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  • 1.
    Ajalloueian, F.
    et al.
    Isfahan Univ Technol, Dept Text Engn, Ctr Excellence Appl Nanotechnol, Esfahan, Iran..
    Fransson, M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Tavanai, H.
    Isfahan Univ Technol, Dept Text Engn, Ctr Excellence Appl Nanotechnol, Esfahan, Iran..
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Magnusson, Peetra
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala Univ, Dept Immunol Genet & Pathol IGP, Uppsala, Sweden..
    Arpanaei, A.
    Natl Inst Genet Engn & Biotechnol, Dept Ind & Environm Biotechnol, Tehran, Iran..
    Comparing PLGA and PLGA/Chitosan Nanofibers Seeded by Msc: A Cell-scaffold Interaction Study2015Ingår i: Tissue Engineering. Part A, ISSN 1937-3341, E-ISSN 1937-335X, Vol. 21, s. S406-S407Artikel i tidskrift (Övrigt vetenskapligt)
  • 2.
    Ajalloueian, F.
    et al.
    Tech Univ Denmark, Copenhagen, Denmark..
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Fossum, M.
    Karolinska Inst, Stockholm, Sweden..
    Chronakis, I. S.
    Tech Univ Denmark, Copenhagen, Denmark..
    Integrated Micro/Nanofibrous PLGA-Collagen Scaffold: an Optimized Method for Plastic Compression of Collagen into PLGA Microfibers2015Ingår i: Tissue Engineering. Part A, ISSN 1937-3341, E-ISSN 1937-335X, Vol. 21, s. S347-S347Artikel i tidskrift (Övrigt vetenskapligt)
  • 3.
    Ajalloueian, Fatemeh
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Fransson, Moa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Tavanai, Hossein
    Massuni, Mohammad
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    LeBlanc, Katarina
    Arpanaei, Ayyoob
    Magnusson, Peetra
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Investigation of Human Mesenchymal Stromal Cells Cultured on PLGA orPLGA/Chitosan Electrospun Nanofibers2015Ingår i: Journal of Bioprocessing & Biotechniques, ISSN 2155-9821, Vol. 5, nr 6, artikel-id 230Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We compared the viability, proliferation, and differentiation of human Mesenchymal Stromal Cells (MSC)after culture on poly(lactic-co-glycolic acid) (PLGA) and PLGA/chitosan (PLGA/CH) hybrid scaffolds. We appliedconventional and emulsion electrospinning techniques, respectively, for the fabrication of the PLGA and PLGA/CH scaffolds. Electrospinning under optimum conditions resulted in an average fiber diameter of 166 ± 33 nmfor the PLGA/CH and 680 ± 175 nm for the PLGA scaffold. The difference between the tensile strength of thePLGA and PLGA/CH nanofibers was not significant, but PLGA/CH showed a significantly lower tensile modulusand elongation at break. However, it should be noted that the extensibility of the PLGA/CH was higher than thatof the nanofibrous scaffolds of pure chitosan. As expected, a higher degree of hydrophilicity was seen with PLGA/CH, as compared to PLGA alone. The biocompatibility of the PLGA and PLGA/CH scaffolds was compared usingMTS assay as well as analysis by scanning electron microscopy and confocal microscopy. The results showed thatboth scaffold types supported the viability and proliferation of human MSC, with significantly higher rates on PLGA/CH nanofibers. Nonetheless, an analysis of gene expression of MSC grown on either PLGA or PLGA/CH showed asimilar differentiation pattern towards bone, nerve and adipose tissues.

  • 4.
    Ajalloueian, Fatemeh
    et al.
    Tech Univ Denmark, DTU Food, Nanobio Sci Res Grp, Lyngby, Denmark.
    Lemon, Greg
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Chronakis, Ioannis S.
    Tech Univ Denmark, DTU Food, Nanobio Sci Res Grp, Lyngby, Denmark.
    Fossum, Magdalena
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden; Karolinska Inst, Ctr Mol Med, CMM 02, Stockholm, Sweden; Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Dept Paediat Surg, Sect Urol, Stockholm, Sweden.
    Bladder biomechanics and the use of scaffolds for regenerative medicine in the urinary bladder2018Ingår i: Nature reviews. Urology, ISSN 1759-4812, E-ISSN 1759-4820, Vol. 15, nr 3, s. 155-174Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    The urinary bladder is a complex organ with the primary functions of storing urine under low and stable pressure and micturition. Many clinical conditions can cause poor bladder compliance, reduced capacity, and incontinence, requiring bladder augmentation or use of regenerative techniques and scaffolds. To replicate an organ that is under frequent mechanical loading and unloading, special attention towards fulfilling its biomechanical requirements is necessary. Several biological and synthetic scaffolds are available, with various characteristics that qualify them for use in bladder regeneration in vitro and in vivo, including in the treatment of clinical conditions. The biomechanical properties of the native bladder can be investigated using a range of mechanical tests for standardized assessments, as well as mathematical and computational bladder biomechanics. Despite a large body of research into tissue engineering of the bladder wall, some features of the native bladder and the scaffolds used to mimic it need further elucidation. Collection of comparable reference data from different animal models would be a helpful tool for researchers and will enable comparison of different scaffolds in order to optimize characteristics before entering preclinical and clinical trials.

  • 5.
    Ajalloueian, Fatemeh
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Tavanai, Hossein
    Hilborn, Jons
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Donzel-Gargand, Olivier
    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.
    Wickham, Abeni
    Arpanaei, Ayyoob
    Emulsion Electrospinning as an Approach to Fabricate PLGA/Chitosan Nanofibers for Biomedical Applications2014Ingår i: BioMed Research International, ISSN 2314-6133, Vol. 2014, s. 475280-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Novel nanofibers from blends of polylactic-co-glycolic acid (PLGA) and chitosan have been produced through an emulsion electrospinning process. The spinning solution employed polyvinyl alcohol (PVA) as the emulsifier. PVA was extracted from the electrospun nanofibers, resulting in a final scaffold consisting of a blend of PLGA and chitosan. The fraction of chitosan in the final electrospun mat was adjusted from 0 to 33%. Analyses by scanning and transmission electron microscopy show uniform nanofibers with homogenous distribution of PLGA and chitosan in their cross section. Infrared spectroscopy verifies that electrospun mats contain both PLGA and chitosan. Moreover, contact angle measurements show that the electrospun PLGA/chitosanmats are more hydrophilic than electrospun mats of pure PLGA. Tensile strengths of 4.94 MPa and 4.21 MPa for PLGA/chitosan in dry and wet conditions, respectively, illustrate that the polyblend mats of PLGA/chitosan are strong enough for many biomedical applications. Cell culture studies suggest that PLGA/chitosan nanofibers promote fibroblast attachment and proliferation compared to PLGA membranes. It can be assumed that the nanofibrous composite scaffold of PLGA/chitosan could be potentially used for skin tissue reconstruction.

  • 6.
    Ajalloueian, Fatemeh
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Zeiai, S.
    Fossum, M.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    A bedside collagen-PLGA nanofibrous construct for autologous transplantation of minced bladder mucosal2012Ingår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, Vol. 6, nr suppl 1, s. 128-128Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: Bladder regeneration using minced bladder mucosa is an alternative to costly and time-consuming conventional in vitro culturing of urothelial cells. In this method, the uroepithelium expands in vivo and the patient body appears as an incubator. With our preliminary successes, designing an appropriate scaffold that supports in vivo cell expansion and surgical handling in a clinical setting was our aim. This study, investigates cell expansion in a hybrid construct of collagen/poly (lactic-co-glycolide)(PLGA).

    Materials and methods: An electrospun PLGA mat was placed on a semi-gel collagen inside a mold and covered with a second collagen layer. After gel formation, minced particles of pig bladder mucosa were seeded on the hybrid construct and then processed by plastic compression (PC). The scaffolds were incubated for 2, 4 and 6 weeks in vitro for further studies.

    Results: Tensile tests show an increase in tensile strength of 0.6 ± 0.1 MPa in PC collagen to 3.6 ± 1.1 MPa in hybrid construct. Morphological studies, histological staining and SEM show that the construct has kept its integrity during the time and proliferated urothelial cells have reached confluence after 4 weeks and a multi-layered urothelium after 6 weeks.

    Conclusion: We have designed a mechanically robust scaffold that permits surgical handling and tissue expansion in vivo. The construct is easy-to-use for clinical application in an ordinary surgical operating theater for bladder regeneration.

  • 7.
    Ajalloueian, Fatemeh
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Zeiai, Said
    Fossum, Magdalena
    Hilborn, Jöns G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Constructs of electrospun PLGA, compressed collagen and minced urothelium for minimally manipulated autologous bladder tissue expansion2014Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, nr 22, s. 5741-5748Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bladder regeneration based on minced bladder mucosa in vivo expansion is an alternative to in vitro culturing of urothelial cells. Here, we present the design of a hybrid, electrospun poly(lactic-co-glycolide) (PLGA) - plastically compressed (PC) collagen scaffold that could allow in vivo bladder mucosa expansion. Optimisation of electrospinning was performed in order to obtain increased pore sizes and porosity to consolidate the construct and to support neovascularisation and tissue ingrowth. Tensile tests showed an increase in average tensile strength from 0.6 MPa for PC collagen to 3.57 MPa for the hybrid construct. The optimised PLGA support scaffold was placed between two collagen gels, and the minced tissue was distributed either on top or both on top and inside the construct prior to PC; this was then cultured for up to four weeks. Morphology, histology and SEM demonstrated that the construct maintained its integrity throughout cell culture. Cells from minced tissue migrated, expanded and re-organised to a confluent cell layer on the top of the construct after two weeks and formed a multilayered urothelium after four weeks. Cell morphology and phenotype was typical for urothelial mucosa during tissue culture. (C) 2014 Elsevier Ltd. All rights reserved.

  • 8.
    Ajalloueian, Fatemeh
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Zeiai, Said
    Rojas, Ramiro
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Fossum, Magdalena
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    One-Stage Tissue Engineering of Bladder Wall Patches for an Easy-To-Use Approach at the Surgical Table2013Ingår i: Tissue Engineering. Part C, Methods, ISSN 1937-3384, E-ISSN 1937-3392, Vol. 19, nr 9, s. 688-696Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We present a method for producing a cell-scaffold hybrid construct at the bedside. The construct is composed of plastic-compressed collagen together with a poly(e-caprolactone) (PCL)-knitted mesh that yields an integrated, natural-synthetic scaffold. This construct was evaluated by seeding of minced bladder mucosa, followed by proliferation in vitro. High mechanical strength in combination with a biological environment suitable for tissue growth was achieved through the creation of a hybrid construct that showed an increased tensile strength (17.9 +/- 2.6 MPa) when compared to plastic-compressed collagen (0.6 +/- 0.12 MPa). Intimate contact between the collagen and the PCL fabric was required to ensure integrity without delamination of the construct. This contact was achieved by surface alkaline hydrolysis of the PCL, followed by adsorption of poly(vinyl) alcohol. The improvement in hydrophilicity of the PCL-knitted mesh was confirmed through water contact angle measurements, and penetration of the collagen into the mesh was evaluated by scanning electron microscopy (SEM). Particles of minced bladder mucosa tissue were seeded onto this scaffold, and the proliferation was followed for 6 weeks in vitro. Results obtained from phase contrast microscopy, SEM, and histological staining indicated that cells migrated from the minced tissue particles and reorganized on the scaffold. Cells were viable and proliferative, with morphological features characteristic of urothelial cells. Proliferation reached the point at which a multilayer with a resemblance to stratified urothelium was achieved. This successful method could potentially be used for in vivo applications in reconstructive urology as an engineered autologous tissue transplant without the requirement for in vitro culture before transplantation.

