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  • 1. 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 model2014Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, s. 65-65Artikkel i tidsskrift (Annet vitenskapelig)
  • 2.
    Diez-Escudero, Anna
    et al.
    UPC, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 16, Barcelona 08019, Spain;UPC, Barcelona Res Ctr Multiscale Sci & Engn, Barcelona, Spain.
    Torreggiani, Elena
    IRCCS Ist Ortoped Rizzoli, Orthopaed Pathophysiol & Regenerat Med Unit, Bologna, Italy.
    Di Pompo, Gemma
    IRCCS Ist Ortoped Rizzoli, Orthopaed Pathophysiol & Regenerat Med Unit, Bologna, Italy.
    Espanol, Montserrat
    UPC, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 16, Barcelona 08019, Spain;UPC, Barcelona Res Ctr Multiscale Sci & Engn, Barcelona, Spain.
    Persson, Cecilia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Ciapetti, Gabriela
    IRCCS Ist Ortoped Rizzoli, Orthopaed Pathophysiol & Regenerat Med Unit, Bologna, Italy.
    Baldini, Nicola
    IRCCS Ist Ortoped Rizzoli, Orthopaed Pathophysiol & Regenerat Med Unit, Bologna, Italy;Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy.
    Ginebra, Maria-Pau
    UPC, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 16, Barcelona 08019, Spain;UPC, Barcelona Res Ctr Multiscale Sci & Engn, Barcelona, Spain;Barcelona Inst Sci & Technol, Inst Bioengn Catalonia, Barcelona, Spain.
    Effect of calcium phosphate heparinization on the in vitro inflammatory response and osteoclastogenesis of human blood precursor cells2019Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 13, nr 7, s. 1217-1229Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The immobilization of natural molecules on synthetic bone grafts stands as a strategy to enhance their biological interactions. During the early stages of healing, immune cells and osteoclasts (OC) modulate the inflammatory response and resorb the biomaterial, respectively. In this study, heparin, a naturally occurring molecule in the bone extracellular matrix, was covalently immobilized on biomimetic calcium-deficient hydroxyapatite (CDHA). The effect of heparin-functionalized CDHA on inflammation and osteoclastogenesis was investigated using primary human cells and compared with pristine CDHA and beta-tricalcium phosphate (beta-TCP). Biomimetic substrates led to lower oxidative stresses by neutrophils and monocytes than sintered beta-TCP, even though no further reduction was induced by the presence of heparin. In contrast, heparinized CDHA fostered osteoclastogenesis. Optical images of stained TRAP positive cells showed an earlier and higher presence of multinucleated cells, compatible with OC at 14 days, while pristine CDHA and beta-TCP present OC at 21-28 days. Although no statistically significant differences were found in the OC activity, microscopy images evidenced early stages of degradation on heparinized CDHA, compatible with osteoclastic resorption. Overall, the results suggest that the functionalization with heparin fostered the formation and activity of OC, thus offering a promising strategy to integrate biomaterials in the bone remodelling cycle by increasing their OC-mediated resorption.

