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  • 1.
    De Pieri, Andrea
    et al.
    Natl Univ Galway Ireland NUI Galway, Regenerat Modular & Dev Engn Lab REMODEL, Galway, Ireland;Natl Univ Galway Ireland NUI Galway, Ctr Res Med Devices CURAM, SFI, Galway, Ireland;Proxy Biomed Ltd, Galway, Ireland.
    Ribeiro, Sofia
    Natl Univ Galway Ireland NUI Galway, Regenerat Modular & Dev Engn Lab REMODEL, Galway, Ireland;Natl Univ Galway Ireland NUI Galway, Ctr Res Med Devices CURAM, SFI, Galway, Ireland;Medtron Sofradim Prod, Trevoux, France.
    Tsiapalis, Dimitrios
    Natl Univ Galway Ireland NUI Galway, Regenerat Modular & Dev Engn Lab REMODEL, Galway, Ireland;Natl Univ Galway Ireland NUI Galway, Ctr Res Med Devices CURAM, SFI, Galway, Ireland.
    Eglin, David
    AO Res Inst Davos, Clavadelerstr 8, CH-7270 Davos, Switzerland.
    Bohner, Marc
    RMS Fdn, POB 203,Bischmattstr 12, CH-2544 Bettlach, Switzerland.
    Dubruel, Peter
    Univ Ghent, Polymer Chem & Biomat Res Grp, Krijgslaan 281 S4 Bis, B-9000 Ghent, Belgium.
    Procter, Philip
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. CPP SARL Divonne Les Bains, F-01220 Divonne Les Bains, France.
    Zeugolis, Dimitrios I.
    Natl Univ Galway Ireland NUI Galway, Regenerat Modular & Dev Engn Lab REMODEL, Galway, Ireland;Natl Univ Galway Ireland NUI Galway, Ctr Res Med Devices CURAM, SFI, Galway, Ireland.
    Bayon, Yves
    Medtron Sofradim Prod, Trevoux, France.
    Joint academic and industrial efforts towards innovative and efficient solutions for clinical needs2018In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 29, no 8, article id 129Article, review/survey (Refereed)
    Abstract [en]

    The 4(th) Translational Research Symposium (TRS) was organised at the annual meeting of the European Society for Biomaterials (ESB) 2017, Athens, Greece, with a focus on 'Academia-Industry Clusters of Research for Innovation Catalysis'. Collaborations between research institutes and industry can be sustained in several ways such as: European Union (EU) funded consortiums; syndicates of academic institutes, clinicians and industries; funding from national governments; and private collaborations between universities and companies. Invited speakers from industry and research institutions presented examples of these collaborations in the translation of research ideas or concepts into marketable products. The aim of the present article is to summarize the key messages conveyed during these lectures. In particular, emphasis is put on the challenges to appropriately identify and select unmet clinical needs and their translation by ultimately implementing innovative and efficient solutions achieved through joint academic and industrial efforts.

  • 2.
    Janson, Oscar
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Sörensen, Jan Henrik
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Procter, Philip
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Welch, Ken
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Development of a novel multifunctional hydroxyapatite coating for orthopedic implantsManuscript (preprint) (Other academic)
  • 3.
    Janson, Oscar
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Sörensen, Jan Henrik
    Doctores Sorensen OHG, Segeberger Landstr, Kiel, Germany.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Procter, Philip
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Welch, Ken
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Evaluation of an alkali-treated and hydroxyapatite-coated orthopedic implant loaded with tobramycin2019In: Journal of biomaterials applications, ISSN 0885-3282, E-ISSN 1530-8022, Vol. 34, no 5, p. 699-720, article id UNSP 0885328219867968Article in journal (Refereed)
    Abstract [en]

    An approximately 1-µm thick hydroxyapatite coating was biomimetically deposited on an alkali-treated, commercially available orthopedic screw surface (type II anodized titanium). Tobramycin loaded into the coating via a simple soaking method was shown to provide a sustained release above the minimal inhibitory concentration 0.2 µg/µl for up to two days. Agar diffusion tests showed that the tobramycin-loaded coating was able to produce a zone of inhibition against Staphylococcus aureus for up to five days. Biocompatibility testing using outgrowth endothelial cells and primary osteoblasts suggested that good cell compatibility of the coating can be expected in vivo. A rabbit distal femur condyle model was used for in vivo evaluation of the antibacterial efficacy of the tobramycin-loaded coating, and this pilot study showed that the release of tobramycin was sufficient to locally eliminate very large amounts of bacteria in vivo (inoculation dose 104–105 CFU S. aureus/test site).