  • 9.
    Aulin, C.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Jensen-Waern, M.
    Ekman, S.
    Hagglund, M.
    Engstrand, T.
    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.
    Hedenqvist, P.
    Cartilage repair of experimentally 11 induced osteochondral defects in New Zealand White rabbits2013Ingår i: Laboratory Animals. Journal of the Laboratory Animal Science Association, ISSN 0023-6772, E-ISSN 1758-1117, Vol. 47, nr 1, s. 58-65Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Articular cartilage has a limited capacity for self-repair in adult humans, and methods used to stimulate regeneration often result in re-growth of fibrous cartilage, which has lower durability. No current treatment option can provide complete repair. The possibility of growth factor delivery into the joint for cartilage regeneration after injury would be an attractive treatment option. A full thickness osteochondral defect of 4 mm in diameter and 2 mm deep was created by mechanical drilling in the medial femoral condyle in 20 female adult New Zealand White rabbits. In an attempt to improve regeneration a hyaluronic hydrogel system, with or without bone morphogenetic protein-2 (BMP-2) was delivered intraarticularly. The contralateral joint defect was treated with saline as control. Throughout the study, rabbits were clinically examined and after 12 (n = 6) or 24 (n = 9) weeks, the rabbits were euthanized and the joints evaluated by histology. The defects healed with fibrocartilage like tissue, and the filling of the defects ranged from less than 25% to complete. The healing of the defects varied both inter- and intra-group wise. Treatment with hyaluronan gel with or without BMP-2 had no effect on cartilage regeneration compared with controls. Instead, severe ectopic bone formation was found in seven joints treated with BMP-2. In conclusion, the present study shows that neither treatment with hyaluronic gel alone, nor in combination with BMP-2, improves the healing of an induced cartilage defect in rabbits. It further shows that BMP-2 can induce ectopic bone formation, which severely affects the functionality of the joint.

  • 10. Backly, R. E.
    et al.
    Todeschi, M. R.
    Varghese, Oommen
    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.
    Cancedda, R.
    Mastrogiacomo, M.
    Host cell recruitment patterns by BMP-2 releasing hyaluronic acid gels in a mouse subcutaneous model2014Ingår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, s. 65-65Artikel i tidskrift (Övrigt vetenskapligt)
  • 11. Barman, Jharna
    et al.
    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.
    2 '-N-Guanidino, 4 '-C-ethylene bridged thymidine (GENA-T) modified oligonucleotide exhibits triplex formation with excellent enzymatic stability2015Ingår i: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 5, nr 16, s. 12257-12260Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Here we present the synthesis and characterization of a new 2'-N-Guanidino, 4'-C-ethylene bridged thymidine (GENA-T) modified oligonucleotide possessing North-locked sugar conformation. Incorporation of GENA-T nucleotide though did not change the thermal stability of the oligonucleotides toward the complementary RNA; it significantly increased the stability of the parallel triplex at pH 7. The melting temperature of the triplex was increased by +9.5 degrees C as compared to that of the isosequential unmodified sequence. Moreover this modification imparted exceptional nuclease stability to the oligonucleotides for over 33 h. This study clearly demonstrates that GENA-T modified oligonucleotides could improve triplex formation with phenomenal enzymatic stability and could be used for various biomedical applications.

  • 12.
    Becker, Juliane
    et al.
    DEUTSCHES KREBSFORSCHUNGSZENTRUM, RUPRECHT-KARLS-UNIVERSITAT HEIDELBERG.
    Jäschke, Andres
    DEUTSCHES KREBSFORSCHUNGSZENTRUM, RUPRECHT-KARLS-UNIVERSITAT HEIDELBERG.
    Samanta, Ayan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. DEUTSCHES KREBSFORSCHUNGSZENTRUM, RUPRECHT-KARLS-UNIVERSITAT HEIDELBERG.
    Wiessler, Manfred
    DEUTSCHES KREBSFORSCHUNGSZENTRUM, RUPRECHT-KARLS-UNIVERSITAT HEIDELBERG.
    MULTIPLE ORTHOGONAL LABELLING OF OLGONUCLEOTIDES2016Patent (Övrig (populärvetenskap, debatt, mm))
    Abstract [en]

    In Summary, the present invention concerns a method for multiple orthogonal labelling of oligonucleotides, preferably RNA or DNA, by simultaneously performing the inverse Diels-Alder reaction (DAinv) and the copper-catalyzed click reaction (CuAAC), wherein the method is employed in a single step by just adding the different reaction components together and incubating the aqueous reaction mixture prefer ably for one hour at room temperature. In detail, the reaction components are one or more N-modified labels, a copper compound, a stabilizing ligand, a reducing agent and one or more electron-deficient label-modified dienes that are added together with an at least double-modified oligonucleotide having one more nucleotides containing one or more N3-re active groups and one or more electron-rich dienophiles, wherein a terminal alkyne moiety is preferably used as N3-re active group(s) and afrans-cyclooctene moiety or norbornene is preferably used as electron-rich dienophile(s), more pref erably frans-cyclooctene. Therefore, the present invention provides a one-pot method for post-synthetic multiple orthogonal labeling of oligonucleotides, which allows the site-specific introduction of more than one label, preferably of at least two labels into oligonucleotides after solid-phase synthesis, wherein the DAinv takes place on the dienophile modification only and the CuAAC selectively takes place on the N3-reactive group modification.

  • 13.
    Bergfelt, Andreas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Block Copolymer Electrolytes: Polymers for Solid-State Lithium Batteries2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The use of solid polymer electrolytes (SPEs) for lithium battery devices is a rapidly growing research area. The liquid electrolytes that are used today are inflammable and harmful towards the battery components. The adoption of SPEs could drastically improve this situation, but they still suffer from a too low performance at ambient temperatures for most practical applications. However, by increasing the operating temperature to between 60 °C and 90 °C, the electrolyte performance can be drastically increased. The drawback of this approach, partly, is that parasitic side reactions become noticeable at these elevated temperatures, thus affecting battery lifetime and performance. Furthermore, the ionically conductive polymer loses its mechanical integrity, thus triggering a need for an external separator in the battery device.

    One way of combining both mechanical properties and electrochemical performance is to design block copolymer (BCP) electrolytes, that is, polymers that are tailored to combine one ionic conductive block with a mechanical block, into one polymer. The hypothesis is that the BCP electrolytes should self-assemble into well-defined microphase separated regions in order to maximize the block properties. By varying monomer composition and structure of the BCP, it is possible to design electrolytes with different battery device performance. In Paper I and Paper II two types of methacrylate-based triblock copolymers with different mechanical blocks were synthesized, in order to evaluate morphology, electrochemical performance, and battery performance. In Paper III and Paper IV a different strategy was adopted, with a focus on diblock copolymers. In this strategy, the ethylene oxide was replaced by poly(e-caprolactone) and poly(trimethylene carbonate) as the lithium-ion dissolving group. The investigated mechanical blocks in these studies were poly(benzyl methacrylate) and polystyrene. The battery performance for these electrolytes was superior to the methacrylate-based battery devices, thus resulting in stable battery cycling at 40 °C and 30 °C.

    Delarbeten
    1. d8-poly(methyl methacrylate)-poly[(oligo ethylene glycol) methyl ether methacrylate] tri-block-copolymer electrolytes: Morphology, conductivity and battery performance
    Öppna denna publikation i ny flik eller fönster >>d8-poly(methyl methacrylate)-poly[(oligo ethylene glycol) methyl ether methacrylate] tri-block-copolymer electrolytes: Morphology, conductivity and battery performance
    Visa övriga...
    2017 (Engelska)Ingår i: Polymer, ISSN 0032-3861, E-ISSN 1873-2291, Vol. 131, s. 234-242Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    A series of deuterated tri-block copolymers with the general structure d(8)-PMMA-POEGMA-d(8)-PMMA, with variation in d(8)-PMMA chain length, were synthesized using sequential controlled radical polymerization (ATRP). Solid polymer electrolytes (SPEs) were produced by blending tri-block copolymers and lithium bis(trifluoro methylsulfonate) (LiTFSI). Small-angle neutron scattering (SANS) was used to study the bulk morphology of the deuterated tri-block copolymer electrolyte series at 25 degrees C, 60 degrees C and 95 degrees C. The lack of a second T-g in DSC analysis together with modelling with the random phase approximation model (RPA) confirmed that the electrolytes are in the mixed state, with negative Flory-Huggins interaction parameters. AC impedance spectroscopy was used to study the ionic conductivity of the SPE series in the temperature interval 30 degrees C-90 degrees C, and a battery device was constructed to evaluate a 25 wt% d(8)-PMMA electrolyte. The Li | SPE | LiFePO4 cell cycled at 60 degrees C, giving a discharge capacity of 120 mAh g(-1), while cyclic voltammetry showed that the SPE was stable at 60 degrees C.

    Nationell ämneskategori
    Polymerkemi
    Identifikatorer
    urn:nbn:se:uu:diva-337667 (URN)10.1016/j.polymer.2017.10.044 (DOI)000415014300026 ()
    Forskningsfinansiär
    Vetenskapsrådet
    Tillgänglig från: 2018-01-03 Skapad: 2018-01-03 Senast uppdaterad: 2018-02-22Bibliografiskt granskad
    2. Poly(benzyl methacrylate)-Poly[(oligo ethylene glycol) methyl ether methacrylate] Triblock-Copolymers as Solid Electrolyte for Lithium Batteries
    Öppna denna publikation i ny flik eller fönster >>Poly(benzyl methacrylate)-Poly[(oligo ethylene glycol) methyl ether methacrylate] Triblock-Copolymers as Solid Electrolyte for Lithium Batteries
    2018 (Engelska)Ingår i: Solid State Ionics, ISSN 0167-2738, E-ISSN 1872-7689, Vol. 321, s. 55-61Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    A triblock copolymer of benzyl methacrylate and oligo(ethylene glycol) methyl ether methacrylate was polymerized to form the general structure PBnMA-POEGMA-PBnMA, using atom transfer radical polymerization (ATRP). The block copolymer (BCP) was blended with lithium bis(trifluoro methylsulfonate) (LiTFSI) to form solid polymer electrolytes (SPEs). AC impedance spectroscopy was used to study the ionic conductivity of the SPE series in the temperature interval 30 °C to 90 °C. Small-angle X-ray scattering (SAXS) was used to study the morphology of the electrolytes in the temperature interval 30 °C to 150 °C. By using benzyl methacrylate as a mechanical block it was possible to tune the microphase separation by the addition of LiTFSI, as proven by SAXS. By doing so the ionic conductivity increased to values higher than ones measured on a methyl methacrylate triblock copolymer-based electrolyte in the mixed state, which was investigated in an earlier paper by our group. A Li|SPE|LiFePO4 half-cell was constructed and cycled at 60 °C. The cell produced a discharge capacity of about 100 mAh g−1 of LiFePO4 at C/10, and the half-cell cycled for more than 140 cycles.

    Nationell ämneskategori
    Polymerkemi
    Forskningsämne
    Kemi med inriktning mot polymerkemi
    Identifikatorer
    urn:nbn:se:uu:diva-340851 (URN)10.1016/j.ssi.2018.04.006 (DOI)000437372200009 ()
    Forskningsfinansiär
    EnergimyndighetenStandUp
    Tillgänglig från: 2018-02-04 Skapad: 2018-02-04 Senast uppdaterad: 2018-10-11Bibliografiskt granskad
    3. ε-Caprolactone-based solid polymer electrolytes for lithium-ion batteries: synthesis, electrochemical characterization and mechanical stabilization by block copolymerization
    Öppna denna publikation i ny flik eller fönster >>ε-Caprolactone-based solid polymer electrolytes for lithium-ion batteries: synthesis, electrochemical characterization and mechanical stabilization by block copolymerization
    Visa övriga...
    2018 (Engelska)Ingår i: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 8, nr 30, s. 16716-16725Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    In this work, three types of polymers based on epsilon-caprolactone have been synthesized: poly(epsilon-caprolactone), polystyrene-poly(epsilon-caprolactone), and polystyrene-poly(epsilon-caprolactone-r-trimethylene carbonate) (SCT), where the polystyrene block was introduced to improve the electrochemical and mechanical performance of the material. Solid polymer electrolytes (SPEs) were produced by blending the polymers with 10-40 wt% lithium bis(trifluoromethane) sulfonimide (LiTFSI). Battery devices were thereafter constructed to evaluate the cycling performance. The best performing battery half-cell utilized an SPE consisting of SCT and 17 wt% LiTFSI as both binder and electrolyte; a Li vertical bar SPE vertical bar LiFePO4 cell that cycled at 40 degrees C gave a discharge capacity of about 140 mA h g(-1) at C/5 for 100 cycles, which was superior to the other investigated electrolytes. Dynamic mechanical analysis (DMA) showed that the storage modulus E' was about 5 MPa for this electrolyte.

    Nationell ämneskategori
    Polymerkemi
    Identifikatorer
    urn:nbn:se:uu:diva-340854 (URN)10.1039/c8ra00377g (DOI)000431814500034 ()
    Forskningsfinansiär
    Energimyndigheten, 42031-1EU, Horisont 2020, 685716
    Tillgänglig från: 2018-02-04 Skapad: 2018-02-04 Senast uppdaterad: 2018-08-27Bibliografiskt granskad
    4. A Mechanical Robust yet highly Conductive Diblock Copolymer-based Solid Polymer Electrolyte for Room Temperature Structural Battery Applications
    Öppna denna publikation i ny flik eller fönster >>A Mechanical Robust yet highly Conductive Diblock Copolymer-based Solid Polymer Electrolyte for Room Temperature Structural Battery Applications
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Polymerkemi
    Identifikatorer
    urn:nbn:se:uu:diva-340855 (URN)
    Tillgänglig från: 2018-02-04 Skapad: 2018-02-04 Senast uppdaterad: 2018-02-04
  • 14.
    Bergfelt, Andreas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Lacey, Matthew J.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Hedman, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Sångeland, Christofer
    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.
    Bowden, Tim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    ε-Caprolactone-based solid polymer electrolytes for lithium-ion batteries: synthesis, electrochemical characterization and mechanical stabilization by block copolymerization2018Ingår i: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 8, nr 30, s. 16716-16725Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this work, three types of polymers based on epsilon-caprolactone have been synthesized: poly(epsilon-caprolactone), polystyrene-poly(epsilon-caprolactone), and polystyrene-poly(epsilon-caprolactone-r-trimethylene carbonate) (SCT), where the polystyrene block was introduced to improve the electrochemical and mechanical performance of the material. Solid polymer electrolytes (SPEs) were produced by blending the polymers with 10-40 wt% lithium bis(trifluoromethane) sulfonimide (LiTFSI). Battery devices were thereafter constructed to evaluate the cycling performance. The best performing battery half-cell utilized an SPE consisting of SCT and 17 wt% LiTFSI as both binder and electrolyte; a Li vertical bar SPE vertical bar LiFePO4 cell that cycled at 40 degrees C gave a discharge capacity of about 140 mA h g(-1) at C/5 for 100 cycles, which was superior to the other investigated electrolytes. Dynamic mechanical analysis (DMA) showed that the storage modulus E' was about 5 MPa for this electrolyte.

  • 15.
    Bergfelt, Andreas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Mogensen, Ronnie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Lacey, Matthew
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Guiomar, Hernández
    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.
    Bowden, Tim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Mechanically Robust and Highly Conductive Di-Block Copolymers as Solid Polymer Electrolytes for Room Temperature Li-ion Batteries2018Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Alternative solid polymer electrolytes (SPEs) hosts to the archetype poly(ethylene oxide) are gaining attention thanks to their appealing properties, such as higher cation transport number, thermal stability and electrochemical stability [1]. In addition, high mechanical stability is required in order to integrate easy-to-use materials into flexible or ‘structural’ batteries [2, 3].

     In this work, a solid polymer electrolyte (SPE) featuring high ionic conductivity and mechanical robustness at room temperature is presented. The SPE consists of a di-block copolymer, poly(benzyl methacrylate)-poly(ε-caprolactone-r-trimethylene carbonate) (BCT), mixed with different loadings of lithium bis(trifluoromethanesulfonyl)imide (LiTFSI). The highest ionic conductivity achieved for these SPEs was found with 16.7 wt% LiTFSI loading (BCT17), reaching 9.1 x 10-6 S cm-1 at 30 °C. The limited current fraction (F+) for the BCT17 electrolyte was calculated to be 0.64 with the Bruce-Vincent method. Furthermore, dynamic mechanical analysis showed a storage modulus (E’) of 0.2 GPa below 40 °C and 1 MPa above 50 °C. These results indicate that BCT with LiTFSI is a competitive electrolyte, combining high ionic conductivity and modulus at ambient temperatures.

     LiFePO4|BCT17|Li half-cells showed good cycling performance at 60 °C. At 30 °C, where the SPE possessed significantly higher modulus, decent cell performance could still be achieved after several optimization steps. These included incorporating a SPE as binder, and infiltration cast the SPE on the electrode to maximize the contact between both components, thereby improving the interfacial contact and decreasing the cell resistance and overpotential when cycling the battery device.

     References

    [1] J. Mindemark, M.J. Lacey, T. Bowden, D. Brandell. Prog Polym Sci, (2018). DOI: 10.1016/j.progpolymsci.2017.12.004.

    [2] J.F. Snyder, R.H. Carter, E.D. Wetzel. Chem Mater, 19 (2007) 3793-801.

    [3] W.S. Young, W.F. Kuan, Thomas H. Epps. J Polym Sci, Part B: Polym Phys, 52 (2014) 1-16.

  • 16.
    Bergfelt, Andreas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Mogensen, Ronnie
    Lacey, Matthew
    Hernández, Guiomar
    Brandell, Daniel
    Bowden, Tim
    A Mechanical Robust yet highly Conductive Diblock Copolymer-based Solid Polymer Electrolyte for Room Temperature Structural Battery ApplicationsManuskript (preprint) (Övrigt vetenskapligt)
  • 17.
    Bergfelt, Andreas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Rubatat, Laurent
    CNRS/UNIV Pau & Pays Adour, Institut des Sciences Analytiques et de Physico-Chimie pour l´ Environnement et les Materiaux, Pau, France.
    Brandell, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Bowden, Tim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Poly(benzyl methacrylate)-Poly[(oligo ethylene glycol) methyl ether methacrylate] Triblock-Copolymers as Solid Electrolyte for Lithium Batteries2018Ingår i: Solid State Ionics, ISSN 0167-2738, E-ISSN 1872-7689, Vol. 321, s. 55-61Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A triblock copolymer of benzyl methacrylate and oligo(ethylene glycol) methyl ether methacrylate was polymerized to form the general structure PBnMA-POEGMA-PBnMA, using atom transfer radical polymerization (ATRP). The block copolymer (BCP) was blended with lithium bis(trifluoro methylsulfonate) (LiTFSI) to form solid polymer electrolytes (SPEs). AC impedance spectroscopy was used to study the ionic conductivity of the SPE series in the temperature interval 30 °C to 90 °C. Small-angle X-ray scattering (SAXS) was used to study the morphology of the electrolytes in the temperature interval 30 °C to 150 °C. By using benzyl methacrylate as a mechanical block it was possible to tune the microphase separation by the addition of LiTFSI, as proven by SAXS. By doing so the ionic conductivity increased to values higher than ones measured on a methyl methacrylate triblock copolymer-based electrolyte in the mixed state, which was investigated in an earlier paper by our group. A Li|SPE|LiFePO4 half-cell was constructed and cycled at 60 °C. The cell produced a discharge capacity of about 100 mAh g−1 of LiFePO4 at C/10, and the half-cell cycled for more than 140 cycles.

  • 18.
    Bergfelt, Andreas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Rubatat, Laurent
    Univ Pau & Pays Adour, CNRS, Inst Sci Analyt & Physicochim Environm & Mat, UMR5254, F-64000 Pau, France.
    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.
    Bowden, Tim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    d8-poly(methyl methacrylate)-poly[(oligo ethylene glycol) methyl ether methacrylate] tri-block-copolymer electrolytes: Morphology, conductivity and battery performance2017Ingår i: Polymer, ISSN 0032-3861, E-ISSN 1873-2291, Vol. 131, s. 234-242Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A series of deuterated tri-block copolymers with the general structure d(8)-PMMA-POEGMA-d(8)-PMMA, with variation in d(8)-PMMA chain length, were synthesized using sequential controlled radical polymerization (ATRP). Solid polymer electrolytes (SPEs) were produced by blending tri-block copolymers and lithium bis(trifluoro methylsulfonate) (LiTFSI). Small-angle neutron scattering (SANS) was used to study the bulk morphology of the deuterated tri-block copolymer electrolyte series at 25 degrees C, 60 degrees C and 95 degrees C. The lack of a second T-g in DSC analysis together with modelling with the random phase approximation model (RPA) confirmed that the electrolytes are in the mixed state, with negative Flory-Huggins interaction parameters. AC impedance spectroscopy was used to study the ionic conductivity of the SPE series in the temperature interval 30 degrees C-90 degrees C, and a battery device was constructed to evaluate a 25 wt% d(8)-PMMA electrolyte. The Li | SPE | LiFePO4 cell cycled at 60 degrees C, giving a discharge capacity of 120 mAh g(-1), while cyclic voltammetry showed that the SPE was stable at 60 degrees C.

  • 19.
    Bergman, Martin
    et al.
    Chalmers, Dept Appl Phys, SE-41296 Gothenburg, Sweden..
    Bergfelt, Andreas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Sun, Bing
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Bowden, Tim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Brandell, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi. Uppsala Univ, Dept Chem, Angstrom Lab, SE-75121 Uppsala, Sweden..
    Johansson, Patrik
    Chalmers, Dept Appl Phys, SE-41296 Gothenburg, Sweden..
    Graft copolymer electrolytes for high temperature Li-battery applications, using poly(methyl methacrylate) grafted poly(ethylene glycol)methyl ether methacrylate and lithium bis(trifluoromethanesulfonimide)2015Ingår i: Electrochimica Acta, ISSN 0013-4686, E-ISSN 1873-3859, Vol. 175, s. 96-103Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    For successful hybridization of heavy vehicles, high temperature batteries might be the solution. Here, high temperature solid polymer electrolytes (SPE's) based on different ratios of poly(methyl methacrylate) (PMMA) and poly(ethylene glycol) methyl ether methacrylate (PEGMA), with LiTFSI salt (at a fixed ether oxygen (EO):Li ratio of 20:1) have been prepared and investigated. The copolymers comprise PMMA backbones with grafted PEGMA side-chains containing 9 EO units. The SPE systems were characterized using Raman spectroscopy, broadband dielectric spectroscopy, differential scanning calorimetry, thermal gravimetric analysis, and electrochemical cycling in prototype cells, with a particular focus on the 83 wt% PEGMA system. The electrolytes have good thermal stabilities and dissociate the LiTFSI salt easily, while at the same time maintaining low glass transition temperatures (T-g's). Depending on the polymeric structure, ionic conductivities >1 mS cm(-1) at 110 degrees C are detected, thus providing ion transport properties for a broad range of electrochemical applications. Prototype Li vertical bar polymer electrolyte vertical bar LiFePO4 cells utilizing the SPE at 60 degrees C showed surprisingly low capacities (<20 mA h g(-1) LiFePO4), which could be due to poor electrode/electrolyte contacts.

  • 20.
    Bermejo, Daniel
    et al.
    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.
    Tavares da Costa, Marcus Vinicius
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad mekanik.
    Podiyan, Oommen
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Gamstedt, E. Kristofer
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad mekanik.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Varghese, Oommen P.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    First Aldol-Crosslinked Hyaluronic Acid Hydrogel: Fast and Hydrolytically Stable Gel with Tissue Adhesive PropertiesIngår i: Chemical Sciences Journal, ISSN 2150-3494Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Currently, there are limited approaches to tailor 3D scaffolds crosslinked with a stable covalent C-C bond that does not require any catalysts or initiators. We present here the first hydrogels employing aldol condensation chemistry that exhibit exceptional physicochemical properties. We investigated the aldol-crosslinking chemistry using two types of aldehyde-modified hyaluronic acid (HA) derivatives, namely; an enolizable HA-aldehyde (HA-Eal) and a non-enolizable HA-aldehyde (HA-Nal). Hydrogels formed using HA-Eal demonstrate inferior crosslinking efficiency (due to intramolecular loop formation), when compared with hydrogels formed by mixing HA-Eal and HA-NaI leading to a cross-aldol product. The change in mechanical properties as a result of crosslinking at different pH is determined using rheological measurements and is interpreted in terms of molecular weight between cross-links (Mc). The novel HA cross-aldol hydrogels demonstrate excellent hydrolytic stability and favorable mechanical properties but allow hyaluronidase mediated enzymatic degradation. Interestingly, residual aldehyde functionality within the aldol product leads to adhesion to tissue as demonstrated by bonding two bone tissues. The aldehyde functionality also permits facile post-synthetic modifications with nucleophilic reagents such as Alexa FluorTM 488. Finally, we demonstrate that the novel hydrogel is biocompatible with encapsulated stem cells that show a linear rate of expansion in our 3–6 days of study.

  • 21.
    Bermejo-Velasco, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Insights into Covalent Chemistry for the Developmen­t of Biomaterials2019Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Covalent cross-linking chemistry is currently exploited in the preparation of biomaterial for biomedical applications. Choice of these chemistries for the preparation of biomaterials and bioconjugates strongly influences the biological output of these materials. Therefore, this thesis aims to develop novel bioconjugation strategies understanding their advantages and drawbacks. Our results provide new insight to adapt these chemical transformations for a specific application.

    The first part of this thesis points out the relevance of tuning different properties of biomaterials with specific emphasis on the development of hyaluronic acid (HA) hydrogels. The second part of the thesis describes how different chemical transformations including hydrazone formation (Paper I), thiazolidine formation (Paper II), cross-aldol addition reaction (Paper III) and disulfide formation (Paper IV) dictate material properties.

    This thesis explores both basic organic reaction mechanism and application of these reactions to influence material characteristics. The detailed study of the reaction conditions, kinetics, and stability of the products will help to understand the mechanical properties, hydrolytic stability, and degradability of the materials described here.

    Additionally, we performed degradation studies of gadolinium labeled HA hydrogels using magnetic resonance imaging. Furthermore, we also explored post-synthetic modification of hydrogels to link model fluorescent moieties as well as explored the tissue adhesive properties using Schiff-base formation.

    In summary, this thesis presents a selection of different covalent chemistries for the design of advanced biomaterials. The advantages and disadvantages of these chemistries are rigorously investigated. We believe, such an investigation provides a better understanding of the bioconjugation strategies for the preparation of biomaterials with potential clinical translation.

    Delarbeten
    1. Injectable hyaluronic acid hydrogels with the capacity for magnetic resonance imaging
    Öppna denna publikation i ny flik eller fönster >>Injectable hyaluronic acid hydrogels with the capacity for magnetic resonance imaging
    Visa övriga...
    2018 (Engelska)Ingår i: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 197, s. 641-648Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Monitoring hydrogel degradation in real time using noninvasive imaging techniques is of great interest for designing a scaffold in tissue engineering. We report the preparation of gadolinium (Gd)-labeled and injectable hyaluronic acid (HA) hydrogels that can be visualized using T-1- and T-2-weighted magnetic resonance imaging (MRI). An HA derivative functionalized with thiol and hydrazide was labeled using a diethylenetriaminepentaacetate complex modified with "clickable" dithiopyridyl functionalities (degree of modification was 3.77% with respect to HA repeat units). The HA derivative modified with cross-linkable groups and Gd complex exhibited relaxivities r(1) = 3.78 mM(-1)s(-1) and r(2) = 56.3 mM(-1)s(-1). A hydrazone hydrogel network was obtained by mixing Gd-labeled HA-hydrazide and HA-aldehyde derivatives. Enzymatic hydrogel degradation could be followed using MRI because the MR images showed great correlation with the hydrogel mass loss. Ex vivo MRI of injected Gd-labeled hydrogels demonstrated that they show a significant contrast difference (SNRcoronal = 456; SNRaxial = 459) from the surrounding tissues. These results indicate that our Gd-labeled HA hydrogel has great potential as an injectable biocompatible hydrogel that can be used for longitudinal tracking in vivo using MRI.

    Ort, förlag, år, upplaga, sidor
    ELSEVIER SCI LTD, 2018
    Nyckelord
    Gadolinium complex, Hyaluronic acid, Injectable hydrogels, Magnetic resonance imaging, Biodegradation
    Nationell ämneskategori
    Polymerkemi
    Identifikatorer
    urn:nbn:se:uu:diva-361020 (URN)10.1016/j.carbpol.2018.06.028 (DOI)000438466500070 ()30007657 (PubMedID)
    Tillgänglig från: 2018-09-20 Skapad: 2018-09-20 Senast uppdaterad: 2019-01-24
    2. Thiazolidine chemistry revisited: a fast, efficient and stable click-type reaction at physiological pH
    Öppna denna publikation i ny flik eller fönster >>Thiazolidine chemistry revisited: a fast, efficient and stable click-type reaction at physiological pH
    Visa övriga...
    2018 (Engelska)Ingår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 54, nr 88, s. 12507-12510Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    We describe the fast reaction kinetics between 1,2-aminothiols and aldehydes. Under physiological conditions such a click-type reaction afforded a thiazolidine product that remains stable and did not require any catalyst. This type of bioorthogonal reaction offers enormous potential for the coupling of biomolecules in an efficient and biocompatible manner.

    Nationell ämneskategori
    Polymerkemi
    Identifikatorer
    urn:nbn:se:uu:diva-364896 (URN)10.1039/c8cc05405c (DOI)000448947000019 ()30345438 (PubMedID)
    Tillgänglig från: 2018-11-06 Skapad: 2018-11-06 Senast uppdaterad: 2019-06-26Bibliografiskt granskad
    3. First Aldol-Crosslinked Hyaluronic Acid Hydrogel: Fast and Hydrolytically Stable Gel with Tissue Adhesive Properties
    Öppna denna publikation i ny flik eller fönster >>First Aldol-Crosslinked Hyaluronic Acid Hydrogel: Fast and Hydrolytically Stable Gel with Tissue Adhesive Properties
    Visa övriga...
    (Engelska)Ingår i: Chemical Sciences Journal, ISSN 2150-3494Artikel i tidskrift (Refereegranskat) Submitted
    Abstract [en]

    Currently, there are limited approaches to tailor 3D scaffolds crosslinked with a stable covalent C-C bond that does not require any catalysts or initiators. We present here the first hydrogels employing aldol condensation chemistry that exhibit exceptional physicochemical properties. We investigated the aldol-crosslinking chemistry using two types of aldehyde-modified hyaluronic acid (HA) derivatives, namely; an enolizable HA-aldehyde (HA-Eal) and a non-enolizable HA-aldehyde (HA-Nal). Hydrogels formed using HA-Eal demonstrate inferior crosslinking efficiency (due to intramolecular loop formation), when compared with hydrogels formed by mixing HA-Eal and HA-NaI leading to a cross-aldol product. The change in mechanical properties as a result of crosslinking at different pH is determined using rheological measurements and is interpreted in terms of molecular weight between cross-links (Mc). The novel HA cross-aldol hydrogels demonstrate excellent hydrolytic stability and favorable mechanical properties but allow hyaluronidase mediated enzymatic degradation. Interestingly, residual aldehyde functionality within the aldol product leads to adhesion to tissue as demonstrated by bonding two bone tissues. The aldehyde functionality also permits facile post-synthetic modifications with nucleophilic reagents such as Alexa FluorTM 488. Finally, we demonstrate that the novel hydrogel is biocompatible with encapsulated stem cells that show a linear rate of expansion in our 3–6 days of study.

    Nyckelord
    hyaluronic acid, aldol chemisty, stable hydrogels, tissue adhesive
    Nationell ämneskategori
    Materialkemi
    Forskningsämne
    Kemi med inriktning mot materialkemi
    Identifikatorer
    urn:nbn:se:uu:diva-374999 (URN)
    Tillgänglig från: 2019-01-24 Skapad: 2019-01-24 Senast uppdaterad: 2019-01-24
    4. Modulating thiol pKa promotes disulfide formation at physiological pH: An elegant strategy to design disulfide cross-linked hyaluronic acid hydrogels
    Öppna denna publikation i ny flik eller fönster >>Modulating thiol pKa promotes disulfide formation at physiological pH: An elegant strategy to design disulfide cross-linked hyaluronic acid hydrogels
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    2019 (Engelska)Ingår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 20, nr 3, s. 1412-1420Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The disulfide bond plays a crucial role in protein biology and has been exploited by scientists to develop antibody-drug conjugates, sensors and for the immobilization other biomolecules to materials surfaces. In spite of its versatile use, the disulfide chemistry suffers from some inevitable limitations such as the need for basic conditions (pH > 8.5), strong oxidants and long reaction times. We demonstrate here that thiol-substrates containing electron-withdrawing groups at the β-position influence the deprotonation of the thiol group, which is the key reaction intermediate in the formation of disulfide bonds. Evaluation of reaction kinetics using small molecule substrate such as L-cysteine indicated disulfide formation at a 2.8-fold higher (k1 = 5.04 x 10-4 min-1) reaction rate as compared to the conventional thiol substrate, namely 3-mercaptopropionic acid (k1 = 1.80 x 10-4 min-1) at physiological pH (pH 7.4). Interestingly, the same effect could not be observed when N-acetyl-L-cysteine substrate (k1 = 0.51 x 10-4 min-1) was used. We further grafted such thiol-containing molecules (cysteine, N-acetyl-cysteine, and 3-mercaptopropionic acid) to a biopolymer namely hyaluronic acid (HA) and determined the pKa value of different thiol groups by spectrophotometric analysis. The electron-withdrawing group at the β-position reduced the pKa of the thiol group to 7.0 for HA-cysteine (HA-Cys); 7.4 for N-acetyl cysteine (HA-ActCys) and 8.1 for HA-thiol (HA-SH) derivatives respectively. These experiments further confirmed that the concentration of thiolate (R-S-) ions could be increased with the presence of electron-withdrawing groups, which could facilitate disulfide cross-linked hydrogel formation at physiological pH. Indeed, HA grafted with cysteine or N-acetyl groups formed hydrogels within 3.5 minutes or 10 hours, respectively at pH 7.4. After completion of crosslinking reaction both gels demonstrated a storage modulus G’ ≈3300–3500 Pa, indicating comparable levels of crosslinking. The HA-SH gel, on the other hand, did not form any gel at pH 7.4 even after 24 h. Finally, we demonstrated that the newly prepared hydrogels exhibited excellent hydrolytic stability but can be degraded by cell-directed processes (enzymatic and reductive degradation). We believe our study provides a valuable insight on the factors governing the disulfide formation and our results are useful to develop strategies that would facilitate generation of stable thiol functionalized biomolecules or promote fast thiol oxidation according to the biomedical needs.

    Nationell ämneskategori
    Materialkemi
    Forskningsämne
    Kemi med inriktning mot materialkemi
    Identifikatorer
    urn:nbn:se:uu:diva-375001 (URN)10.1021/acs.biomac.8b01830 (DOI)000461270500028 ()30726668 (PubMedID)
    Forskningsfinansiär
    Stiftelsen för strategisk forskning (SSF), 139400127EU, FP7, Sjunde ramprogrammet, 607868Stiftelsen för strategisk forskning (SSF), 139400126
    Tillgänglig från: 2019-01-24 Skapad: 2019-01-24 Senast uppdaterad: 2019-04-11Bibliografiskt granskad
  • 22.
    Bermejo-Velasco, Daniel
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Azémar, Alice
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Oommen, Oommen P.
    Bioengineering and Nanomedicine Lab, Faculty of Medicine and Health Technologies and BioMediTech Institute, Tampere University, 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.
    Modulating thiol pKa promotes disulfide formation at physiological pH: An elegant strategy to design disulfide cross-linked hyaluronic acid hydrogels2019Ingår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 20, nr 3, s. 1412-1420Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The disulfide bond plays a crucial role in protein biology and has been exploited by scientists to develop antibody-drug conjugates, sensors and for the immobilization other biomolecules to materials surfaces. In spite of its versatile use, the disulfide chemistry suffers from some inevitable limitations such as the need for basic conditions (pH > 8.5), strong oxidants and long reaction times. We demonstrate here that thiol-substrates containing electron-withdrawing groups at the β-position influence the deprotonation of the thiol group, which is the key reaction intermediate in the formation of disulfide bonds. Evaluation of reaction kinetics using small molecule substrate such as L-cysteine indicated disulfide formation at a 2.8-fold higher (k1 = 5.04 x 10-4 min-1) reaction rate as compared to the conventional thiol substrate, namely 3-mercaptopropionic acid (k1 = 1.80 x 10-4 min-1) at physiological pH (pH 7.4). Interestingly, the same effect could not be observed when N-acetyl-L-cysteine substrate (k1 = 0.51 x 10-4 min-1) was used. We further grafted such thiol-containing molecules (cysteine, N-acetyl-cysteine, and 3-mercaptopropionic acid) to a biopolymer namely hyaluronic acid (HA) and determined the pKa value of different thiol groups by spectrophotometric analysis. The electron-withdrawing group at the β-position reduced the pKa of the thiol group to 7.0 for HA-cysteine (HA-Cys); 7.4 for N-acetyl cysteine (HA-ActCys) and 8.1 for HA-thiol (HA-SH) derivatives respectively. These experiments further confirmed that the concentration of thiolate (R-S-) ions could be increased with the presence of electron-withdrawing groups, which could facilitate disulfide cross-linked hydrogel formation at physiological pH. Indeed, HA grafted with cysteine or N-acetyl groups formed hydrogels within 3.5 minutes or 10 hours, respectively at pH 7.4. After completion of crosslinking reaction both gels demonstrated a storage modulus G’ ≈3300–3500 Pa, indicating comparable levels of crosslinking. The HA-SH gel, on the other hand, did not form any gel at pH 7.4 even after 24 h. Finally, we demonstrated that the newly prepared hydrogels exhibited excellent hydrolytic stability but can be degraded by cell-directed processes (enzymatic and reductive degradation). We believe our study provides a valuable insight on the factors governing the disulfide formation and our results are useful to develop strategies that would facilitate generation of stable thiol functionalized biomolecules or promote fast thiol oxidation according to the biomedical needs.

  • 23.
    Bermejo-Velasco, Daniel
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Dou, Weiqiang
    Radboud Univ Nijmegen, Med Ctr, Dept Radiol & Nucl Med, Nijmegen, Netherlands.
    Heerschap, Arend
    Radboud Univ Nijmegen, Med Ctr, Dept Radiol & Nucl Med, Nijmegen, Netherlands.
    Ossipov, Dmitri A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Hilborn, Jöns
    Uppsala Univ, Dept Chem, Angstrom Lab, Div Polymer Chem, Uppsala, Sweden.
    Injectable hyaluronic acid hydrogels with the capacity for magnetic resonance imaging2018Ingår i: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 197, s. 641-648Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Monitoring hydrogel degradation in real time using noninvasive imaging techniques is of great interest for designing a scaffold in tissue engineering. We report the preparation of gadolinium (Gd)-labeled and injectable hyaluronic acid (HA) hydrogels that can be visualized using T-1- and T-2-weighted magnetic resonance imaging (MRI). An HA derivative functionalized with thiol and hydrazide was labeled using a diethylenetriaminepentaacetate complex modified with "clickable" dithiopyridyl functionalities (degree of modification was 3.77% with respect to HA repeat units). The HA derivative modified with cross-linkable groups and Gd complex exhibited relaxivities r(1) = 3.78 mM(-1)s(-1) and r(2) = 56.3 mM(-1)s(-1). A hydrazone hydrogel network was obtained by mixing Gd-labeled HA-hydrazide and HA-aldehyde derivatives. Enzymatic hydrogel degradation could be followed using MRI because the MR images showed great correlation with the hydrogel mass loss. Ex vivo MRI of injected Gd-labeled hydrogels demonstrated that they show a significant contrast difference (SNRcoronal = 456; SNRaxial = 459) from the surrounding tissues. These results indicate that our Gd-labeled HA hydrogel has great potential as an injectable biocompatible hydrogel that can be used for longitudinal tracking in vivo using MRI.

  • 24.
    Bermejo-Velasco, Daniel
    et al.
    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.
    Tavares da Costa, Marcus Vinicius
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad mekanik.
    Oommen, Oommen P.
    Tampere Univ, Bioengn & Nanomed Lab, Fac Med & Hlth Technol, Korkeakoulunkatu 3, Tampere 33720, Finland;Tampere Univ, BioMediTech Inst, Korkeakoulunkatu 3, Tampere 33720, Finland.
    Gamstedt, E. Kristofer
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad mekanik.
    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.
    First Aldol Cross-Linked Hyaluronic Acid Hydrogel: Fast and Hydrolytically Stable Hydrogel with Tissue Adhesive Properties2019Ingår i: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 11, nr 41, s. 38232-38239Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Currently, there are limited approaches to tailor 3D scaffolds cross-linked with a stable covalent C-C bond that does not require any catalysts or initiators. We present here the first hydrogels employing aldol condensation chemistry that exhibit exceptional physicochemical properties. We investigated the aldol-cross-linking chemistry using two types of aldehyde-modified hyaluronic acid (HA) derivatives, namely, an enolizable HA-aldehyde (HA-EaI) and a non-enolizable HA-aldehyde (HA-NaI). Hydrogels formed using HA-EaI demonstrate inferior cross linking efficiency (due to intramolecular loop formation), when compared with hydrogels formed by mixing HA-EaI and HA-NaI leading to a cross-aldol product. The change in mechanical properties as a result of cross-linking at different pH values is determined using rheological measurements and is interpreted in terms of molecular weight between cross-links (Me). The novel HA cross-aldol hydrogel demonstrate excellent hydrolytic stability and favorable mechanical properties but allow hyaluronidase-mediated enzymatic degradation. Interestingly, residual aldehyde functionality within the aldol product rendered the tissue adhesive properties by bonding two bone tissues. The aldehyde functionality also facilitated facile post-synthetic modifications with nucleophilic reagents. Finally, we demonstrate that the novel hydrogel is biocompatible with encapsulated stem cells that show a linear rate of expansion in our 3-6 days of study.

  • 25.
    Bermejo-Velasco, Daniel
    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.
    Oommen, Oommen P.
    Bioengineering and Nanomedicine Lab, Faculty of Biomedical Sciences and Engineering, Tampere University of Technology, and BioMediTech Institute, 33720, Tampere, 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.
    Thiazolidine chemistry revisited: a fast, efficient and stable click-type reaction at physiological pH2018Ingår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 54, nr 88, s. 12507-12510Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We describe the fast reaction kinetics between 1,2-aminothiols and aldehydes. Under physiological conditions such a click-type reaction afforded a thiazolidine product that remains stable and did not require any catalyst. This type of bioorthogonal reaction offers enormous potential for the coupling of biomolecules in an efficient and biocompatible manner.

  • 26.
    Berts, Ida
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Fragneto, Giovanna
    Institut Laue-Langevin.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Rennie, Adrian R.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik.
    Tuning the density profile of surface-grafted hyaluronan and the effect of counter-ions2013Ingår i: European Physical Journal E, ISSN 1292-8941, Vol. 36, nr 7, s. 70-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The present paper investigates the structure and composition of grafted sodium hyaluronanat a solid-liquid interface using neutron reflection. The solvated polymer at the surface could be described with a density profile that decays exponentially towards the bulk solution. The density profileof the polymer varied depending on the deposition protocol. A single-stage deposition resulted in denser polymer layers, while layers created with a two-stage deposition process were more diffuse and had an overall lower density. Despite the diffuse density profile, two-stage deposition leads to a highersurface excess. Addition of calcium ions causes a strong collapse of the sodium hyaluronan chains, increasing the polymer density near the surface. This effect is more pronounced on the sample prepared by two-stage deposition due to the initial less dense profile. This study provides an understanding at a molecular level of how surface functionalization alters the structure and howsurface layers respond to changes in calcium ions in the solvent.

  • 27.
    Berts, Ida
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Inst Laue Langevin, 71 Ave Martyrs,CS 20156, F-38042 Grenoble, France..
    Fragneto, Giovanna
    Inst Laue Langevin, 71 Ave Martyrs,CS 20156, F-38042 Grenoble, France..
    Porcar, Lionel
    Inst Laue Langevin, 71 Ave Martyrs,CS 20156, F-38042 Grenoble, France..
    Hellsing, Maja S.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik. Uppsala Univ, Ctr Neutron Scattering, Box 516, S-75120 Uppsala, Sweden..
    Rennie, Adrian R.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik. Uppsala Univ, Ctr Neutron Scattering, Box 516, S-75120 Uppsala, Sweden..
    Controlling adsorption of albumin with hyaluronan on silica surfaces and sulfonated latex particles2017Ingår i: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 504, s. 315-324Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Polysaccharides are known to modify binding of proteins at interfaces and this paper describes studies of these interactions and how they are modified by pH. Specifically, the adsorption of human serum albumin on to polystyrene latex and to silica is described, focusing on how this is affected by hyaluronan. Experiments were designed to test how such binding might be modified under relevant physiological conditions. Changes in adsorption of albumin alone and the co-adsorption of albumin and hyaluronan are driven by electrostatic interactions. Multilayer binding is found to be regulated by the pH of the solution and the molecular mass and concentration of hyaluronan. Highest adsorption was observed at pH below 4.8 and for low molecular mass hyaluronan (<= 150 kDa) at concentrations above 2 mg ml(-1). On silica with grafted hyaluronan, albumin absorption is reversed by changes in solvent pH due to their strong electrostatic attraction. Albumin physisorbed on silica surfaces is also rinsed away with dilute hyaluronan solution at pH 4.8. The results demonstrate that the protein adsorption can be controlled both by changes of pH and by interaction with other biological macromolecules.

  • 28.
    Berts, Ida
    et al.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Gerelli, Yuri
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Rennie, Adrian R.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik.
    Structure of polymer and particle aggregates in hydrogel composites2013Ingår i: Journal of Polymer Science Part B: Polymer Physics, ISSN 0887-6266, E-ISSN 1099-0488, Vol. 51, nr 6, s. 421-429Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Knowledge of the structure of a biomaterial is usually vital to control its function. This article provides a structural characterization of a hyaluronan scaffold that has demonstrated good biocompatibility and is used to induce bone regeneration. Hyaluronan hydrogels are appealing materials that can function as a matrix to incorporate both organic and inorganic substances to enhance tissue growth. Because of the intrinsic properties of this swollen matrix, one needs a very sensitive technique that can be applied in situ to determine the organization of the polymers in a gel. Small-angle neutron scattering is used to determine the characteristics of the inhomogeneous structure of the hydrogel both with and without added particles. The results are interpreted using models of structure with two length scales that are beyond the traditional picture of homogeneous gels. The observed structure and the dimensions can explain the previously reported rheological properties of gels containing different amount of polymers. Hydroxyapatite nanoparticles added to the gel are frozen in the gel matrix. We are able to determine the distribution and shape of these particles as they aggregate around the polymer chains. We have also concluded, in this case, that the particle structure is concentration independent. Information about the nanostructure for an applicable biomaterial guides the formulation, preparation, and use that should lead to further understanding of its exploitation.

  • 29.
    Billström, Gry Hulsart
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Piskounova, Sonya
    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.
    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.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Improved bone formation by altering surface area of hyaluronan-based hydrogel carrier for bone morphogenetic protein-22012Ingår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, s. S114-S114Artikel i tidskrift (Övrigt vetenskapligt)
  • 30.
    Cantoni, Federico
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Johansson, Sofia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Pohlit, Hannah
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Porras, Ana Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik.
    Samanta, Ayan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Tenje, Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Mikrosystemteknik. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    2D and 3D patterning of biological hydrogels for organ-on-chip applications2018Konferensbidrag (Övrigt vetenskapligt)
  • 31.
    Chen, Song
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Shi, Liyang
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Hunan Univ, Coll Biol, Changsha 410082, Hunan, Peoples R China.
    Luo, Jun
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Novel Fast-Setting Mineral Trioxide Aggregate: Its Formulation, Chemical-Physical Properties, and Cytocompatibility2018Ingår i: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 10, nr 24, s. 20334-20341Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    One of the main drawbacks that limits the application of mineral trioxide aggregate (MTA) in dental field is its long setting time. Mineral trioxide aggregate with accelerated setting properties and excellent chemical-physical and biological properties is still required. In this study, an innovative mineral trioxide aggregate, which consists of calcium silicates, calcium aluminates, and zirconium oxide, was designed to obtain fast-setting property. The optimized formulation can achieve initial setting in 10 min and final setting in 15 min, which are much faster than commercial mineral trioxide aggregate. In addition, the optimized fast-setting MTA showed adequate radiopacity and good biocompatibility. The ion concentrations after storage in water for 1 day were 52.3 mg/L Ca, 67.7 mg/L Al, 48.8 mg/L Si, and 11.7 mg/L Mg. The hydration products of hardened cements were investigated by X-ray diffraction, scanning electron microscopy, and Fourier transform infrared, showing the accelerated setting time was due to the formation of honeycomb-like calcium silicate hydrate gel. The novel MTA could be a promising material for dental applications.

  • 32.
    Diba, Mani
    et al.
    Radboud Univ Nijmegen Med Ctr, Dept Biomat, NL-6525 EX Nijmegen, Netherlands..
    An, Jie
    Radboud Univ Nijmegen Med Ctr, Dept Biomat, NL-6525 EX Nijmegen, Netherlands..
    Schmidt, Stephan
    Heinrich Heine Univ Dusseldorf, Inst Organ & Macromol Chem, D-40225 Dusseldorf, Germany..
    Hembury, Mathew
    Univ Utrecht, Fac Sci, UIPS, Dept Pharmaceut, NL-3508 TB Utrecht, Netherlands..
    Ossipov, Dmitri
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Boccaccini, Aldo R.
    Univ Erlangen Nurnberg, Dept Mat Sci & Engn, Inst Biomat, D-91058 Erlangen, Germany..
    Leeuwenburgh, Sander C. G.
    Radboud Univ Nijmegen Med Ctr, Dept Biomat, NL-6525 EX Nijmegen, Netherlands..
    Exploiting Bisphosphonate-Bioactive-Glass Interactions for the Development of Self-Healing and Bioactive Composite Hydrogels2016Ingår i: Macromolecular rapid communications, ISSN 1022-1336, E-ISSN 1521-3927, Vol. 37, nr 23, s. 1952-1959Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hydrogels are widely recognized as promising candidates for various biomedical applications, such as tissue engineering. Recently, extensive research efforts have been devoted to the improvement of the biological and mechanical performance of hydrogel systems by incorporation of functional groups and/or inorganic particles in their composition. Bisphosphonates are a class of drugs, commonly used for treatment of osteoporosis, which exhibit a strong binding affinity for hydroxyapatite. In this study, the binding affinity of a bisphosphonate-functionalized polymer, hyaluronan, toward a bioactive glass (i.e., 45S5 Bioglass) is evaluated using force-distance measurements with atomic force microscopy. The strong interaction between bisphosphonate and bioactive glass is then exploited to develop organic-inorganic composite hydrogels and the viscoelastic and self-healing ability of these materials are investigated. Finally, the stability and mineralization behavior of these hydrogels are evaluated in simulated body fluid. Following this approach, injectable, bioactive and self-healing organic-inorganic composite hydrogels are produced, which mineralize abundantly and rapidly in simulated body fluid. These properties render these composite gels suitable for applications in bone-tissue engineering.

  • 33.
    Edin, Elle
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Composite Regenerative Scaffolds2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Regenerative medicine and tissue engineering solutions of heavily innervated tissues are at this point lacklustre. This thesis expands our knowledge of appropriate acellular scaffolds for tissue repair in general and nerve regeneration in particular. The optimal surgical procedure for the implantation of artificial extracellular matrix (ECM) was evaluated for recombinant human collagen (RHCIII) implants. Suturing techniques, as well as the usage of human amniotic membrane “bandages” were evaluated. While complete regeneration of corneal tissues occurred, only slight differences in effects of surgical technique could be found.

    The safety and efficacy of clinical trials using mesenchymal stromal cells (MSCs) was evaluated by conducting a systematic review and meta-analysis. MSC therapy was shown to be safe, with no increases mortality, rehospitalization or adverse events. There was also an indication of efficacy, as the overall mortality in the studies included was significantly smaller in the MSC treated group.

    Multicomponent hydrogel capsules encapsulating single cells were developed. Capsules manufactured from gelatin, agarose and fibrinogen were compared to pure gelatin capsules. The composite capsules successfully delayed cell release and prolonged cell survival.

    Surface patterning of collagen based biomimetic corneas was performed by microcontact printing. The ability of different sizes of fibronectin stripes to stimulate cell adhesion and proliferation was compared. The patterned surfaces improved cell adhesion, as well as proliferation markers.

    Conductive polymer composites were manufactured for use as nerve guides. The guides were created from electrospun polycaprolactone fibers coated with a series of different poly(3,4-ethylenedioxythiophene) films. A comparison of nerve progenitor growth and differentiation on the composite fibers was performed. Both the effects of fiber composition and MSC co-culture was investigated, with or without electrostimulation. MSC treatments and polymer coating was both important for nerve cell differentiation and growth.

    Delarbeten
    1. Effect of Surgical Technique on Corneal Implant Performance.
    Öppna denna publikation i ny flik eller fönster >>Effect of Surgical Technique on Corneal Implant Performance.
    Visa övriga...
    2014 (Engelska)Ingår i: Translational vision science & technology, ISSN 2164-2591, Vol. 3, nr 2, artikel-id 6Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    PURPOSE: Our aim was to determine the effect of a surgical technique on biomaterial implant performance, specifically graft retention.

    METHODS: Twelve mini pigs were implanted with cell-free, 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) cross-linked recombinant human collagen type III (RHCIII) hydrogels as substitutes for donor corneal allografts using overlying sutures with or without human amniotic membrane (HAM) versus interrupted sutures with HAM. The effects of the retention method were compared as well as the effects of collagen concentration (13.7% to 15% RHCIII).

    RESULTS: All implanted corneas showed initial haze that cleared with time, resulting in corneas with optical clarity matching those of untreated controls. Biochemical analysis showed that by 12 months post operation, the initial RHCIII implants had been completely remodeled, as type I collagen, was the major collagenous protein detected, whereas no RHCIII could be detected. Histological analysis showed all implanted corneas exhibited regeneration of epithelial and stromal layers as well as nerves, along with touch sensitivity and tear production. Most neovascularization was seen in corneas stabilized by interrupted sutures.

    CONCLUSIONS: This showed that the surgical technique used does have a significant effect on the overall performance of corneal implants, overlying sutures caused less vascularization than interrupted sutures.

    TRANSLATIONAL RELEVANCE: Understanding the significance of the suturing technique can aid the selection of the most appropriate procedure when implanting artificial corneal substitutes. The same degree of regeneration, despite a higher collagen content indicates that future material development can progress toward stronger, more resistant implants.

    Nyckelord
    biomaterials, biosynthetic cornea, corneal regeneration, corneal transplantation, recombinant human collagen
    Nationell ämneskategori
    Kirurgi
    Identifikatorer
    urn:nbn:se:uu:diva-364450 (URN)10.1167/tvst.3.2.6 (DOI)24749003 (PubMedID)
    Tillgänglig från: 2018-10-29 Skapad: 2018-10-29 Senast uppdaterad: 2018-10-29
    2. Conductive PEDOT based coatings on microfibrous scaffolds: a nerve guide component
    Öppna denna publikation i ny flik eller fönster >>Conductive PEDOT based coatings on microfibrous scaffolds: a nerve guide component
    Visa övriga...
    2018 (Engelska)Manuskript (preprint) (Övrig (populärvetenskap, debatt, mm))
    Nationell ämneskategori
    Biomaterialvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-364452 (URN)
    Tillgänglig från: 2018-10-29 Skapad: 2018-10-29 Senast uppdaterad: 2018-10-29
    3. Mesenchymal Stromal Cells for the Treatment of Ischemic Injury and Vascular Trauma: A Systematic Review and Meta-Analysis
    Öppna denna publikation i ny flik eller fönster >>Mesenchymal Stromal Cells for the Treatment of Ischemic Injury and Vascular Trauma: A Systematic Review and Meta-Analysis
    Visa övriga...
    2018 (Engelska)Manuskript (preprint) (Övrig (populärvetenskap, debatt, mm))
    Nationell ämneskategori
    Annan klinisk medicin
    Identifikatorer
    urn:nbn:se:uu:diva-364451 (URN)
    Tillgänglig från: 2018-10-29 Skapad: 2018-10-29 Senast uppdaterad: 2018-10-29
    4. Functional fabrication of recombinant human collagen-phosphorylcholine hydrogels for regenerative medicine applications.
    Öppna denna publikation i ny flik eller fönster >>Functional fabrication of recombinant human collagen-phosphorylcholine hydrogels for regenerative medicine applications.
    Visa övriga...
    2015 (Engelska)Ingår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 12, s. 70-80, artikel-id S1742-7061(14)00486-3Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The implant-host interface is a critical element in guiding tissue or organ regeneration. We previously developed hydrogels comprising interpenetrating networks of recombinant human collagen type III and 2-methacryloyloxyethyl phosphorylcholine (RHCIII-MPC) as substitutes for the corneal extracellular matrix that promote endogenous regeneration of corneal tissue. To render them functional for clinical application, we have now optimized their composition and thereby enhanced their mechanical properties. We have demonstrated that such optimized RHCIII-MPC hydrogels are suitable for precision femtosecond laser cutting to produce complementing implants and host surgical beds for subsequent tissue welding. This avoids the tissue damage and inflammation associated with manual surgical techniques, thereby leading to more efficient healing. Although we previously demonstrated in clinical testing that RHCIII-based implants stimulated cornea regeneration in patients, the rate of epithelial cell coverage of the implants needs improvement, e.g. modification of the implant surface. We now show that our 500μm thick RHCIII-MPC constructs comprising over 85% water are suitable for microcontact printing with fibronectin. The resulting fibronectin micropatterns promote cell adhesion, unlike the bare RHCIII-MPC hydrogel. Interestingly, a pattern of 30μm wide fibronectin stripes enhanced cell attachment and showed the highest mitotic rates, an effect that potentially can be utilized for faster integration of the implant. We have therefore shown that laboratory-produced mimics of naturally occurring collagen and phospholipids can be fabricated into robust hydrogels that can be laser profiled and patterned to enhance their potential function as artificial substitutes of donor human corneas.

    Nyckelord
    Collagen, Cornea, Hydrogel, Laser profiling, Surface modification
    Nationell ämneskategori
    Biomaterialvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-364449 (URN)10.1016/j.actbio.2014.10.035 (DOI)25448347 (PubMedID)
    Tillgänglig från: 2018-10-29 Skapad: 2018-10-29 Senast uppdaterad: 2018-10-29
    5. Controlled Delivery of Human Cells by Temperature Responsive Microcapsules.
    Öppna denna publikation i ny flik eller fönster >>Controlled Delivery of Human Cells by Temperature Responsive Microcapsules.
    Visa övriga...
    2015 (Engelska)Ingår i: Journal of Functional Biomaterials, ISSN 2079-4983, E-ISSN 2079-4983, Vol. 6, nr 2, s. 439-53Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Cell therapy is one of the most promising areas within regenerative medicine. However, its full potential is limited by the rapid loss of introduced therapeutic cells before their full effects can be exploited, due in part to anoikis, and in part to the adverse environments often found within the pathologic tissues that the cells have been grafted into. Encapsulation of individual cells has been proposed as a means of increasing cell viability. In this study, we developed a facile, high throughput method for creating temperature responsive microcapsules comprising agarose, gelatin and fibrinogen for delivery and subsequent controlled release of cells. We verified the hypothesis that composite capsules combining agarose and gelatin, which possess different phase transition temperatures from solid to liquid, facilitated the destabilization of the capsules for cell release. Cell encapsulation and controlled release was demonstrated using human fibroblasts as model cells, as well as a therapeutically relevant cell line-human umbilical vein endothelial cells (HUVECs). While such temperature responsive cell microcapsules promise effective, controlled release of potential therapeutic cells at physiological temperatures, further work will be needed to augment the composition of the microcapsules and optimize the numbers of cells per capsule prior to clinical evaluation.

    Nyckelord
    cell delivery, cell encapsulation, human fibroblast, human umbilical vein endothelial cells, hydrogel, microcapsules, temperature responsive
    Nationell ämneskategori
    Biomaterialvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-364448 (URN)10.3390/jfb6020439 (DOI)26096147 (PubMedID)
    Tillgänglig från: 2018-10-29 Skapad: 2018-10-29 Senast uppdaterad: 2018-10-29
  • 34.
    Eimont, R.
    et al.
    Ferentis UAB, Savanorių 231, LT-02300, Vilnius, Lithuania; Department of Nanoengineering, Center for Physical Sciences and Technology, Savanorių 231, LT-02300, Vilnius, Lithuania.
    Vailionytė, A.
    Ferentis UAB, Savanorių 231, LT-02300, Vilnius, Lithuania; Department of Nanoengineering, Center for Physical Sciences and Technology, Savanorių 231, LT-02300, Vilnius, Lithuania.
    Cėpla, V.
    Ferentis UAB, Savanorių 231, LT-02300, Vilnius, Lithuania; Department of Nanoengineering, Center for Physical Sciences and Technology, Savanorių 231, LT-02300, Vilnius, Lithuania.
    Druceikaitė, K.
    Ferentis UAB, Savanorių 231, LT-02300, Vilnius, Lithuania.
    Inokaitis, H.
    Institute of Anatomy, Lithuanian University of Health Sciences, Mickeviciaus 9, LT-43074, Kaunas, Lithuania.
    Dabkevičiūtė, L.
    Laboratory of Molecular Neurobiology, Neuroscience institute, Lithuanian University of Heath Sciences, Eiveniu 4, LT50161, Kaunas, Lithuania.
    Sukackaitė, E.
    Laboratory of Molecular Neurobiology, Neuroscience institute, Lithuanian University of Heath Sciences, Eiveniu 4, LT50161, Kaunas, Lithuania.
    Masilionis, I.
    Ferentis UAB, Savanorių 231, LT-02300, Vilnius, Lithuania; Department of Nanoengineering, Center for Physical Sciences and Technology, Savanorių 231, LT-02300, Vilnius, Lithuania.
    Ulčinas, A.
    Department of Nanoengineering, Center for Physical Sciences and Technology, Savanorių 231, LT-02300, Vilnius, Lithuania.
    Samanta, Ayan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Valiokas, R.
    Ferentis UAB, Savanorių 231, LT-02300, Vilnius, Lithuania; Department of Nanoengineering, Center for Physical Sciences and Technology, Savanorių 231, LT-02300, Vilnius, Lithuania.
    Jekabsone, A.
    Laboratory of Molecular Neurobiology, Neuroscience institute, Lithuanian University of Heath Sciences, Eiveniu 4, LT50161, Kaunas, Lithuania.
    Extracellular matrix mimetics by crosslinked peptide hydrogels: application to neural 3D cell cultures2018Ingår i: International conference Vita Scientia Conference book, 2018, s. 59-59Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Self-supporting, shapeable hydrogels that consist of self-assembling synthetic peptides mimic the structural blocks of the extracellular matrix (ECM). Although they have been developed for regenerative medicine purposes, with a potential of grafting into patients without transplantation from organ donors, this class of materials are attractive as scaffolds for advanced cell culture/ in vitro tissue applications. In the present study, we have combined a series of peptides with functional motives (collagen, fibronectin, and laminin-like) for promoting granule layer-like organization of primary cerebellar cells and for controlling the cell attachment, neuritogenesis, cluster size and organization. We show that the micro/nanofabricated hydrogel scaffolds are applicable as multiwell plate inserts helping to analyse cell migration, differentiation, proliferation, adhesion, ultimately forming organotypic cell culture and artificial tissue structures.

  • 35.
    Ekdahl, Kristina N
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Fromell, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Nilsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    The innate immunity response: A key factor in biocompatibility2017Ingår i: Bioresorbable Polymers for Biomedical Applications: From Fundamentals to Translational Medicine / [ed] Giuseppe Perale & Jöns Hilborn, Elsevier, 2017, s. 85-94Kapitel i bok, del av antologi (Refereegranskat)
  • 36.
    Ekdahl, Kristina N
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Linnaeus Univ, Linnaeus Ctr Biomat Chem, SE-39182 Kalmar, Sweden.
    Soveri, Inga
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Fellström, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Njurmedicin.
    Nilsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Cardiovascular disease in haemodialysis: role of the intravascular innate immune system.2017Ingår i: Nature Reviews Nephrology, ISSN 1759-5061, E-ISSN 1759-507X, Vol. 13, nr 5, s. 285-296Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Haemodialysis is a life-saving renal replacement modality for end-stage renal disease, but this therapy also represents a major challenge to the intravascular innate immune system, which is comprised of the complement, contact and coagulation systems. Chronic inflammation is strongly associated with cardiovascular disease (CVD) in patients on haemodialysis. Biomaterial-induced contact activation of proteins within the plasma cascade systems occurs during haemodialysis and initially leads to local generation of inflammatory mediators on the biomaterial surface. The inflammation is spread by soluble activation products and mediators that are generated during haemodialysis and transported in the extracorporeal circuit back into the patient together with activated leukocytes and platelets. The combined effect is activation of the endothelium of the cardiovascular system, which loses its anti-thrombotic and anti-inflammatory properties, leading to atherogenesis and arteriosclerosis. This concept suggests that maximum suppression of the intravascular innate immune system is needed to minimize the risk of CVD in patients on haemodialysis. A potential approach to achieve this goal is to treat patients with broad-specificity systemic drugs that target more than one of the intravascular cascade systems. Alternatively, 'stealth' biomaterials that cause minimal cascade system activation could be used in haemodialysis circuits.

  • 37.
    Engstrand, Johanna
    et al.
    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.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Polymers influencing the strength of injectable calcium phosphate bone cements-a preliminary study2012Ingår i: 22nd Interdisciplinary Research Conference on Biomaterials May 10th -12th, 2012, Uppsala, Swden.European Cells and Materials Vol 23 Suppl 3 2012 (page 32), 2012, s. 32-Konferensbidrag (Refereegranskat)
  • 38. Engstrand, Thomas
    et al.
    Kihlstrom, Lars
    Neovius, Erik
    Skogh, Ann-Charlott Docherty
    Lundgren, T. Kalle
    Jacobsson, Hans
    Bohlin, Jan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Åberg, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Development of a bioactive implant for repair and potential healing of cranial defects2014Ingår i: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 120, nr 1, s. 273-277Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The repair of complex craniofacial bone defects is challenging and a successful result is dependent on the size of the defect, quality of the soft tissue covering the defect, and choice of reconstruction method. The objective of this study was to develop a bioactive cranial implant that could provide a permanent reconstructive solution to the patient by stimulating bone healing of the defect. In this paper the authors report on the feasibility and clinical results of using such a newly developed device for the repair of a large traumatic and therapy-resistant cranial bone defect. The patient had undergone numerous attempts at repair, in which established methods had been tried without success. A mosaic-designed device was manufactured and implanted, comprising interconnected ceramic tiles with a defined calcium phosphate composition. The clinical outcome 30 months after surgery revealed a restored cranial vault without postoperative complications. Computed tomography demonstrated signs of bone ingrowth. Examination with combined 18F-fluoride PET and CT provided further evidence of bone healing of the cranial defect.

  • 39.
    Eriksson, Therese
    et al.
    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, Polymerkemi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Yue, Ma
    School of Materials Science and Engineering, Center for Nano Energy materials, Northwestern Polytechnical University, Youyi west road 127, Xi'an, China.
    Brandell, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Nanoparticle Additives in Poly(ε-Caprolactone)-Based Solid PolymerElectrolytes; Towards Lower Crystallinity and Higher Ionic Conductivity.2018Konferensbidrag (Refereegranskat)
  • 40. Ferreira, Silvia A
    et al.
    Motwani, Meghna S
    Faull, Peter A
    Seymour, Alexis J
    Yu, Tracy T L
    Enayati, Marjan
    Taheem, Dheraj K
    Salzlechner, Christoph
    Haghighi, Tabasom
    Kania, Ewa M
    Oommen, Oommen P
    Ahmed, Tarek
    Loaiza, Sandra
    Parzych, Katarzyna
    Dazzi, Francesco
    Varghese, Oommen P.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Festy, Frederic
    Grigoriadis, Agamemnon E
    Auner, Holger W
    Snijders, Ambrosius P
    Bozec, Laurent
    Gentleman, Eileen
    Bi-directional cell-pericellular matrix interactions direct stem cell fate2018Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, nr 1, artikel-id 4049Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Modifiable hydrogels have revealed tremendous insight into how physical characteristics of cells' 3D environment drive stem cell lineage specification. However, in native tissues, cells do not passively receive signals from their niche. Instead they actively probe and modify their pericellular space to suit their needs, yet the dynamics of cells' reciprocal interactions with their pericellular environment when encapsulated within hydrogels remains relatively unexplored. Here, we show that human bone marrow stromal cells (hMSC) encapsulated within hyaluronic acid-based hydrogels modify their surroundings by synthesizing, secreting and arranging proteins pericellularly or by degrading the hydrogel. hMSC's interactions with this local environment have a role in regulating hMSC fate, with a secreted proteinaceous pericellular matrix associated with adipogenesis, and degradation with osteogenesis. Our observations suggest that hMSC participate in a bi-directional interplay between the properties of their 3D milieu and their own secreted pericellular matrix, and that this combination of interactions drives fate.