  • 3.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Evaluation of biomaterials derived from ecm components2014Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, s. 12-12Artikkel i tidsskrift (Annet vitenskapelig)
  • 4.
    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-linking2014Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, s. 150-150Artikkel i tidsskrift (Annet vitenskapelig)
  • 5.
    Hulsart-Billstrom, Gry
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Estrada, Sergio
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET.
    Lubberink, Mark
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för nuklearmedicin och PET.
    Antoni, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Plattformen för preklinisk PET. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    BMP-2 Induced bone regeneration visualized by PET and SPECT2014Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, s. 513-513Artikkel i tidsskrift (Annet vitenskapelig)
  • 6.
    Hulsart-Billstrom, Gry
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Nouhi, Shirin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialfysik.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Öhman, Caroline
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Iodine-enhanced contrast applicable for microcomputed tomography2014Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, s. 245-246Artikkel i tidsskrift (Fagfellevurdert)
  • 7.
    Hulsart-Billström, Gry
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Bergman, Kristoffer
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Andersson, Brittmarie
    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.
    Larsson, Sune
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    Jonsson, Kenneth B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Ortopedi.
    A uni-cortical femoral defect model in the rat: evaluation using injectable hyaluronan hydrogel as a carrier for bone morphogenetic protein-22015Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 9, nr 7, s. 799-807Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The development of biomaterial for bone regeneration requires animal models that are reliable and designed to mimic clinically relevant situations. We have previously investigated hydrogels comprised of modified hyaluronic acid and polyvinyl alcohol in models of ectopic bone formation. This hydrogel induces bone regeneration when loaded with bone morphogenetic proteins (BMPs). To allow further optimization of hydrogels, we developed a new, femoral, non-critical-sized cortical defect model. In the rat femur, we drilled standardized, elongated unilateral cortical defects that did not require stabilization and that could be created bilaterally to allow paired comparisons of biomaterials. After optimizing the defect size, subsequent stress fractures occurred in only 8% and the defect healed partially over the 40 day study period. In a time-course experiment, we treated bone defects with the previously studied hyaluronan hydrogel loaded with 10 µg hydroxyapatite and 6 µg BMP-2. The shape of the defect allowed controlled containment of the material within the defect. The defect in the right leg was left untreated, while the left defect was filled with 40 µl of the BMP hydrogel. As determined by pQCT analysis, the treated defects had a higher bone mineral content, bone area and bone density than control defects. The relative difference was greatest between the groups at 10 and 20 days and diminished as the defect healed in the untreated legs. We conclude that this animal model allows facile and rapid screening of biomaterials for bone regeneration in cortical femoral defects without requiring external fixation.

  • 8.
    Kettenberger, Ulrike
    et al.
    Ecole Polytech Fed Lausanne, Inst Bioengn, Lab Biomech Orthopaed, Stn 19, CH-1015 Lausanne, Switzerland..
    Luginbuehl, Vera
    Zurich Univ Appl Sci, Inst Biotechnol, Pharmaceut Technol, Winterthur, Switzerland..
    Procter, Philip
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Pioletti, Dominique P.
    Ecole Polytech Fed Lausanne, Inst Bioengn, Lab Biomech Orthopaed, Stn 19, CH-1015 Lausanne, Switzerland..
    In vitro and in vivo investigation of bisphosphonate-loaded hydroxyapatite particles for peri-implant bone augmentation2017Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 11, nr 7, s. 1974-1985Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Locally applied bisphosphonates, such as zoledronate, have been shown in several studies to inhibit peri-implant bone resorption and recently to enhance peri-implant bone formation. Studies have also demonstrated positive effects of hydroxyapatite (HA) particles on peri-implant bone regeneration and an enhancement of the anti-resorptive effect of bisphosphonates in the presence of calcium. In the present study, both hydroxyapatite nanoparticles (nHA) and zoledronate were combined to achieve a strong reinforcing effect on peri-implant bone. The nHA-zoledronate combination was first investigated in vitro with a pre-osteoclastic cell assay (RAW 264.7) and then in vivo in a rat model of postmenopausal osteoporosis. The in vitro study confirmed that the inhibitory effect of zoledronate on murine osteoclast precursor cells was enhanced by loading the drug on nHA. For the in vivo investigation, either zoledronate-loaded or pure nHA were integrated in hyaluronic acid hydrogel. The gels were injected in screw holes that had been predrilled in rat femoral condyles before the insertion of miniature screws. Micro-CT-based dynamic histomorphometry and histology revealed an unexpected rapid mineralization of the hydrogel in vivo through formation of granules, which served as scaffold for new bone formation. The delivery of zoledronate-loaded nHA further inhibited a degradation of the mineralized hydrogel as well as a resorption of the peri-implant bone as effectively as unbound zoledronate. Hyaluronic acid with zoledronate-loaded nHA, thanks to its dual effect on inducing a rapid mineralization and preventing resorption, is a promising versatile material for bone repair and augmentation.

