissue engineering models. Statement of significance The need for engineered hydrogel scaffolds that deliver bioactive factors to endogenous progenitor cells in vivo via gradual matrix resorption and thus facilitate tissue regeneration is increasing with the aging population. Importantly, scaffold should degrade at a modest rate that will not be too fast to support tissue growth nor too slow to provide space for tissue development. The present work is devoted to longitudinal tracking of a hydrogel material in vivo from the time of its implantation to the time of complete resorption without sacrificing animals. The method demonstrates correlation of resorption rates in vivo and in vitro for hydrogels with varied structural parameters. It opens the possibility to develop predictive in vitro models for tissue engineered scaffolds and reduce animal studies.

    Emneord
    Hyaluronan, Hydrogel degradation, Non-invasive imaging, Spinal cord, Tissue engineering
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-277793 (URN)10.1016/j.actbio.2015.11.053 (DOI)000368563600017 ()26621694 (PubMedID)
    Forskningsfinansiär
    EU, FP7, Seventh Framework Programme
    Merknad

    De två första författarna delar förstaförfattarskapet.

    Tilgjengelig fra: 2016-02-23 Laget: 2016-02-23 Sist oppdatert: 2017-11-30bibliografisk kontrollert
    3. Hyaluronic acid-fibrin interpenetrating double network hydrogel prepared in situ by orthogonal disulfide cross-linking reaction for biomedical applications
    Åpne denne publikasjonen i ny fane eller vindu >>Hyaluronic acid-fibrin interpenetrating double network hydrogel prepared in situ by orthogonal disulfide cross-linking reaction for biomedical applications
    Vise andre…
    2016 (engelsk)Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 38, s. 23-32Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    To strengthen the mechanical properties of a fibrin gel and improve its applicability as a scaffold for tissue engineering (TE) applications, a strategy for the in situ preparation of the interpenetrating network (IPN) of fibrin and hyaluronic acid (HA) was developed on the basis of simultaneous and orthogonal fibrinogenesis and disulfide cross-linking. The synthetic pathway included the preparation of mutually reactive HA derivatives bearing thiol and 2-dithiopyridyl groups. Combining thiol-derivatized HA with thrombin and 2-dithiopyridyl-modified HA with fibrinogen and then mixing the obtained liquid formulations afforded IPNs with fibrin-resembling fibrillar architectures at different ratios between fibrin and HA networks. The formation of two networks was confirmed by conducting reference experiments with the compositions lacking one of the four components. The composition of 2% (w/v) fibrin and 1% (w/v) HA showed the highest storage modulus (G'), as compared with the single network counterparts. The degradation of fibrin in IPN hydrogels was slower than that in pure fibrin gels both during incubation of the hydrogels in a fibrin-cleaving nattokinase solution and during the culturing of cells after their encapsulation in the hydrogels. Together with the persistence of HA network, it permitted longer cell culturing time in the IPN. Moreover, the proliferation and spreading of MG63 cells that express the hyaluronan receptor CD44 in IPN hydrogel was increased, as compared with its single network analogues. These results are promising for tunable ECM-based materials for TE and regenerative medicine. Statement of Significance The present work is devoted to in situ fabrication of injectable extracellular matrix hydrogels through simultaneous generation of networks of fibrin and hyaluronic acid (HA) that interpenetrate each other. This is accomplished by combination of enzymatic fibrin cross-linking with orthogonal disulphide cross-linking of HA. High hydrophilicity of HA prevents compaction of the fibrin network, while fibrin provides an adhesive environment for in situ encapsulated cells. The interpenetrating network hydrogel shows an increased stiffness along with a lower degradation rate of fibrin in comparison to the single fibrin network. As a result, the cells have sufficient time for the remodelling of the scaffold. This new approach can be applied for modular construction of in vitro tissue models and tissue engineering scaffolds in vivo.