  • 4.
    Joffre, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Isaksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics.
    Procter, Philip
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Trabecular deformations during screw pull-out: a micro-CT study of lapine bone2017In: Biomechanics and Modeling in Mechanobiology, ISSN 1617-7959, E-ISSN 1617-7940, Vol. 16, no 4, p. 1349-1359Article in journal (Refereed)
    Abstract [en]

    The mechanical fixation of endosseous implants, such as screws, in trabecular bone is challenging because of the complex porous microstructure. Development of new screw designs to improve fracture fixation, especially in high-porosity osteoporotic bone, requires a profound understanding of how the structural system implant/trabeculae interacts when it is subjected to mechanical load. In this study, pull-out tests of screw implants were performed. Screws were first inserted into the trabecular bone of rabbit femurs and then pulled out from the bone inside a computational tomography scanner. The tests were interrupted at certain load steps to acquire 3D images. The images were then analysed with a digital volume correlation technique to estimate deformation and strain fields inside the bone during the tests. The results indicate that the highest shear strains are concentrated between the inner and outer thread diameter, whereas compressive strains are found at larger distances from the screw. Tensile strains were somewhat smaller. Strain concentrations and the location of trabecular failures provide experimental information that could be used in the development of new screw designs and/or to validate numerical simulations.

  • 5.
    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 University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    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 augmentation2017In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 11, no 7, p. 1974-1985Article in journal (Refereed)
    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.

  • 6. Kettenberger, Ulrike
    et al.
    Ston, Julien
    Thein, Eric
    Procter, Philip
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Pioletti, Dominique P.
    Does locally delivered Zoledronate influence pen-implant bone formation?: Spatio-temporal monitoring of bone remodeling in vivo2014In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, no 37, p. 9995-10006Article in journal (Refereed)
    Abstract [en]

    Bisphosphonates are known for their strong inhibitory effect on bone resorption. Their influence on bone formation however is less clear. In this study we investigated the spatio-temporal effect of locally delivered Zoledronate on pen-implant bone formation and resorption in an ovariectomized rat femoral model. A cross-linked hyaluronic acid hydrogel was loaded with the drug and applied bilaterally in predrilled holes before inserting polymer screws. Static and dynamic bone parameters were analyzed based on in vivo microCT scans performed first weekly and then biweekly. The results showed that the locally released Zoledronate boosted bone formation rate up to 100% during the first 17 days after implantation and reduced the bone resorption rate up to 1000% later on. This shift in bone remodeling resulted in an increase in bone volume fraction (BV/TV) by 300% close to the screw and 100% further away. The double effect on bone formation and resorption indicates a great potential of Zoledronateloaded hydrogel for enhancement of pen-implant bone volume which is directly linked to improved implant fixation.

  • 7.
    Liu, Xiuwen
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Pujari-Palmer, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Wenner, David
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Procter, Philip
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Insley, Gerard
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. GPBio Ltd, Unit 4D, Western Business Pk, Shannon V14 RW92, Clare, Ireland.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. Uppsala Univ, Dept Engn, Appl Mat Sci, S-75121 Uppsala, Sweden.
    Adhesive Cements That Bond Soft Tissue Ex Vivo2019In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 12, no 15, article id 2473Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to evaluate the soft tissue bond strength of a newly developed, monomeric, biomimetic, tissue adhesive called phosphoserine modified cement (PMC). Two types of PMCs were evaluated using lap shear strength (LSS) testing, on porcine skin: a calcium metasilicate (CS1), and alpha tricalcium phosphate (alpha TCP) PMC. CS1 PCM bonded strongly to skin, reaching a peak LSS of 84, 132, and 154 KPa after curing for 0.5, 1.5, and 4 h, respectively. Cyanoacrylate and fibrin glues reached an LSS of 207 kPa and 33 kPa, respectively. alpha TCP PMCs reached a final LSS of approximate to 110 kPa. In soft tissues, stronger bond strengths were obtained with alpha TCP PMCs containing large amounts of amino acid (70-90 mol%), in contrast to prior studies in calcified tissues (30-50 mol%). When alpha TCP particle size was reduced by wet milling, and for CS1 PMCs, the strongest bonding was obtained with mole ratios of 30-50% phosphoserine. While PM-CPCs behave like stiff ceramics after setting, they bond to soft tissues, and warrant further investigation as tissue adhesives, particularly at the interface between hard and soft tissues.

  • 8.
    Munoz, Jorge Solana
    et al.
    Ecole Polytech Fed Lausanne, Inst Bioengn, Lab Biomech Orthoped, Lausanne, Switzerland.
    Kettenberger, Ulrike
    Ecole Polytech Fed Lausanne, Inst Bioengn, Lab Biomech Orthoped, Lausanne, Switzerland.
    Procter, Philip
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Pioletti, Dominique P.
    Ecole Polytech Fed Lausanne, Inst Bioengn, Lab Biomech Orthoped, Lausanne, Switzerland.
    Non-setting, injectable biomaterials containing particulate hydroxyapatite can increase primary stability of bone screws in cancellous bone2018In: Clinical Biomechanics, ISSN 0268-0033, E-ISSN 1879-1271, Vol. 59, p. 174-180Article in journal (Refereed)
    Abstract [en]

    Background: Fracture fixation in weak bone is still a clinical challenge. Screw augmentation was shown to successfully increase their primary stability. The currently used calcium phosphate or polymeric bone cements, however, present important drawbacks such as induced toxicity and/or impaired bone neo-formation. A new approach to enhance bone screw primary stability without affecting bone formation is the use of non-setting, calcitim phosphate loaded soft materials as the augmentation material. Methods: Two types of biomaterials (non-crosslinked hyaluronic acid as viscous fluid and agar as hydrogel) were loaded with 40 wt/vol% of hydroxyapatite particles and characterized. The screw augmentation effect of all materials was evaluated through pull-out tests in bovine cancellous bone and compared to the non-augmented situation (control). The bone mineral density of each test sample was measured with CT scans and was used to normalize the pull-out strength. Findings: Both materials loaded with hydroxyapatite increased the normalized pull-out strength of the screws compared to control samples and particle-free materials. This counter-intuitive augmentation effect increased with decreasing bone mineral density and was independent from the type of the soft materials used. Interpretation: We were able to demonstrate that non-setting, injectable biomaterials loaded with ceramic particles can significantly enhance the primary stability of bone screws. This material combination opens the unique possibility to achieve a screw augmentation effect without impairing or even potentially favoring the bone formation in proximity to the screw. This effect would be particularly advantageous for the treatment of osteoporotic bone fractures requiring a stabilization with bone screws.

  • 9.
    Procter, Philip
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Pujari-Palmer, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. Uppsala University.
    Hulsart Billström, Gry
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Insley, Gerard
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    A new ex-vivo murine model for evaluation of adhesiveness of a novel biomimetic bone glue2018Conference paper (Refereed)
  • 10.
    Pujari-Palmer, Michael
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. 0000-0001-7004-2853.
    Guo, Hua
    Stockholm Univ, Dept Mat & Environm Chem, Stockholm, Sweden.
    Wenner, David
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Autefage, Hélène
    Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden.
    Spicer, Christopher D.
    Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden.
    Stevens, Molly M.
    Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden; Imperial Coll London, Dept Bioengn, Dept Mat, London, England; Imperial Coll London, Inst Biomed Engn, London, England.
    Omar, Omar
    Univ Gothenburg, Inst Clin Sci, Dept Biomat, Gothenburg, Sweden.
    Thomsen, Peter
    Univ Gothenburg, Inst Clin Sci, Dept Biomat, Gothenburg, Sweden.
    Edén, Mattias
    Stockholm Univ, Dept Mat & Environm Chem, Stockholm, Sweden.
    Insley, Gerard
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Procter, Philip
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    A Novel Class of Injectable Bioceramics that Glue Tissues and Biomaterials2018In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 11, no 12, article id 2492Article in journal (Refereed)
    Abstract [en]

    Calcium phosphate cements (CPCs) are clinically effective void fillers that are capable of bridging calcified tissue defects and facilitating regeneration. However, CPCs are completely synthetic/inorganic, unlike the calcium phosphate that is found in calcified tissues, and they lack an architectural organization, controlled assembly mechanisms, and have moderate biomechanical strength, which limits their clinical effectiveness. Herein, we describe a new class of bioinspired CPCs that can glue tissues together and bond tissues to metallic and polymeric biomaterials. Surprisingly, alpha tricalcium phosphate cements that are modified with simple phosphorylated amino acid monomers of phosphoserine (PM-CPCs) bond tissues up to 40-fold stronger (2.5–4 MPa) than commercial cyanoacrylates (0.1 MPa), and 100-fold stronger than surgical fibrin glue (0.04 MPa), when cured in wet-field conditions. In addition to adhesion, phosphoserine creates other novel properties in bioceramics, including a nanoscale organic/inorganic composite microstructure, and templating of nanoscale amorphous calcium phosphate nucleation. PM-CPCs are made of the biocompatible precursors calcium, phosphate, and amino acid, and these represent the first amorphous nano-ceramic composites that are stable in liquids.

  • 11.
    Pujari-Palmer, Michael
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Robo, Céline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Procter, Philip
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Influence of cement compressive strength and porosity on augmentation performance in a model of orthopedic screw pull-out2018In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 77, p. 624-633Article in journal (Refereed)
    Abstract [en]

    Disease and injuries that affect the skeletal system may require surgical intervention and internal fixation, i.e. orthopedic plate and screw insertion, to stabilize the injury and facilitate tissue repair. If the surrounding bone quality is poor the screws may migrate, or the bone may fail, resulting in screw pull-out. Though numerous studies have shown that cement augmentation of the interface between bone and implant can increase screw holding strength in bone, the physical properties of cement that influence pull-out force have not been investigated. The present study sought to determine how the physical properties of calcium phosphate cements (CPCs), and the strength of the biological or synthetic material surrounding the augmented screw, affected the corresponding orthopedic screw pull-out force in urethane foam models of healthy and osteoporotic bone (Sawbones). In the simplest model, where only the bond strength between screw thread and cement (without Sawbone) was tested, the correlation between pull-out force and cement compressive strength (R2 = 0.79) was weaker than correlation with total cement porosity (R2 = 0.89). In open pore Sawbone that mimics “healthy” cancellous bone density the stronger cements produced higher pull-out force (50-60% increase). Higher strength, lower porosity, cements also produced higher pull-out forces (50-190% increase) in Sawbones with cortical fixation if the failure strength of the cortical material was similar to (bovine tibial bone), or greater than (metal shell), actual cortical bone. This result is of particular clinical relevance where fixation with a metal plate implant is indicated, as the nearby metal can simulate a thicker cortical shell and, thereby, increase the pull-out force of screws augmented with stronger cements. The improvement in pull-out force was apparent even at low augmentation volumes of 0.5 ml (50% increase), which suggest that in clinical situations where augmentation volume is limited the stronger, lower porosity CPCs may still produce a significant improvement in screw holding strength. When correlations of all the tested models were compared both cement porosity and compressive strength accurately predicted pull-out force (R2=1.00, R2=0.808), though prediction accuracy depended upon the strength of the material surrounding the Sawbone. The correlations strength was low for bone with no, or weak, cortical fixation. Higher strength and lower porosity CPCs also produced greater pull-out force (1-1.5 kN) than commercial CPC (0.2-0.5kN), but lower pull-out force than PMMA (2-3 kN). The results of this study suggest that the likelihood of screw fixation failure may be reduced by selecting calcium phosphate cements with lower porosity and higher bulk strength, in patients with healthy bone mineral density and/or sufficient cortical thickness. This is of particular clinical relevance when fixation with metal plates is indicated, or where the augmentation volume is limited.

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