  • 9.
    Kootala, Sujit
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Ossipov, Dmitri
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Zhang, Yu
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Hyaluronic acid linked bisphosphonates as a step towards targeted therapy for osteoporosis2014Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, s. 420-421Artikkel i tidsskrift (Annet vitenskapelig)
  • 10.
    König, Niclas
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neuroanatomi.
    Trolle, Carl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neuroanatomi.
    Kapuralin, Katarina
    University of Zagreb School of Medicine.
    Adameyko, Igor
    Karolinska Institutet.
    Mitrecic, Dinko
    University of Zagreb School of Medicine.
    Aldskogius, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neuroanatomi.
    Shortland, Peter
    Queen Mary University of London.
    Kozlova, Elena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neuroanatomi.
    Murine neural crest stem cells and embryonic stem cell derived neuron precursors survive and differentiate after transplantation in a model of dorsal root avulsion2017Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 11, nr 1, s. 129-137Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Spinal root avulsion results in paralysis and sensory loss, and is commonly associated with chronic pain. In addition to the failure of avulsed dorsal root axons to regenerate into the spinal cord, avulsion injury leads to extensive neuroinflammation and degeneration of second order neurons in the dorsal horn. The ultimate objective with the treatment of this condition is to counteract degeneration of spinal cord neurons and to achieve functionally useful regeneration/reconnection of sensory neurons with spinal cord neurons. Here we explore if stem cells transplanted on the surface of avulsed spinal cord can survive, differentiate and migrate into the damaged spinal cord during the first few weeks after this intervention. Murine boundary cap neural crest stem cells (bNCSCs) or embryonic stem cell (ESC)-derived, pre-differentiated neuron precursors were implanted acutely at the junction between avulsed dorsal roots L3-L6 and the spinal cord. Both types of cells survived transplantation, but showed distinctly different modes of differentiation. Thus, bNCSCs migrated into the spinal cord, expressed glial markers, and formed elongated tubes in the peripheral nervous system (PNS) compartment of the avulsed dorsal root transitional zone(DRTZ) area. In contrast, the ESC-transplants remained at the site of implantation and differentiated to motor neurons and interneurons. These data show that both stem cell types successfully survive implantation to the acutely injured spinal cord and maintained their differentiation and migration potential. These data suggest that depending on the source of neural stem cells, they can play different beneficial roles for recovery after dorsal root avulsion.

  • 11.
    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.

  • 12.
    Sladkova, Martina
    et al.
    The New York Stem Cell Foundation Research Institute.
    Pujari-Palmer, Michael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Öhman, Caroline
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    Cheng, Jiayi
    The New York Stem Cell Foundation Research Institute.
    Al-Ansari, Shoug
    The New York Stem Cell Foundation Research Institute.
    Saad, Munerah
    The New York Stem Cell Foundation Research Institute.
    Engqvist, Håkan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Tillämpad materialvetenskap.
    de Peppo, Giuseppe Maria
    The New York Stem Cell Foundation Research Institute.
    Engineering human bone grafts with new macroporous calcium phosphate cement scaffolds2018Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 12, nr 3, s. 715-726Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Bone engineering opens the possibility to grow large amounts of tissue products by combining patient-specific cells with compliant biomaterials. Decellularized tissue matrices represent suitable biomaterials, but availability, long processing time, excessive cost, and concerns on pathogen transmission have led to the development of biomimetic synthetic alternatives. We recently fabricated calcium phosphate cement (CPC) scaffolds with variable macroporosity using a facile synthesis method with minimal manufacturing steps and demonstrated long-term biocompatibility in vitro. However, there is no knowledge on the potential use of these scaffolds for bone engineering and whether the porosity of the scaffolds affects osteogenic differentiation and tissue formation in vitro. In this study, we explored the bone engineering potential of CPC scaffolds with two different macroporosities using human mesenchymal progenitors derived from induced pluripotent stem cells (iPSC-MP) or isolated from bone marrow (BMSC). Biomimetic decellularized bone scaffolds were used as reference material in all experiments. The results demonstrate that, irrespective of their macroporosity, the CPC scaffolds tested in this study support attachment, viability, and growth of iPSC-MP and BMSC cells similarly to decellularized bone. Importantly, the tested materials sustained differentiation of the cells as evidenced by increased expression of osteogenic markers and formation of a mineralized tissue. In conclusion, the results of this study suggest that the CPC scaffolds fabricated using our method are suitable to engineer bone grafts from different cell sources and could lead to the development of safe and more affordable tissue grafts for reconstructive dentistry and orthopaedics and in vitro models for basic and applied research.

  • 13. Zeiai, S.
    et al.
    Zhao, J.
    Ekblad, A.
    Nordenskjold, A.
    Hilborn, Jöns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Polymerkemi.
    Gotherstrom, C.
    Fossum, M.
    From bone marrow to an autologous urothelium-PCL-collagen transplant2014Inngår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, s. 294-295Artikkel i tidsskrift (Annet vitenskapelig)
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