  • 41.
    Fredriksson, Fanny
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Barnkirurgi.
    Engstrand, Thomas
    Christofferson, Rolf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Barnkirurgi.
    Bowden, Tim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Lilja, Helene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Barnkirurgi.
    Sutures impregnated with an aldehyde-carbonyl scavenger reduce peritoneal adhesionsArtikel i tidskrift (Refereegranskat)
  • 42.
    Fredriksson, Fanny
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnkirurgisk forskning.
    Sellberg, Felix
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Bowden, Tim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Engstrand, T.
    Karolinska Univ Hosp, Dept Reconstruct Plast Surg, SE-17176 Stockholm, Sweden.;Karolinska Inst, SE-17176 Stockholm, Sweden..
    Berglund, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Engstrand Lilja, Helene
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnkirurgisk forskning.
    Sutures impregnated with carbazate-activated polyvinyl alcohol reduce intraperitoneal adhesions2017Ingår i: Journal of Pediatric Surgery, ISSN 0022-3468, E-ISSN 1531-5037, Vol. 52, nr 11, s. 1853-1858Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Intraperitoneal adhesions cause significant morbidity. They occur after peritoneal trauma, which induces oxidative stress with production of inflammatory cytokines, peroxidized proteins (carbonyls) and lipids (aldehydes). This study aimed to investigate if carbazate-activated polyvinyl alcohol (PVAC), an aldehyde-carbonyl inhibitor, can reduce intraperitoneal adhesions in an experimental model.

    Material and methods: Male Sprague-Dawley rats (n = 110) underwent laparotomy, cecal abrasion and construction of a small bowel anastomosis. They either were treated with intraperitoneal instillation of PVAC or were sutured with PVAC-impregnated sutures. Thromboelastography analysis was performed using human blood and PVAC. The lipid peroxidation product malondialdehyde (MDA) and inflammatory cytokines IL-1 beta and IL-6 were quantified in peritoneal fluid. At day 7, bursting pressure of the anastomosis was measured and adhesions were blindly scored.

    Results: PVAC in human blood decreased the production of the fibrin-thrombocyte mesh without affecting the coagulation cascade. MDA, IL-1 beta and IL-6 were increased after 6 h without significant difference between the groups. PVAC-impregnated sutures reduced intraperitoneal adhesions compared to controls (p = 0.0406) while intraperitoneal instillation of PVAC had no effect. Anastomotic bursting pressure was unchanged.

    Conclusions: Intervention with an aldehyde-carbonyl inhibitor locally in the wound by PVAC-impregnated sutures might be a new strategy to reduce intraperitoneal adhesions.

  • 43.
    Griffith, May
    et al.
    Prasad Eye Institute (LVPEI), Kallam Anji Reddy Campus, L V Prasad Marg, Banjara Hills, Hyderabad, Telangana 500034 (IN).
    Samanta, Ayan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Prasad Eye Institute (LVPEI), Kallam Anji Reddy Campus, L V Prasad Marg, Banjara Hills, Hyderabad, Telangana 500034 (IN).
    Jangamreddy, Jaganmohan Reddy
    Prasad Eye Institute (LVPEI), Kallam Anji Reddy Campus, L V Prasad Marg, Banjara Hills, Hyderabad, Telangana 500034 (IN).
    COLLAGEN AND COLLAGEN LIKE PEPTIDE BASED HYDROGELS, CORNEAL IMPLANTS, FILLER GLUE AND USES THEREOF2018Patent (Övrig (populärvetenskap, debatt, mm))
    Abstract [en]

    The present invention provides for collagen and collagen like peptide based hydrogels, corneal implants, filler glue 00 and uses thereof. The invention represents an advancement in the field of hydrogels, corneal implants, filler glue based on collagen o and collagen like peptides. The invention discloses collagen and novel collagen like peptides crosslinked with DMTMM and their use in preparation of hydrogel, corneal implant and filler glue which are highly efficacious and robust as compared to existing corneal implants. Further, the invention relates to method of treating corneal defects and diseases.

  • 44.
    Gurav, Deepanjali
    et al.
    Savitri Bai Phule Pune Univ, Dept Chem, Pune, Maharashtra, India..
    Varghese, Oommen P.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Hamad, Osama A.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Nilsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Hilborn, Jöns
    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.
    Chondroitin sulfate coated gold nanoparticles: a new strategy to resolve multidrug resistance and thromboinflammation2016Ingår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 52, nr 5, s. 966-969Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have developed the first chondroitin sulfate polymer coated gold nanoparticles that can simultaneously overcome mulidrug resistance in cancer cells and suppress thromboinflammation triggered by the chemotherapeutic drug.

  • 45.
    Han, Yuanyuan
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Li, Hu
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Jafri, Syed Hassan Mujtaba
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Fasta tillståndets fysik.
    Ossipov, Dmitri A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    LEIFER, KLAUS
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Fasta tillståndets elektronik.
    Graphene Based Mechanical Biosensor by Employing Non-covalent Stacking Functionalization2019Ingår i: Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Herein we demonstrate a novel methodology to achieve mechanical biosensor by employing the distinguished interaction forces between the atomic force microscope (AFM) probe and sensor surfaces as the response signal. This mechanical biosensor is fabricated by utilizing the non-covalent π-π stacking of pyrene-maltose onto graphene surfaces with Concanavalin A (Con A) as a target protein. The atomic resolution scanning tunneling microscopy (STM) images indicate the successful formation of the self-assembled and densely packed pyrene-maltose layer on the sensor surface, which gives distinct atomic lattice structure as compared to pristine graphene. This mechanical biosensor exhibits detection of Con A with the sensitivity down to nanomolar level. Therefore, this proposed mechanical biosensor has the potential to be employed in a variety of bio-sensing applications.

  • 46.
    Han, Yuanyuan
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Qiu, Zhen
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Fasta tillståndets fysik.
    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.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Tian, Bo
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Fasta tillståndets fysik. Tech Univ Denmark, Dept Micro & Nanotechnol, DK-2800 Kongens Lyngby, Denmark.
    Leifer, Klaus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    MicroRNA detection based on duplex-specific nuclease-assisted target recycling and gold nanoparticle/graphene oxide nanocomposite-mediated electrocatalytic amplification2019Ingår i: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 127, s. 188-193Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    DNA technology based bio-responsive nanomaterials have been widely studied as promising tools for biomedical applications. Gold nanoparticles (AuNPs) and graphene oxide (GO) sheets are representative zero- and two-dimensional nanomaterials that have long been combined with DNA technology for point-of-care diagnostics. Herein, a cascade amplification system based on duplex-specific nuclease (DSN)-assisted target recycling and electrocatalytic water-splitting is demonstrated for the detection of microRNA. Target microRNAs can form DNA: RNA heteroduplexes with DNA probes on the surface of AuNPs, which can be hydrolyzed by DSN. MicroRNAs are preserved during the reaction and released into the suspension for the digestion of multiple DNA probes. After the DSN-based reaction, AuNPs are collected and mixed with GO to form AuNP/GO nanocomposite on an electrode for the following electrocatalytic amplification. The utilization of AuNP/GO nanocomposite offers large surface area, exceptional affinity to water molecules, and facilitated mass diffusion for the water-splitting reaction. For let-7b detection, the proposed biosensor achieved a limit detection of 1.5 fM in 80 min with a linear detection range of approximately four orders of magnitude. Moreover, it has the capability of discriminating non-target microRNAs containing even single-nucleotide mismatches, thus holding considerable potential for clinical diagnostics.

  • 47.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Evaluation of biomaterials derived from ecm components2014Ingår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, s. 12-12Artikel i tidskrift (Övrigt vetenskapligt)
  • 48.
    Hilborn, Jöns
    et al.
    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.
    Jeronimo, B.
    Keynote: Safe and efficient in-vivo gene gene transfer and silencing technologies using natural pathways2012Ingår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, Vol. 6, nr suppl 1, s. 190-190Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Introduction: The advance in nucleic acids therapeutic had been outstanding in recent years, which have opened new possibilities in regenerative medicine to tackle many serious diseases. To make nucleic acids based therapy a reality, the fundamental problem of tissue specific cellular delivery has to be accomplished. Here we present a new approach to develop the next generation of delivery vectors.

    Materials and methods: Hyaluronic acid were modified to complex DNA plasmids for luciferase transfection. Transfection: HCT 116 cells and mice where tranfected by adding HA-DNA complex. The transfection experiment with commercially available reagent polyethyleneimine (PEI) and plasmid alone were used as controls.

    Results and discussion: Efficient tranfection was shown using the new non toxic and safe non viral vector. Using ECM components (such as hyaluronic acid or HA) that allow both in vitroandin vivo transfection of plasmid DNA in CD44 positive cells. The chemically modified ECM components (non-toxic) binds to nucleic acids and are taken in by cells by natural receptor mediated endocytosis. The amount transported via these routes naturally is around 10 gram per day to give a potential capacity far exceeding the need for transfection if it is targeted. By molecular association strategies (joining the bandwagon) it is now possible for nucleic acids to follow these pathways that utilise the highly efficient receptor mediated endocytosis- door opener into cells.

  • 49.
    Hilborn, Jöns
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Zhang, Yu
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Heher, P.
    Wolbank, S.
    Redl, H.
    Ossipov, Dmitri
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Fibrin-hyaluronic acid interpenetrating double network with improved fibrin stability by simultaneous and orthogonal enzymatic and disulfide cross-linking2014Ingår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, s. 150-150Artikel i tidskrift (Övrigt vetenskapligt)
  • 50. Hoogenkamp, Henk R.
    et al.
    Koens, Martin J. W.
    Geutjes, Paul J.
    Ainoedhofer, Herwig
    Wanten, Geert
    Tiemessen, Dorien M.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Gupta, Bhuvanesh
    Feitz, Wouter F. J.
    Daamen, Willeke F.
    Saxena, Amulya K.
    Oosterwijk, Egbert
    van Kuppevelt, Toin H.
    Seamless Vascularized Large-Diameter Tubular Collagen Scaffolds Reinforced with Polymer Knittings for Esophageal Regenerative Medicine2014Ingår i: Tissue Engineering. Part C, Methods, ISSN 1937-3384, E-ISSN 1937-3392, Vol. 20, nr 5, s. 423-430Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A clinical demand exists for alternatives to repair the esophagus in case of congenital defects, cancer, or trauma. A seamless biocompatible off-the-shelf large-diameter tubular scaffold, which is accessible for vascularization, could set the stage for regenerative medicine of the esophagus. The use of seamless scaffolds eliminates the error-prone tubularization step, which is necessary when emanating from flat scaffolds. In this study, we developed and characterized three different types of seamless tubular scaffolds, and evaluated in vivo tissue compatibility, including vascularization by omental wrapping. Scaffolds (luminal O approximate to 1.5cm) were constructed using freezing, lyophilizing, and cross-linking techniques and included (1) single-layered porous collagen scaffold, (2) dual-layered (porous+dense) collagen scaffold, and (3) hybrid scaffold (collagen+incorporated polycaprolacton knitting). The latter had an ultimate tensile strength comparable to a porcine esophagus. To induce rapid vascularization, scaffolds were implanted in the omentum of sheep using a wrapping technique. After 6 weeks of biocompatibility, vascularization, calcification, and hypoxia were evaluated using immunohistochemistry. Scaffolds were biocompatible, and cellular influx and ingrowth of blood vessels were observed throughout the whole scaffold. No calcification was observed, and slight hypoxic conditions were detected only in the direct vicinity of the polymer knitting. It is concluded that seamless large-diameter tubular collagen-based scaffolds can be constructed and vascularized in vivo. Such scaffolds provide novel tools for esophageal reconstruction.

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