    Emneord
    Interpenetrating hydrogel, Fibrin, Hyaluronic acid, Biodegradation, 3D cell culture
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-300044 (URN)10.1016/j.actbio.2016.04.041 (DOI)000378963800003 ()27134013 (PubMedID)
    Forskningsfinansiär
    EU, European Research Council
    Tilgjengelig fra: 2016-08-02 Laget: 2016-08-02 Sist oppdatert: 2017-11-28bibliografisk kontrollert
    4. Enzymatic degradation of hyaluronan hydrogels with different capacity for in situ bio-mineralization
    Åpne denne publikasjonen i ny fane eller vindu >>Enzymatic degradation of hyaluronan hydrogels with different capacity for in situ bio-mineralization
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-300791 (URN)
    Tilgjengelig fra: 2016-08-14 Laget: 2016-08-13 Sist oppdatert: 2016-09-02
  • 163.
    Zhang, Yu
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Heher, Philipp
    Ludwig Boltzmann Inst Expt & Clin Traumatol, Austrian Cluster Tissue Regenerat, Donaueschingenstr 13, A-1200 Vienna, Austria.;Trauma Care Consult GmbH, Gonzagagasse 11-25, A-1010 Vienna, Austria..
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Redl, Heinz
    Ludwig Boltzmann Inst Expt & Clin Traumatol, Austrian Cluster Tissue Regenerat, Donaueschingenstr 13, A-1200 Vienna, Austria.;Trauma Care Consult GmbH, Gonzagagasse 11-25, A-1010 Vienna, Austria..
    Ossipov, Dmitri A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Hyaluronic acid-fibrin interpenetrating double network hydrogel prepared in situ by orthogonal disulfide cross-linking reaction for biomedical applications2016Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 38, s. 23-32Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To strengthen the mechanical properties of a fibrin gel and improve its applicability as a scaffold for tissue engineering (TE) applications, a strategy for the in situ preparation of the interpenetrating network (IPN) of fibrin and hyaluronic acid (HA) was developed on the basis of simultaneous and orthogonal fibrinogenesis and disulfide cross-linking. The synthetic pathway included the preparation of mutually reactive HA derivatives bearing thiol and 2-dithiopyridyl groups. Combining thiol-derivatized HA with thrombin and 2-dithiopyridyl-modified HA with fibrinogen and then mixing the obtained liquid formulations afforded IPNs with fibrin-resembling fibrillar architectures at different ratios between fibrin and HA networks. The formation of two networks was confirmed by conducting reference experiments with the compositions lacking one of the four components. The composition of 2% (w/v) fibrin and 1% (w/v) HA showed the highest storage modulus (G'), as compared with the single network counterparts. The degradation of fibrin in IPN hydrogels was slower than that in pure fibrin gels both during incubation of the hydrogels in a fibrin-cleaving nattokinase solution and during the culturing of cells after their encapsulation in the hydrogels. Together with the persistence of HA network, it permitted longer cell culturing time in the IPN. Moreover, the proliferation and spreading of MG63 cells that express the hyaluronan receptor CD44 in IPN hydrogel was increased, as compared with its single network analogues. These results are promising for tunable ECM-based materials for TE and regenerative medicine. Statement of Significance The present work is devoted to in situ fabrication of injectable extracellular matrix hydrogels through simultaneous generation of networks of fibrin and hyaluronic acid (HA) that interpenetrate each other. This is accomplished by combination of enzymatic fibrin cross-linking with orthogonal disulphide cross-linking of HA. High hydrophilicity of HA prevents compaction of the fibrin network, while fibrin provides an adhesive environment for in situ encapsulated cells. The interpenetrating network hydrogel shows an increased stiffness along with a lower degradation rate of fibrin in comparison to the single fibrin network. As a result, the cells have sufficient time for the remodelling of the scaffold. This new approach can be applied for modular construction of in vitro tissue models and tissue engineering scaffolds in vivo.

  • 164.
    ZHANG, YU
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström.
    Shi, Liyang
    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.
    Enzymatic degradation of hyaluronan hydrogels with different capacity for in situ bio-mineralizationManuskript (preprint) (Annet vitenskapelig)
  • 165.
    Zhang, Yu
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Sun, Yi
    Yang, Xia
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Heerschap, Arend
    Ossipov, Dmitri A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Injectable In Situ Forming Hybrid Iron Oxide-Hyaluronic Acid Hydrogel for Magnetic Resonance Imaging and Drug Delivery2014Inngår i: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 14, nr 9, s. 1249-1259Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The development of multimodal in situ cross-linkable hyaluronic acid nanogels hybridized with iron oxide nanoparticles is reported. Utilizing a chemoselective hydrazone coupling reaction, the nanogels are converted to a macroscopic hybrid hydrogel without any additional reagent. Hydrophobic cargos remain encapsulated in the hydrophobic domains of the hybrid hydrogel without leakage. However, hydrogel degradation with hyaluronidase liberates iron oxide nanoparticles. This allows the utilization of imaging agents as tracers of the hydrogel degradation. UV-vis spectrometry and MRI studies reveal that the degradability of the hydrogels correlates with their structure. The hydrogels presented here are very promising theranostic tools for hyaluronidase-mediated delivery of hydrophobic drugs, as well as imaging of hydrogel degradation and tracking of degradation products in vivo.

