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  • 1.
    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-22012Inngår i: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 50, s. S114-S114Artikkel i tidsskrift (Annet vitenskapelig)
  • 2.
    Forsgren, Johan
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Brohede, Ulrika
    Sandvik AB, Stockholm.
    Piskounova, Sonya
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Mihranyan, Albert
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Maria, Strømme
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    In Vivo Evaluation of Functionalized Biomimetic Hydroxyapatite for Local Delivery of Active Agents2011Inngår i: Journal of Biomaterials and Nanobiotechnology, ISSN 2158-7027, 2158-7043, Vol. 2, nr 2, s. 149-154Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study was carried out to investigate the biological response in vivo to biomimetic hydroxyapatite implant coatings functionalized with bisphosphonates and bone morphogenetic proteins. The functionalization was carried out by a simple soaking procedure in the operating room immediately prior to surgery. Cylindrical titanium samples with and without coatings were implanted in the distal femoral epiphysis of sheep and retrieved after 6 weeks. The histological analysis proved that all samples were integrated well in the tissue with no signs of intolerance. Fewer osteoclasts were observed in the vicinity of bisphosphonate-functionalized samples and the bone was denser around these samples compared to the other samples. Samples functionalized with bone morphogenetic protein induced more bone/implant contact but showed a more inconsistent outcome with reduced bone density around the samples. This study demonstrates a simple method to functionalize implant coatings, which provides surgeons with an option of patient-specific functionalization of implants. The observed biological impact due to the delivery of active molecules from the coatings suggests that this strategy may also be employed to deliver antibiotics from similar coatings.

  • 3.
    Hulsart-Billström, Gry
    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.
    Andersson, Britt-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bergman, Kristoffer
    Hilborn, Jöns
    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.
    Bowden, Tim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Morphological differences in BMP-2-induced ectopic bone between solid and crushed hyaluronan hydrogel templates2013Inngår i: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 24, nr 5, s. 1201-1209Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The possibility to affect bone formation by using crushed versus solid hydrogels as carriers for bone morphogenetic protein 2 (BMP-2) was studied. Hydrogels, based on chemical crosslinking between hyaluronic acid and poly(vinyl alcohol) derivatives, were loaded with BMP-2 and hydroxyapatite. Crushed and solid forms of the gels were analyzed both in vitro via a release study using I-125 radioactive labeling of BMP-2, and in vivo in a subcutaneous ectopic bone model in rats. Dramatically different morphologies were observed for the ectopic bone formed in vivo in the two types of gels, even though virtually identical release profiles were observed in vitro. Solid hydrogels induced formation of a dense bone shell around non-degraded hydrogel, while crushed hydrogels demonstrated a uniform bone formation throughout the entire sample. These results suggest that by crushing the hydrogel, the construct's three-dimensional network becomes disrupted. This could expose unreacted functional groups, making the fragment's surfaces reactive and enable limited chemical fusion between the crushed hydrogel fragments, leading to similar in vitro release profiles. However, in vivo these interactions could be broken by enzymatic activity, creating a macroporous structure that allows easier cell infiltration, thus, facilitating bone formation.

  • 4.
    Ossipov, Dmitri A.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Piskounova, Sonya
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Varghese, Oommen P.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Functionalization of Hyaluronic Acid with Chemoselective Groups via a Disulfide-Based Protection Strategy for In Situ Formation of Mechanically Stable Hydrogels2010Inngår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 11, nr 9, s. 2247-2254Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 5.
    Piskounova, Sonya
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Biomaterials for Promoting Self-Healing of Bone Tissue2011Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

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

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

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

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

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

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

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

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

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

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

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

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

  • 7.
    Piskounova, Sonya
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Gedda, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap.
    Hulsart-Billström, Gry
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Bowden, Tim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Characterization of recombinant human bone morphogenetic protein-2 delivery from injectable hyaluronan-based hydrogels by means of I-125-radiolabelling2014Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, nr 10, s. 821-830Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 8.
    Piskounova, Sonya
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Rojas, Ramiro
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Bergman, Kristoffer
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för materialkemi, Polymerkemi.
    The Effect of Mixing on the Mechanical Properties of Hyaluronan-Based Injectable Hydrogels2011Inngår i: Macromolecular materials and engineering (Print), ISSN 1438-7492, E-ISSN 1439-2054, Vol. 296, nr 10, s. 944-951Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 9.
    Stenfelt, Sonya
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Medicinsk utvecklingsbiologi.
    Blixt, Maria K. E.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    All-Ericsson, Charlotta
    S T Eriks Ogonsjukhus, Karolinska Inst, Stockholm, Sweden..
    Hallböök, Finn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Medicinsk utvecklingsbiologi.
    Boije, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Medicinsk utvecklingsbiologi.
    Heterogeneity in retinoblastoma: a tale of molecules and models2017Inngår i: CLINICAL AND TRANSLATIONAL MEDICINE, ISSN 2001-1326, Vol. 6, artikkel-id 42Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Retinoblastoma, an intraocular pediatric cancer, develops in the embryonic retina following biallelic loss of RB1. However, there is a wide range of genetic and epigenetic changes that can affect RB1 resulting in different clinical outcomes. In addition, other transformations, such as MYCN amplification, generate particularly aggressive tumors, which may or may not be RB1 independent. Recognizing the cellular characteristics required for tumor development, by identifying the elusive cell-of-origin for retinoblastoma, would help us understand the development of these tumors. In this review we summarize the heterogeneity reported in retinoblastoma on a molecular, cellular and tissue level. We also discuss the challenging heterogeneity in current retinoblastoma models and suggest future platforms that could contribute to improved understanding of tumor initiation, progression and metastasis in retinoblastoma, which may ultimately lead to more patient-specific treatments.

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