  • 166.
    Zhang, Yuning
    et al.
    KTH Royal Inst Technol, Dept Fibre & Polymer Technol, SE-10044 Stockholm, Sweden.
    Andren, Oliver C. J.
    KTH Royal Inst Technol, Dept Fibre & Polymer Technol, SE-10044 Stockholm, Sweden.
    Nordström, Randi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Fan, Yanmiao
    KTH Royal Inst Technol, Dept Fibre & Polymer Technol, SE-10044 Stockholm, Sweden.
    Malmsten, Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Mongkhontreerat, Surinthra
    Sweden Polymer Factory Sweden AB, SE-11428 Stockholm, Sweden.
    Malkoch, Michael
    KTH Royal Inst Technol, Dept Fibre & Polymer Technol, SE-10044 Stockholm, Sweden.
    Off-Stoichiometric Thiol-Ene Chemistry to Dendritic Nanogel Therapeutics2019Inngår i: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, Vol. 29, nr 18, artikkel-id 1806693Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A novel platform of dendritic nanogels is herein presented, capitalizing on the self-assembly of allyl-functional polyesters based on dendritic-linear-dendritic amphiphiles followed by simple cross-linking with complementary monomeric thiols via UV initiated off-stoichiometric thiol-ene chemistry. The facile approach enabled multigram creation of allyl reactive nanogel precursors, in the size range of 190-295 nm, being readily available for further modifications to display a number of core functionalities while maintaining the size distribution and characteristics of the master batch. The nanogels are evaluated as carriers of a spread of chemotherapeutics by customizing the core to accommodate each individual cargo. The resulting nanogels are biocompatible, displaying diffusion controlled release of cargo, maintained therapeutic efficacy, and decreased cargo toxic side effects. Finally, the nanogels are found to successfully deliver pharmaceuticals into a 3D pancreatic spheroids tumor model.

  • 167.
    Åkerlund, Elin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Development of polymer based composite filaments for 3D printing2019Independent thesis Advanced level (professional degree), 20 poäng / 30 hpOppgave
    Abstract [en]

    The relatively new and still growing field of 3D-printing has opened up the possibilities to manufacture patient-specific medical devices with high geometrical accuracy in a precise and quick manner. Additionally, biocompatible materials are a demand for all medical applications while biodegradability is of importance when developing scaffolds for tissue growth for instance. With respect to this, this project consisted of developing biocompatible and bioresorbable polymer blend and composite filaments, for fused deposition modeling (FDM) printing. Poly(lactic acid) (PLA) and polycaprolactone (PCL) were used as supporting polymer matrix while hydroxyapatite (HA), a calcium phosphate with similar chemical composition to the mineral phase of human bone, was added to the composites to enhance the biological activity. PLA and PCL content was varied between 90–70 wt% and 10-30 wt%, respectively, while the HA content was 15 wt% in all composites. All materials were characterized in terms of mechanical properties, thermal stability, chemical composition and morphology. An accelerated degradation study of the materials was also executed in order to investigate the degradation behavior as well as the impact of the degradation on the above mentioned properties. The results showed that all processed materials exhibited higher mechanical properties compared to the human trabecular bone, even after degradation with a mass loss of around 30% for the polymer blends and 60% for the composites. It was also apparent that the mineral accelerated the polymer degradation significantly, which can be advantageous for injuries with faster healing time, requiring only support for a shorter time period.

  • 168.
    Östman, Anders
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström.
    RAFT-Polymerization of N-Vinyl Pyrrolidone and MethylMethacrylate for Synthesis of Functional Co-BlockpolymerBinders for Solid Electrolyte Batteries.2015Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
1234 151 - 168 of 168
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf