uu.seUppsala University Publications
Change search
Refine search result
1 - 30 of 30
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Asif, Sana
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ekdahl, Kristina N
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Linnæus Center of Biomaterials Chemistry, Linnæus University, SE-391 82 Kalmar, Sweden.
    Fromell, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Gustafson, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Paediatric Surgery.
    Barbu, Andreea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Le Bland, Katarina
    Division of Clinical Immunology and Transfusion Medicine, Department of Laboratory Medicine, Karolinska Institute, and Hematology and Regenerat ive Medicine Centre at Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Teramura, Yuji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Department of Bioengineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
    Heparinization of cell surfaces with short pepetide-conjugated PEG-lipid regulates thromboinflammation in thransplantation of human MSCs and hepatocytes2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 35, p. 194-205Article in journal (Refereed)
    Abstract [en]

    Infusion of therapeutic cells into humans is associated with immune responses, including thromboinflammation, which result in a large loss of transplanted cells\ To address these problems, heparinization of the cell surfaces was achieved by a cell-surface modification technique using polyethylene glycol conjugated phospholipid (PEG-lipid) derivatives. A short heparin-binding peptide was conjugated to the PEG-lipid for immobilization of heparin conjugates on the surface of human mesenchymal stem cells (hMSCs) and human hepatocytes. Here three kinds of heparin-binding peptides were used for immobilizing heparin conjugates and examined for the antithrombogenic effects on the cell surface. The heparinized cells were incubated in human whole blood to evaluate their hemocompatibility by measuring blood parameters such as platelet count, coagulation markers, complement markers, and Factor Xa activity. We found that one of the heparin-binding peptides did not show cytotoxicity after the immobilization with heparin conjugates. The degree of binding of the heparin conjugates on the cell surface (analyzed by flow cytometer) depended on the ratio of the active peptide to control peptide. For both human MSCs and hepatocytes in whole-blood experiments, no platelet aggregation was seen in the heparin conjugate-immobilized cell group vs. the controls (non-coated cells or control peptide). Also, the levels of thrombin-antithrombin complex (TAT), C3a, and sC5b-9 were significantly lower than those of the controls, indicating a lower activation of coagulation and complement. Factor Xa analysis indicated that the heparin conjugate was still active on the cell surface at 24 h post-coating. It is possible to immobilize heparin conjugates onto hMSC and human hepatocyte surfaces and thereby protect the cell surfaces from damaging thromboinflammation. Statement of Signigficance We present a promising approach to enhance the biocompatibility of therapeutic cells. Here we used short peptide-conjugated PEG-lipid for cell surface modification and heparin conjugates for the coating of human hepatocytes and MSCs. We screened the short peptides to find higher affinity for heparinization of cell surface and performed hemocompatibility assay of heparinized human hepatocytes and human MSCs in human whole blood. Using heparin-binding peptide with higher affinity, not only coagulation activation but also complement activation was significantly suppressed. Thus, it was possible to protect human hepatocytes and human MSCs from the attack of thromboinflammatory activation, which can contribute to the improvement graft survival.

  • 2.
    Barba, Albert
    et al.
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Maazouz, Yassine
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Diez-Escudero, Anna
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Rappe, Katrin
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autònoma de Barcelona.
    Espanol, Montserrat
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Montufar, Edgar
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Öhman, Caroline
    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.
    Fontecha, Pedro
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autònoma de Barcelona.
    Manzanares, Maria-Cristina
    Human Anatomy and Embryology Unit, Department of Pathology and Experimental Therapeutics, Universitat de Barcelona.
    Franch, Jordi
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autònoma de Barcelona.
    Ginebra, Maria-Pau
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Osteogenesis by foamed and 3D-printed nanostructured calcium phosphate scaffolds: Effect of pore architecture2018In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 79, p. 135-147Article in journal (Refereed)
    Abstract [en]

    There is an urgent need of synthetic bone grafts with enhanced osteogenic capacity. This can be achieved by combining biomaterials with exogenous growth factors, which however can have numerous undesired side effects, but also by tuning the intrinsic biomaterial properties. In a previous study, we showed the synergistic effect of nanostructure and pore architecture of biomimetic calcium deficient hydroxyapatite (CDHA) scaffolds in enhancing osteoinduction, i.e. fostering the differentiation of mesenchymal stem cells to bone forming cells. This was demonstrated by assessing bone formation after implanting the scaffolds intramuscularly. The present study goes one step forward, since it analyzes the effect of the geometrical features of the same CDHA scaffolds, obtained either by 3D-printing or by foaming, on the osteogenic potential and resorption behaviour in a bony environment. After 6 and 12 weeks of intraosseous implantation, both bone formation and material degradation had been drastically affected by the macropore architecture of the scaffolds. Whereas nanostructured CDHA was shown to be highly osteoconductive both in the robocast and foamed scaffolds, a superior osteogenic capacity was observed in the foamed scaffolds, which was associated with their higher intrinsic osteoinductive potential. Moreover, they showed a significantly higher cell-mediated degradation than the robocast constructs, with a simultaneous and progressive replacement of the scaffold by new bone. In conclusion, these results demonstrate that the control of macropore architecture is a crucial parameter in the design of synthetic bone grafts, which allows fostering both material degradation and new bone formation. Statement of Significance 3D-printing technologies open new perspectives for the design of patient-specific bone grafts, since they allow customizing the external shape together with the internal architecture of implants. In this respect, it is important to design the appropriate pore geometry to maximize the bone healing capacity of these implants. The present study analyses the effect of pore architecture of nanostructured hydroxyapatite scaffolds, obtained either by 3D-printing or foaming, on the osteogenic potential and scaffold resorption in an in vivo model. While nanostructured hydroxyapatite showed excellent osteoconductive properties irrespective of pore geometry, we demonstrated that the spherical, concave macropores of foamed scaffolds significantly promoted both material resorption and bone regeneration compared to the 3D-printed scaffolds with orthogonal-patterned struts and therefore prismatic, convex macropores.

  • 3.
    Cai, Yixiao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Edin, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Alexsson, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Gudjonsson, Olafur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Karlsson, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Strategy towards independent electrical stimulation from cochlear implants: Guided auditory neuron growth on topographically modified nanocrystalline diamond2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 31, p. 211-220Article in journal (Refereed)
    Abstract [en]

    Cochlear implants (CI) have been used for several decades to treat patients with profound hearing loss. Nevertheless, results vary between individuals, and fine hearing is generally poor due to the lack of discrete neural stimulation from the individual receptor hair cells. A major problem is the deliverance of independent stimulation signals to individual auditory neurons. Fine hearing requires significantly more stimulation contacts with intimate neuron/electrode interphases from ordered axonal re-growth, something current CI technology cannot provide.

    Here, we demonstrate the potential application of micro-textured nanocrystalline diamond (NCD) surfaces on CI electrode arrays. Such textured NCD surfaces consist of micrometer-sized nail-head-shaped pillars (size 5 5 lm2) made with sequences of micro/nano-fabrication processes, including sputtering, photolithography and plasma etching.

    The results show that human and murine inner-ear ganglion neurites and, potentially, neural progenitor cells can attach to patterned NCD surfaces without an extracellular matrix coating. Microscopic methods revealed adhesion and neural growth, specifically along the nail-head-shaped NCD pillars in an ordered manner, rather than in non-textured areas. This pattern was established when the inter-NCD pillar distance varied between 4 and 9 lm.

    The findings demonstrate that regenerating auditory neurons show a strong affinity to the NCD pillars, and the technique could be used for neural guidance and the creation of new neural networks. Together with the NCD’s unique anti-bacterial and electrical properties, patterned NCD surfaces could provide designed neural/electrode interfaces to create independent electrical stimulation signals in CI electrode arrays for the neural population.

  • 4.
    Canal, Cristina
    et al.
    Technical University of Catalonia.
    Pastorino, David
    Technical University of Catalonia.
    Mestres, Gemma
    Technical University of Catalonia.
    Schuler, Philipp
    Ginebra, Maria-Pau
    Technical University of Catalonia.
    Relevance of microstructure for the early antibiotic release of fresh and pre-set calcium phosphate cements2013In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 9, no 9, p. 8403-8412Article in journal (Refereed)
    Abstract [en]

    Calcium phosphate cements (CPCs) have great potential as carriers for controlled release and vectoring of drugs in the skeletal system. However, a lot of work still has to be done in order to obtain reproducible and predictable release kinetics. A particular aspect that adds complexity to these materials is that they cannot be considered as stable matrices, since their microstructure evolves during the setting reaction.The aims of the present work were to analyze the effect of the microstructural evolution of the CPC during the setting reaction on the release kinetics of the antibiotic doxycycline hyclate and to assess the effect of the antibiotic on the microstructural development of the CPC. The incorporation of the drug in the CPC modified the textural and microstructural properties of the cements by acting as a nucleating agent for the heterogeneous precipitation of hydroxyapatite crystals, but did not affect its antibacterial activity. In vitro release experiments were carried out on readily prepared cements (fresh CPCs), and compared to those of pre-set CPCs. No burst release was found in any formulation. A marked difference in release kinetics was found at the initial stages; the evolving microstructure of fresh CPCs led to a two-step release. Initially, when the carrier was merely a suspension of a-TCP particles in water, a faster release was recorded, which rapidly evolved to a zero-order release. In contrast, pre-set CPCs released doxycycline following non-Fickian diffusion. The final release percentage was related to the total porosity and entrance pore size of each biomaterial.

  • 5.
    Elgali, Ibrahim
    et al.
    BIOMATCELL VINN Excellence Ctr Biomat & Cell Ther, Gothenburg, Sweden.;Univ Gothenburg, Dept Biomat, Inst Clin Sci, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden..
    Turri, Alberto
    BIOMATCELL VINN Excellence Ctr Biomat & Cell Ther, Gothenburg, Sweden.;Univ Gothenburg, Dept Biomat, Inst Clin Sci, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden.;Publ Dent Hlth Care, Inst Odontol, Branemark Clin, Gothenburg, Sweden..
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Norlindh, Birgitta
    BIOMATCELL VINN Excellence Ctr Biomat & Cell Ther, Gothenburg, Sweden.;Univ Gothenburg, Dept Biomat, Inst Clin Sci, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden..
    Johansson, Anna
    BIOMATCELL VINN Excellence Ctr Biomat & Cell Ther, Gothenburg, Sweden.;Univ Gothenburg, Dept Biomat, Inst Clin Sci, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden..
    Dahlin, Christer
    BIOMATCELL VINN Excellence Ctr Biomat & Cell Ther, Gothenburg, Sweden.;Univ Gothenburg, Dept Biomat, Inst Clin Sci, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden.;NU Hosp Org, Dept Oral Maxillofacial Surg & Res & Dev, Trollhattan, Sweden..
    Thomsen, Peter
    BIOMATCELL VINN Excellence Ctr Biomat & Cell Ther, Gothenburg, Sweden.;Univ Gothenburg, Dept Biomat, Inst Clin Sci, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden..
    Omar, Omar
    BIOMATCELL VINN Excellence Ctr Biomat & Cell Ther, Gothenburg, Sweden.;Univ Gothenburg, Dept Biomat, Inst Clin Sci, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden..
    Guided bone regeneration using resorbable membrane and different bone substitutes: Early histological and molecular events2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 29, p. 409-423Article in journal (Refereed)
    Abstract [en]

    Bone insufficiency remains a major challenge for bone-anchored implants. The combination of guided bone regeneration (GBR) and bone augmentation is an established procedure to restore the bone. However, a proper understanding of the interactions between the bone substitute and GBR membrane materials and the bone-healing environment is lacking. This study aimed to investigate the early events of bone healing and the cellular activities in response to a combination of GBR membrane and different calcium phosphate (CaP) materials. Defects were created in the trabecular region of rat femurs, and filled with deproteinized bovine bone (DBB), hydroxyapatite (HA) or strontium-doped HA (SrHA) or left empty (sham). All the defects were covered with an extracellular matrix membrane. Defects were harvested after 12 h, 3 d and 6 d for histology/histomorphometry, immunohistochemistry and gene expression analyses. Histology revealed new bone, at 6 d, in all the defects. Larger amount of bone was observed in the SrHA-filled defect. This was in parallel with the reduced expression of osteoclastic genes (CR and CatK) and the osteoblast-osteoclast coupling gene (RANKL) in the SrHA defects. Immunohistochemistry indicated fewer osteoclasts in the SrHA defects. The observations of CD68 and periostin-expressing cells in the membrane per se indicated that the membrane may contribute to the healing process in the defect. It is concluded that the bone-promoting effects of Sr in vivo are mediated by a reduction in catabolic and osteoblast-osteoclast coupling processes. The combination of a bioactive membrane and CaP bone substitute material doped with Sr may produce early synergistic effects during GBR. Statement of significance The study provides novel molecular, cellular and structural evidence on the promotion of early bone regeneration in response to synthetic strontium-containing hydroxyapatite (SrHA) substitute, in combination with a resorbable, guided bone regeneration (GBR) membrane. The prevailing view, based mainly upon in vitro data, is that the beneficial effects of Sr are exerted by the stimulation of bone-forming cells (osteoblasts) and the inhibition of bone-resorbing cells (osteoclasts). In contrast, the present study demonstrates that the local effect of Sr in vivo is predominantly via the inhibition of osteoclast number and activity and the reduction of osteoblast-osteoclast coupling. This experimental data will form the basis for clinical studies, using this material as an interesting bone substitute for guided bone regeneration.

  • 6.
    Ginebra, Maria-Pau
    et al.
    Technical University of Catalonia.
    Montserrat, Espanol
    Technical University of Catalonia.
    Montufar, Edgar Benjamin
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering.
    Perez, Roman A
    Mestres, Gemma
    Technical University of Catalonia.
    New processing approaches in calcium phosphate cements and their applicationsin regenerative medicine2010In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 6, no 8, p. 2863-2873Article, review/survey (Refereed)
    Abstract [en]

    The key feature of calcium phosphate cements (CPCs) lies in the setting reaction triggered by mixing oneor more solid calcium phosphate salts with an aqueous solution. Upon mixture, the reaction takes placethrough a dissolution–precipitation process which is macroscopically observed by a gradual hardening ofthe cement paste. The precipitation of hydroxyapatite nanocrystals at body or room temperature, and the fact that those materials can be used as self-setting pastes, have for many years been the most attractivefeatures of CPCs. However, the need to develop materials able to sustain bone tissue ingrowth and be capable of delivering drugs and bioactive molecules, together with the continuous requirement from surgeons to develop more easily handling cements, has pushed the development of new processing routes that can accommodate all these requirements, taking advantage of the possibility of manipulating the self-setting CPC paste. It is the goal of this paper to provide a brief overview of the new processing developments in the area of CPCs and to identify the most significant achievements.

  • 7.
    Hulsart-Billström, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Hu, Qinghong
    Centre of Biopathways and Biomaterials, Dept of Chemistry, Zhejiang University, Hangzhou, Zhejiang, China .
    Bergman, Kristoffer
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Jonsson, Kenneth B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Åberg, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Tang, Ruikang
    Centre of Biopathways and Biomaterials, Dept of Chemistry, Zhejiang University, Hangzhou, Zhejiang, China .
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Calcium phosphates compounds in conjunction with hydrogel as carrier for BMP-2: A study on ectopic bone formation in rats2011In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 7, no 8, p. 3042-3049Article in journal (Refereed)
    Abstract [en]

    Current treatment of fractures often involves the use of bone graft or bone morphogenetic proteins (BMP) to induce fracture healing, especially in patients with a compromised healing capacity. BMP has to be delivered in conjunction with a carrier. Unfortunately, there are drawbacks and limitations with current carriers, including their bovine origin which carries the risk of an immunological response. The physical properties also limit the use to open surgical procedures, as it cannot be injected. New carriers with improved properties are therefore needed. The aim of this study was to assess the ectopic bone forming capability of various calcium phosphate compounds when used in conjunction with a hydrogel as the carrier for BMP-2. Five different ceramic additives were tested, including beta-tricalcium phosphate and four types of hydroxyapatite (HAP) (nanoHAP, HAP, clods of HAP >100 mu m, and the biomimetic HAP Ostim35 (R)). The compounds were injected into the thigh muscle of rats, where it formed a gel in situ. After 4 weeks bone formation was evaluated by peripheral quantitative computed tomography and histology. The major finding was that the 20 nm nanoHAP yielded a higher bone density than the other additives (P = 0.0008, ANOVA with Tukey's multiple comparison test). We hypothesize that the higher bone density induced by nanoHAP might be due to nanocrystals of calcium phosphate acting as direct building blocks for biomineralization.

  • 8.
    Jangamreddy, Jaganmohan R.
    et al.
    Dept. of Clinical and Experimental Medicine, Linköping University, S-58185 Linköping, Sweden; Tej Kohli Cornea Institute, LV Prasad Eye Institute, Hyderabad - 500 034, India.
    Haagdorens, Michel K.C.
    Dept. of Ophthalmology, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Antwerp, Belgium; Faculty of Medicine and Health Sciences, Department of Ophthalmology, Visual Optics and Visual Rehabilitation, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Antwerp, Belgium.
    Islam, M. Mirazul
    Dept. of Clinical and Experimental Medicine, Linköping University, S-58185 Linköping, Sweden.
    Lewis, Philip
    Structural Biophysics Group, School of Optometry and Vision Sciences, Cardiff University, Wales CF24 4HQ, UK.
    Samanta, Ayan
    Dept. of Clinical and Experimental Medicine, Linköping University, S-58185 Linköping, Sweden.
    Fagerholm, Per
    Dept. of Clinical and Experimental Medicine, Linköping University, S-58185 Linköping, Sweden.
    Liszka, Aneta
    Dept. of Clinical and Experimental Medicine, Linköping University, S-58185 Linköping, Sweden.
    Ljunggren, Monika K.
    Dept. of Clinical and Experimental Medicine, Linköping University, S-58185 Linköping, Sweden.
    Buznyk, Oleksiy
    Dept. of Clinical and Experimental Medicine, Linköping University, S-58185 Linköping, Sweden.
    Alarcon, Emilio I.
    Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y 4W7, Canada.
    Zakaria, Nadia
    Dept. of Ophthalmology, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Antwerp, Belgium; Faculty of Medicine and Health Sciences, Department of Ophthalmology, Visual Optics and Visual Rehabilitation, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Antwerp, Belgium .
    Meek, Keith M.
    Structural Biophysics Group, School of Optometry and Vision Sciences, Cardiff University, Wales CF24 4HQ, UK.
    Griffith, May
    Dept. of Clinical and Experimental Medicine, Linköping University, S-58185 Linköping, Sweden; Maisonneuve-Rosemont Hospital Research Centre and Dept. of Ophthalmology, University of Montreal, Montreal, QC H1T 4B3, Canada.
    Short peptide analogs as alternatives to collagen in pro-regenerative corneal implants2018In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 69, p. 120-130Article in journal (Refereed)
    Abstract [en]

    Short collagen-like peptides (CLPs) are being proposed as alternatives to full-length collagen for use in tissue engineering, on their own as soft hydrogels, or conjugated to synthetic polymer for mechanical strength. However, despite intended clinical use, little is known about their safety and efficacy, mechanism of action or degree of similarity to the full-length counterparts they mimic. Here, we show the functional equivalence of a CLP conjugated to polyethylene glycol (CLP-PEG) to full-length recombinant human collagen in vitro and in promoting stable regeneration of corneal tissue and nerves in a preclinical mini-pig model. We also show that these peptide analogs exerted their pro-regeneration effects through stimulating extracellular vesicle production by host cells. Our results support future use of CLP-PEG implants for corneal regeneration, suggesting the feasibility of these or similar peptide analogs in clinical application in the eye and other tissues.

  • 9.
    Janke, H. P.
    et al.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Urol..
    Bohlin, Jan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Lomme, R. M. L. M.
    Radboud Univ Nijmegen, Med Ctr, Dept Surg..
    Mihaila, S. M.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Urol..
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Feitz, W. F. J.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Urol.;Radboudumc Amalia Childrens Hosp..
    Oosterwijk, E.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, Dept Urol..
    Bioinspired coupled helical coils for soft tissue engineering of tubular structures: Improved mechanical behavior of tubular collagen type I templates2017In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 59, p. 234-242Article in journal (Refereed)
    Abstract [en]

    The design of constructs for tubular tissue engineering is challenging. Most biomaterials need to be reinforced with supporting structures such as knittings, meshes or electrospun material to comply with the mechanical demands of native tissues. In this study, coupled helical coils (CHCs) were manufactured to mimic collagen fiber orientation as found in nature. Monofilaments of different commercially available biodegradable polymers were wound and subsequently fused, resulting in right-handed and left-handed polymer helices fused together in joints where the filaments cross. CHCs of different polymer composition were tested to determine the tensile strength, strain recovery, hysteresis, compressive strength and degradation of CHCs of different composition. Subsequently, seamless and stable hybrid constructs consisting of PDSII (R) USP 2-0 CHCs embedded in porous collagen type I were produced. Compared to collagen alone, this hybrid showed superior strain recovery (93.5 +/- 0.9% vs 71.1 +/- 12.6% in longitudinal direction; 87.1 +/- 6.6% vs 57.2 +/- 4.6% in circumferential direction) and hysteresis (18.9 +/- 2.7% vs 51.1 +/- 12.0% in longitudinal direction; 11.5 +/- 4.6% vs 46.3 +/- 6.3% in circumferential direction). Furthermore, this hybrid construct showed an improved Young's modulus in both longitudinal (0.5 +/- 0.1 MPa vs 0.2 +/- 0.1 MPa; 2.5-fold) and circumferential (1.65 +/- 0.07 MPa vs (2.9 +/- 0.3) x 10(-2) MPa; 57-fold) direction, respectively, compared to templates created from collagen alone. Moreover, hybrid template characteristics could be modified by changing the CHC composition and CHCs were produced showing a mechanical behavior similar to the native ureter. CHC-enforced templates, which are easily tunable to meet different demands may be promising for tubular tissue engineering. Statement of Significance Most tubular constructs lack sufficient strength and tunability to comply with the mechanical demands of native tissues. Therefore, we embedded coupled helical coils (CHCs) produced from biodegradable polymers - to mimic collagen fiber orientation as found in nature - in collagen type I sponges. We show that the mechanical behavior of CHCs is very similar to native tissue and strengths structurally weak tubular constructs. The production procedure is relatively easy, reproducible and mechanical features can be controlled to meet different mechanical demands. This is promising in template manufacture, hence offering new opportunities in tissue engineering of tubular organs and preventing graft failure.

  • 10.
    Kennedy, Patrick J.
    et al.
    Univ Porto, i3S, Porto, Portugal;Univ Porto, INEB Inst Engn Biomed, Porto, Portugal;Univ Porto, IPATIMUP Inst Patol & Imunol Mol, Porto, Portugal;Univ Porto, ICBAS, Porto, Portugal.
    Sousa, Flavia
    Univ Porto, i3S, Porto, Portugal;Univ Porto, INEB Inst Engn Biomed, Porto, Portugal;Univ Porto, ICBAS, Porto, Portugal;Inst Invest & Formacao Avancada Ciencias & Tecnol, CESPU, Gandra, Portugal;Inst Univ Ciencias Saude, Gandra, Portugal.
    Ferreira, Daniel
    Univ Porto, i3S, Porto, Portugal;Univ Porto, IPATIMUP Inst Patol & Imunol Mol, Porto, Portugal.
    Pereira, Carla
    Univ Porto, i3S, Porto, Portugal;Univ Porto, IPATIMUP Inst Patol & Imunol Mol, Porto, Portugal.
    Nestor, Marika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Oliveira, Carla
    Univ Porto, i3S, Porto, Portugal;Univ Porto, IPATIMUP Inst Patol & Imunol Mol, Porto, Portugal;Univ Porto, FMUP Fac Med, Porto, Portugal.
    Granja, Pedro L.
    Univ Porto, i3S, Porto, Portugal;Univ Porto, INEB Inst Engn Biomed, Porto, Portugal;Univ Porto, ICBAS, Porto, Portugal;Univ Porto, FMUP Fac Med, Dept Engn Met & Mat, Porto, Portugal.
    Sarmento, Bruno
    Univ Porto, i3S, Porto, Portugal;Univ Porto, INEB Inst Engn Biomed, Porto, Portugal;Inst Invest & Formacao Avancada Ciencias & Tecnol, CESPU, Gandra, Portugal;Inst Univ Ciencias Saude, Gandra, Portugal;Queens Univ Belfast, Sch Pharm, Ctr Med Biol, Belfast, Antrim, North Ireland.
    Fab-conjugated PLGA nanoparticles effectively target cancer cells expressing human CD44v62018In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 81, p. 208-218Article in journal (Refereed)
    Abstract [en]

    Targeting of CD44 isoforms containing exon v6 (CD44v6) represents a viable strategy for the therapy and/or early diagnosis of metastatic cancers of the epithelium (e.g. gastric and colorectal cancer). We developed and characterized poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) modified with polyethylene glycol (PEG) and engrafted, by site-directed conjugation, with an engineered human Fab that specifically target human CD44v6 (v6 Fab-PLGA NPs). The v6 Fab-PLGA NPs displayed spherical morphology around 300 nm and were negatively charged. They strongly bound to a CD44v6-derived peptide and, more importantly, to cells that endogenously and exogenously express CD44v6, but not to non expressing cells and cells expressing the standard isoform of CD44. The v6 Fab-PLGA NPs also recognized CD44v6 in tumor sections from cells grown subcutaneously within mice. The NPs had nominal cytotoxicity at 50 mu g/mL and withstood simulated intestinal fluid exposure. Interestingly, v6 Fab-PLGA NPs cryopreserved in 10% trehalose and stored maintained specific cell binding. In conclusion, we envision NPs targeting CD44v6 as potential in vivo diagnostic agents and/or as anti-cancer agents in patients previously stratified with CD44v6(+) carcinomas. Statement of Significance The v6 Fab-PLGA NPs displayed many favorable qualities as a potential CD44v6-targeted drug and/or diagnostic delivery agent. The NPs were designed for optimal ligand orientation and for immediate administration into humans. v6 Fab-PLGA NPs strongly bound to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. Binding ability was retained after freeze-drying and long-term storage, providing evidences on the stability of Fab-functionalized NPs. These NPs can potentially be used as an in vivo diagnostic from parenteral or oral/rectal administration.

  • 11.
    Luo, Jun
    et al.
    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.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    A ready-to-use acidic, brushite-forming calcium phosphate cement2018In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 81, p. 304-314Article in journal (Refereed)
    Abstract [en]

    Premixed calcium phosphate cements have been developed to simplify the usage of traditional calcium phosphate cements and reduce the influence of the setting reaction on the delivery process. However, difficulties in achieving a good cohesion, adequate shelf life and sufficient mechanical properties have so far impeded their use in clinical applications, especially for the more degradable acidic calcium phosphate cements. In this study, a brushite cement was developed from a series of ready-to-use calcium phosphate pastes. The brushite cement paste was formed via mixing of a monocalcium phosphate monohydrate (MCPM) paste and a beta-tricalcium phosphate (beta-TCP) paste with good injectability and adequate shelf life. The MCPM paste was based on a water-immiscible liquid with two surfactants and the beta-Tcp paste on a sodium hyaluronate aqueous solution. The effect of citric acid as a retardant was assessed. Formulations with suitable amounts of citric acid showed good cohesion and mechanical performance with potential for future clinical applications. Statement of Significance Acidic calcium phosphate cements have attracted extensive attention as bone substitute materials due to their ability to resorb faster than basic calcium phosphate cements in vivo. However, traditionally, short working times and low mechanical strength have limited their clinical application. Premixed cements could simplify the clinical use as well as improve property reproducibility, but short shelf lives, low cohesion and low mechanical properties have restricted the development. In this study, an injectable ready-to-use two-phase system consisting of an MCPM paste and a beta-TCP paste was developed based on acidic cement. It shows good cohesion, compressive strength and adequate shelf life, which has the potential to be used in a dual chamber system for simplified and fast filling of bone defects in a minimally invasive manner. This will reduce surgery time, decrease the risk of contamination and ensure repeatable results.

  • 12.
    Mestres, Gemma
    et al.
    Technical University of Catalonia.
    Abdolhosseini, M.
    Bowles, W.
    Huang, S. -H.
    Aparicio, C.
    Gorr, S.-U.
    Ginebra, Maria-Pau
    Technical University of Catalonia.
    Antimicrobial properties and dentin bonding strength of magnesium phosphate cements2013In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 9, no 9, p. 8384-8393Article in journal (Refereed)
    Abstract [en]

    The main objective of this work was to assess the antimicrobial properties and the dentin-bonding strength of novel magnesium phosphate cements (MPC). Three formulations of MPC, consisting of magnesium oxide and a phosphate salt, NH4H2PO4, NaH2PO4 or a mixture of both, were evaluated. As a result of the setting reaction, MPC transformed into either struvite (MgNH4PO46H2O) when NH4H2PO4 was used or an amorphous magnesium sodium phosphate when NaH2PO4 was used. The MPC had appropriate setting times for hard tissue applications, high early compressive strengths and higher strength of bonding to dentin than commercial mineral trioxide aggregate cement. Bacteriological studies were performed with fresh and aged cements against three bacterial strains, Escherichia coli, Pseudomonas aeruginosa (planktonic and in biofilm) and Aggregatibacter actinomycetemcomitans. These bacteria have been associated with infected implants, as well as other frequent hard tissue related infections. Extracts of different compositions of MPC had bactericidal or bacteriostatic properties against the three bacterial strains tested. This was associated mainly with a synergistic effect between the high osmolarity and alkaline pH of the MPC. These intrinsic antimicrobial properties make MPC preferential candidates for applications in dentistry, such as root fillers, pulp capping agents and cavity liners.

  • 13.
    Mestres, Gemma
    et al.
    Technical University of Catalonia.
    Ginebra, Maria-Pau
    Technical University of Catalonia.
    Novel magnesium phosphate cements with high early strength and antibacterial properties2011In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 7, p. 1853-1861Article in journal (Refereed)
    Abstract [en]

    Magnesium phosphate cements (MPCs) have been extensively used as fast setting repair cements in civil engineering. They have properties that are also relevant to biomedical applications, such as fast setting, early strength acquisition and adhesive properties. However, there are some aspects that should be improved before they can be used in the human body, namely their highly exothermic setting reaction and the release of potentially harmful ammonia or ammonium ions. In this paper a new family of MPCs was explored as candidate biomaterials for hard tissue applications. The cements were prepared by mixing magnesium oxide (MgO) with either sodium dihydrogen phosphate (NaH2PO4) or ammonium dihydrogenphosphate (NH4H2PO4), or an equimolar mixture of both. The exothermia and setting kinetics of the new cement formulations were tailored to comply with clinical requirements by adjusting the granularity of the phosphate salt and by using sodium borate as a retardant. The ammonium-containing MPC resulted in struvite (MgNH4PO46H2O) as the major reaction product, whereas the MPC prepared with sodium dihydrogenphosphate resulted in an amorphous product. Unreacted magnesium oxide was found in all the formulations.The MPCs studied showed early compressive strengths substantially higher than that of apatitic calcium phosphate cements. The Na-containing MPCs were shown to have antibacterial activity against Streptococcus sanguinis, which was attributed to the alkaline pH developed during the setting reaction.

  • 14.
    Mestres, Gemma
    et al.
    Technical University of Catalonia.
    Le Van, Clemence
    Ginebra, Maria-Pau
    Technical University of Catalonia.
    Silicon-stabilized a-tricalcium phosphate and its use in a calcium phosphate cement: Characterization and cell response2012In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 8, no 3, p. 1169-1179Article in journal (Refereed)
    Abstract [en]

    a-Tricalcium phosphate (a-TCP) is widely used as a reactant in calcium phosphate cements. This work aims at doping a-TCP with silicon with a two-fold objective. On the one hand, to study the effect of Si addition on the stability and reactivity of this polymorph. On the other, to develop Si-doped cements and to evaluate the effect of Si on their in vitro cell response. For this purpose a calcium-deficient hydroxyapatite was sintered at 1250 C with different amounts of silicon oxide. The high temperature polymorpha-TCP was stabilized by the presence of silicon, which inhibited reversion of the b?a transformation, whereas in the Si-free sample a-TCP completely reverted to the b-polymorph. However, the b–a transformation temperature was not affected by the presence of Si. Si–a-TCP and its Si-free counterpart were used as reactants for a calcium phosphate cement. While Si–a-TCP showed faster hydrolysis to calcium deficient hydroxyapatite, upon complete reaction the crystalline phases, morphology and mechanical properties of both cements were similar. An in vitro cell culture study, in which osteoblast-like cells were exposed to the ions released by both materials, showed a delay in cell proliferation in both cases and stimulation of cell differentiation, more marked for the Si-containing cement. These results can be attributed to strong modification of the ionic concentrations in the culture medium by both materials. Ca depletion from the medium was observed for both cements, whereas continuous Si release was detected for the Si-containing cement.

  • 15.
    Mestres, Gemma
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Santos, Carlos F
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engman, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Scavenging effect of Trolox released from brushite cements2015In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 11, p. 459-466Article in journal (Refereed)
    Abstract [en]

    In this study a brushite cement was doped with the chain-breaking antioxidant Trolox. The effect of the antioxidant on the physical properties of the cement was evaluated and the release of Trolox was monitored by UV spectroscopy. The ability of the Trolox set free to scavenge reactive oxygen species (ROS) released by macrophages was determined in vitro using a luminol-amplified chemiluminescence assay. Trolox did not modify the crystalline phases of the set cement, which mainly formed crystalline brushite after 7days in humid conditions. The setting time, compressive strength and morphology of the cement also remained unaltered after the addition of the antioxidant. Trolox was slowly released from the cement following a non-Fickian transport mechanism and nearly 64% of the total amount was released after 3days. Moreover, the capacity of Trolox to scavenge the ROS released by macrophages increased in a dose-dependent manner. Trolox-loaded cements are expected to reduce some of the first harmful effects of acute inflammation and can thus potentially protect the surrounding tissue during implantation of these as well as other materials used in conjunction.

  • 16. Mirazul Islam, M
    et al.
    Cėpla, Vytautas
    He, Chaoliang
    Edin, Joel
    Rakickas, Tomas
    Kobuch, Karin
    Ruželė, Živilė
    Bruce Jackson, W
    Rafat, Mehrdad
    Lohmann, Chris P
    Valiokas, Ramūnas
    Griffith, May
    Functional fabrication of recombinant human collagen-phosphorylcholine hydrogels for regenerative medicine applications.2015In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 12, p. 70-80, article id S1742-7061(14)00486-3Article in journal (Refereed)
    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.

  • 17.
    Montazerolghaem, Maryam
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Nyström, Lina
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Zebrafish: A possible tool to evaluate bioactive ions2015In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 19, p. 10-14Article in journal (Refereed)
    Abstract [en]

    Zebrafish is a well-established model organism with a skeletal structure that highly resembles mammalian bone. Yet its use in the research field of biomaterials has been limited. One area that could benefit from this model system is the evaluation of ionic dissolution products from different materials. As a proof of concept we have evaluated the effect of silicate ions on the zebrafish larvae and compared it to a well-known osteblastic cell line, MC3T3-E1 subclone 14. We have shown that sodium metasilicate (125 mu M and 625 mu M) induces more mineralisation in a dose-dependent manner in zebrafish larvae, 9 days post fertilisation as compared to the non-treated group. Moreover the same trends were seen when adding sodium metasilicate to MC3T3-E1 cultures, with more mineralisation and higher ALP levels with higher doses of silicate (25, 125 and 625 mu M). These results indicate the feasibility of zebrafish larvae for ionic dissolution studies. The zebrafish model is superior to isolated cell cultures in the aspect that it includes the whole bone remodelling system, with osteoblasts, osteoclasts and osteocytes. Zebrafish could thus provide a powerful in vivo tool and be a bridge between cell culture systems and mammalian models.

  • 18.
    Offermanns, Vincent
    et al.
    Department of Cranio-, Maxillofacial and Oral Surgery, Medical University Innsbruck, Austria.
    Andersen, Ole
    Interdisciplinary Nanoscience Center (iNANO), Faculty of Science and Technology, Aarhus University, Denmark.
    Riede, Gregor
    Department of Cranio-, Maxillofacial and Oral Surgery, Medical University Innsbruck, Austria.
    Sillassen, Michael
    Interdisciplinary Nanoscience Center (iNANO), Faculty of Science and Technology, Aarhus University, Denmark.
    Jeppesen, Christian
    Tribology Centre, Danish Technological Institute, Aarhus, Denmark.
    Almtoft, Klaus
    Tribology Centre, Danish Technological Institute, Aarhus, Denmark.
    Talasz, Heribert
    Biocenter, Division of Clinical Biochemistry, Medical University Innsbruck, Austria.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Lethaus, Bernd
    Department of Cranio-, Maxillofacial and Oral Surgery, RTWH Aachen, Germany.
    Tolba, Rene
    Central Laboratory Animal Facility, RTWH Aachen, Germany.
    Kloss, Frank
    Private Practice, Lienz, Austria.
    Foss, Morten
    Department of Physics and Astronomy, Faculty of Science and Technology, Aarhus University, Denmark.
    Effect of strontium surface-functionalized implants on early and late osseointegration: A histological, spectrometric and tomographic evaluation2018In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 69, p. 385-394Article in journal (Refereed)
    Abstract [en]

    Energy efficient sensing is one of the main objectives in the design of networked embedded monitoring systems. However, existing approaches such as duty cycling and ambient energy harvesting face challenges in railway bridge health monitoring applications due to the unpredictability of train passages and insufficient ambient energy around bridges. This paper presents ECOVIBE (Eco-friendly Vibration), an on-demand sensing system that automatically turns on itself when a train passes on the bridge and adaptively powers itself off after finishing all tasks. After that, it goes into an inactive state with near-zero power dissipation. ECOVIBE achieves these by: Firstly, a novel, fully passive event detection circuit to continuously detect passing trains without consuming any energy. Secondly, combining train-induced vibration energy harvesting with a transistor-based load switch, a tiny amount of energy is sufficient to keep ECOVIBE active for a long time. Thirdly, a passive adaptive off control circuit is introduced to quickly switch off ECOVIBE. Also this circuit does not consume any energy during inactivity periods. We present the prototype implementation of the proposed system using commercially available components and evaluate its performance in real-world scenarios. Our results show that ECOVIBE is effective in railway bridge health monitoring applications.

  • 19.
    Robo, Céline
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Hulsart Billström, Gry
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Nilsson, Malin
    Inossia AB, Stockholm, Sweden.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    In vivo response to a low-modulus PMMA bone cement in an ovine model2018In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 72, p. 362-370Article in journal (Refereed)
    Abstract [en]

    Poly(methyl methacrylate) (PMMA) is the most commonly used material for the treatment of osteoporosis-induced vertebral compression fractures. However, its high stiffness may introduce an increased risk of adjacent vertebral fractures post-surgery. One alternative in overcoming this concern is the use of additives. This presents its own challenge in maintaining an adequate biocompatibility when modifying the base cement. The aim of this study was to evaluate the in vivobiocompatibility of linoleic acid (LA)-modified acrylic bone cement using a large animal model for the first time, in order to further advance towards clinical use. A worst-case approach was used, choosing a slow-setting base cement. The in vitro monomer release from the cements was also assessed. Additional material characterization, including mechanical tests, are summarized in Appendix A. Unmodified and LA-modified cements were injected into a total of 56 bone defects created in the femur and humerus of sheep. Histopathologic and histomorphometric analysis indicated that LA-modified cement showed a harmless tissue response similar to that of the unmodified cement. Adjacent bone remodeling was observed microscopically 4 weeks after implantation, suggesting a normal healing process of the bone tissues surrounding the implant. LA-modified cement exhibited lower mechanical properties, with a reduction in the elastic modulus of up to 65%. The handling properties were slightly modified without negatively affecting the injectability of the base cement. LA-modified bone cement showed good biocompatibility as well as bone compliant mechanical properties and may therefore be a promising material for the treatment of osteoporotic vertebral fractures. 

  • 20. Stenlund, Patrik
    et al.
    Omar, Omar
    Brohede, Ulrika
    Norgren, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Norlindh, Birgitta
    Johansson, Anna
    Lausmaa, Jukka
    Thomsen, Peter
    Palmquist, Anders
    Bone response to a novel Ti–Ta–Nb–Zr alloy2015In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 20, p. 165-175Article in journal (Refereed)
  • 21. Stenlund, Patrik
    et al.
    Omar, Omar
    Brohede, Ulrika
    Norgren, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Norlindh, Birgitta
    Johansson, Anna
    Lausmaa, Jukka
    Thomsen, Peter
    Palmquist, Anders
    Bone response to a novel Ti-Ta-Nb-Zr alloy2015In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 20, p. 165-175Article in journal (Refereed)
    Abstract [en]

    Commercially pure titanium (cp-Ti) is regarded as the state-of-the-art material for bone-anchored dental devices, whereas the mechanically stronger alloy (Ti-6Al-4V), made of titanium, aluminum (Al) and vanadium (V), is regarded as the material of choice for high-load applications. There is a call for the development of new alloys, not only to eliminate the potential toxic effect of Al and V but also to meet the challenges imposed on dental and maxillofacial reconstructive devices, for example. The present work evaluates a novel, dual-stage, acid-etched, Ti-Ta-Nb-Zr alloy implant, consisting of elements that create low toxicity, with the potential to promote osseointegration in vivo. The alloy implants (denoted Ti-Ta-Nb-Zr) were evaluated after 7 days and 28 days in a rat tibia model, with reference to commercially pure titanium grade 4 (denoted Ti). Analyses were performed with respect to removal torque, histomorphometry and gene expression. The Ti-Ta-Nb-Zr showed a significant increase in implant stability over time in contrast to the Ti. Further, the histological and gene expression analyses suggested faster healing around the Ti-Ta-Nb-Zr, as judged by the enhanced remodeling, and mineralization, of the early-formed woven bone and the multiple positive correlations between genes denoting inflammation, bone formation and remodeling. Based on the present experiments, it is concluded that the Ti-Ta-Nb-Zr alloy becomes osseointegrated to at least a similar degree to that of pure titanium implants. This alloy is therefore emerging as a novel implant material for clinical evaluation.

  • 22.
    Tang, Xiang-long
    et al.
    Nanjing Tech Univ, Coll Mat Sci & Engn, Nanjing 210009, Jiangsu, Peoples R China.
    Wu, Jun
    Nanjing Tech Univ, Coll Mat Sci & Engn, Nanjing 210009, Jiangsu, Peoples R China.
    Li, Ben-lan
    Nanjing Tech Univ, Coll Mat Sci & Engn, Nanjing 210009, Jiangsu, Peoples R China.
    Cui, Sheng
    Nanjing Tech Univ, Coll Mat Sci & Engn, Nanjing 210009, Jiangsu, Peoples R China.
    Liu, Hong-mei
    Xuzhou Med Univ, Affiliated Hosp, Brain Hosp, Xuzhou, Jiangsu, Peoples R China.
    Yu, Ru-tong
    Xuzhou Med Univ, Affiliated Hosp, Brain Hosp, Xuzhou, Jiangsu, Peoples R China.
    Shen, Xiao-dong
    Nanjing Tech Univ, Coll Mat Sci & Engn, Nanjing 210009, Jiangsu, Peoples R China.
    Wang, Ting-wei
    Nanjing Tech Univ, Coll Mat Sci & Engn, Nanjing 210009, Jiangsu, Peoples R China.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Near-infrared light-activated red-emitting upconverting nanoplatform for T-1-weighted magnetic resonance imaging and photodynamic therapy2018In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 74, p. 360-373Article in journal (Refereed)
    Abstract [en]

    Photodynamic therapy (PDT) has increasingly become an efficient and attractive cancer treatment modality based on reactive oxygen species (ROS) that can induce tumor death after irradiation with ultraviolet or visible light. Herein, to overcome the limited tissue penetration in traditional PDT, a novel near-infrared (NIR) light-activated NaScF4: 40% Yb, 2% Er@CaF2 upconversion nanoparticle (rUCNP) is successfully designed and synthesized. Chlorin e6, a photosensitizer and a chelating agent for Mn2+, is loaded into human serum albumin (HSA) that further conjugates onto rUCNPs. To increase the ability to target glioma tumor, an acyclic Arg-Gly-Asp peptide (cRGDyK) is linked to rUCNPs@HSA(Ce6-Mn). This nanoplatform enables efficient adsorption and conversion of NIR light (980 nm) into bright red emission (660 nm), which can trigger the photosensitizer Ce6-Mn complex for PDT and T-1-weighted magnetic resonance imaging (T-1-weighted MRI) for glioma diagnosis. Our in vitro and in vivo experiments demonstrate that NIR light-activated and glioma tumor-targeted PDT can generate large amounts of intracellular ROS that induce U87 cell apoptosis and suppress glioma tumor growth owing to the deep tissue penetration of irradiated light and excellent tumor-targeting ability. Thus, this nanoplatform holds potential for applications in T-1-weighted MRI diagnosis and PDT of glioma for antitumor therapy. Statement of Significance A near-infrared (NIR) light-activated nanoplatform for photodynamic therapy (PDT) was designed and synthesized. The Red-to-Green (RIG) ratio of NaScF4: 40% Yb, 2% Er almost reached 9, a value that was much higher than that of a traditional Yb/Er-codoped upconversion nanoparticle (rUCNP). By depositing a CaF2 shell, the red-emission intensities of the rUCNPs were seven times strong as that of NaScF4: 40% Yb, 2% Er. The enhanced red-emitting rUCNPs could be applied in many fields such as bioimaging, controlled release, and real-time diagnosis. The nanoplatform had a strong active glioma-targeting ability, and all results achieved on subcutaneous glioma demonstrated that our NIR light-activated redemitting upconverting nanoplatform was efficient for PDT. By loading Ce6-Mn complex into rUCNPs@HSA-RGD, the nanoplatform could be used as a T-1-weighted magnetic resonance imaging agent for tumor diagnosis.

  • 23.
    Thorfve, Anna
    et al.
    University of Gothenburg.
    Lindahl, Carl
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Igawa, Kazuyo
    Southern Tohoku General Hospital.
    Lindahl, Anders
    University of Gothenburg.
    Thomsen, Peter
    Gothenburg University.
    Palmqvist, Anders
    Gothenburg University.
    Tengvall, Pentti
    University of Gothenburg.
    Hydroxyapatite coating affects the Wnt signaling pathway during peri-implant healing in vivo2014In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 10, no 3, p. 1451-1462Article in journal (Refereed)
    Abstract [en]

    Owing to its bio- and osteoconductivity, hydroxyapatite (HA) is a widely used implant material, but its osteogenic properties are only partly evaluated in vitro and in vivo. The present study focused on bone healing adjacent to HA-coated titanium (Ti) implants, with or without incorporated lithium ions (Li+). Special attention was given to the Wnt signaling pathway. The implants were inserted into rat tibia for 7 or 28 days and analyzed ex vivo, mainly by histomorphometry and quantitative real-time polymerase chain reaction (qPCR). HA-coated implants showed, irrespective of Li+ content, bone-implant contact (BIC) and removal torque values significantly higher than those of reference Ti. Further, the expression of OCN, CTSK, COL1A1, LRP5/6 and WISP1 was significantly higher in implant-adherent cells of HA-coated implants, with or without Li+. Significantly higher beta-catenin expression and significantly lower COL2A1 expression were observed in pen-implant bone cells from HA with 14 ng cm(-2) released Li+. Interestingly, Ti implants showed a significantly larger bone area (BA) in the threads than HA with 39 ng cm(-2) released Li+, but had a lower BIC than any HA-coated implant. This study shows that HA, with or without Li+, is a strong activator of the Wnt signaling pathway, and may to some degree explain its high bone induction capacity.

  • 24.
    Unosson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Rodriguez, Daniel
    Technical University of Catalonia.
    Welch, Ken
    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.
    Reactive combinatorial synthesis and characterization of a gradient Ag–Ti oxide thin film with antibacterial properties2015In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 11, p. 503-510Article in journal (Refereed)
    Abstract [en]

    The growing demand for orthopedic and dental implants has spurred researchers to develop multifunc- tional coatings, combining tissue integration with antibacterial features. A possible strategy to endow titanium (Ti) with antibacterial properties is by incorporating silver (Ag), but designing a structure with adequate Ag+ release while maintaining biocompatibility has been shown difficult. To further explore the composition–structure–property relationships between Ag and Ti, and its effects against bacteria, this study utilized a combinatorial approach to manufacture and test a single sample containing a binary Ag–Ti oxide gradient. The sample, sputter-deposited in a reactive (O2) environment using a custom-built combinatorial physical vapor deposition system, was shown to be effective against Staphylococcus aureus with viability reductions ranging from 17 to above 99%, depending on the amount of Ag+ released from its different parts. The Ag content along the gradient ranged from 35 to 62 wt.%, but it was found that structural properties such as varied porosity and degree of crystallinity, rather than the amount of incor- porated Ag, governed the Ag+ release and resulting antibacterial activity. The coating also demonstrated in vitro apatite-forming abilities, where structural variety along the sample was shown to alter the hydrophilic behavior, with the degree of hydroxyapatite deposition varying accordingly. By means of combinatorial synthesis, a single gradient sample was able to display intricate compositional and structural features affecting its biological response, which would otherwise require a series of coatings. The current findings suggest that future implant coatings incorporating Ag as an antibacterial agent could be structurally enhanced to better suit clinical requirements. 

  • 25. Varga, Peter
    et al.
    Pacureanu, Alexandra
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Langer, Max
    Suhonen, Heikki
    Hesse, Bernhard
    Grimal, Quentin
    Cloetens, Peter
    Raum, Kay
    Peyrin, Françoise
    Investigation of the three-dimensional orientation of mineralized collagen fibrils in human lamellar bone using synchrotron X-ray phase nano-tomography2013In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 9, no 9, p. 8118-8127Article in journal (Refereed)
    Abstract [en]

    We investigate the three-dimensional (3-D) organization of mineralized collagen fibrils in human cortical bone based on synchrotron X-ray phase nano-tomography images. In lamellar bone the collagen fibrils are assumed to have a plywood-like arrangement, but due to experimental limitations the 3-D fibril structure has only been deduced from section surfaces so far and the findings have been controversial. Breakthroughs in synchrotron tomographic imaging have given access to direct 3-D information on the bone structure at the nanoscale level. Using an autocorrelation-based orientation measure we confirm that the fibrils are unidirectional in quasi-planes of sub-lamellae and find two specific dominant patterns, oscillating and twisted plywoods coexisting in a single osteon. Both patterns exhibit smooth orientation changes between adjacent quasi-planes. Moreover, we find that the periodic changes in collagen fibril orientation are independent of fluctuations in local mass density. These data improve our understanding of the lamellar arrangement in bone and allow more detailed investigations of structure-function relationships at this scale, providing templates for bio-inspired materials. The presented methodology can be applied to non-destructive 3-D characterization of the sub-micron scale structure of other natural and artificial mineralized biomaterials. 

  • 26.
    Wu, Dan
    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.
    Ferguson, Stephen
    ETH Zurich, Switzerland.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Young’s modulus of trabecular bone at the tissue level: A review2018In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 78, p. 1-12Article, review/survey (Refereed)
    Abstract [en]

    The tissue-level Young’s modulus of trabecular bone is important for detailed mechanical analysis of bone and bone-implant mechanical interactions. However, the heterogeneity and small size of the trabecular struts complicate an accurate determination. Methods such as micro-mechanical testing of single trabeculae, ultrasonic testing, and nanoindentation have been used to estimate the trabecular Young’s modulus. This review summarizes and classifies the trabecular Young’s moduli reported in the literature. Information on species, anatomic site, and test condition of the samples has also been gathered. Advantages and disadvantages of the different methods together with recent developments are discussed, followed by some suggestions for potential improvement, for future work. In summary, this review provides a thorough introduction to the approaches used for determining trabecular Young’s modulus, highlights important considerations when applying these methods and summarizes the reported Young’s modulus for follow-up studies on trabecular properties.

    The full text will be freely available from 2020-08-05 12:40
  • 27.
    Yoshihara, Akifumi
    et al.
    Univ Tokyo, Dept Bioengn, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan..
    Sekine, Ryota
    Univ Tokyo, Dept Bioengn, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan..
    Ueki, Takayuki
    Univ Tokyo, Dept Bioengn, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan..
    Kondo, Yasuhito
    Gunma Prefectural Text Ind Lab, 5-46-1 Aioicho, Kiryu, Gumma 3760011, Japan..
    Sunaga, Yoshiyuki
    Yanase Sangyosya, Midori Ku, 2703-1 Kasakakechosika, Gunma 3792313, Japan..
    Nakaji-Hirabayashi, Tadashi
    Univ Toyama, Grad Sch Sci & Engn, Dept Appl Chem, Toyama 9308555, Japan.;Univ Toyama, Frontier Res Core Life Sci, Toyama 9308555, Japan..
    Teramura, Yuji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Univ Tokyo, Dept Bioengn, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan. .
    Takai, Madoka
    Univ Tokyo, Dept Bioengn, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan..
    Rapid and highly efficient capture and release of cancer cells using polymeric microfibers immobilized with enzyme-cleavable peptides2018In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 67, p. 32-41Article in journal (Refereed)
    Abstract [en]

    Circulating tumor cells (CTCs) are tumor cells present in the blood. CTCs have attracted much attention as a new tumor marker, because their analysis provides useful information for monitoring cancer progress. In this study, we developed cell-capture and release methods using three-dimensional (3D) microfiber fabrics without damaging the cells. Using functional peptides containing sequences from a polystyrene-binding site and a cleavable site for collagenase type IV, immobilized antibodies on the peptides were able to specifically capture MCF-7 cells in a few minutes and release the captured cells from 3D microfiber fabrics incorporating a vacuum system. The efficiency of cell capture was around 80% and that of the cell release was over 90%. The released cells proliferated normally in culture medium, suggesting that our system will be applicable for the culture and analysis of CTCs. Statement of Significance In this paper, we report cell-capture and release methods using enzyme-cleavable peptides immobilized on microfiber fabrics which has microporous polymeric three-dimensional structures. Detachment and collection of the selectively captured cancer cells are required for ex vivo culture and their further analysis, whereas the cell detachment methods developed so far might cause cell damage, even if cell viability is high enough. Therefore, specific attachment and gentle detachment from the device are required for the accurate analysis of cells. In this study, for capture and release of cancer cells we designed the peptide cleavable by collagenase type IV, which has no target molecule in cells. Our system will be useful for further CTC analysis and might lead to more accurate cancer diagnosis.

  • 28.
    ZHANG, YU
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Heher, Philipp
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Austrian Cluster for Tissue Regeneration, Ludwig Boltzmann Institute for Experimental and Clinical Traumatology.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Redl, Heinz
    g Boltzmann Institute for Experimental and Clinical Traumatology.
    Ossipov, Dmitri
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Hyaluronic acid-fibrin interpenetrating double network hydrogelprepared in situ by orthogonal disulfide cross-linking reaction forbiomedical applications2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568Article in journal (Refereed)
  • 29.
    Zhang, Yu
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Heher, Philipp
    Ludwig Boltzmann Inst Expt & Clin Traumatol, Austrian Cluster Tissue Regenerat, Donaueschingenstr 13, A-1200 Vienna, Austria.;Trauma Care Consult GmbH, Gonzagagasse 11-25, A-1010 Vienna, Austria..
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Redl, Heinz
    Ludwig Boltzmann Inst Expt & Clin Traumatol, Austrian Cluster Tissue Regenerat, Donaueschingenstr 13, A-1200 Vienna, Austria.;Trauma Care Consult GmbH, Gonzagagasse 11-25, A-1010 Vienna, Austria..
    Ossipov, Dmitri A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Hyaluronic acid-fibrin interpenetrating double network hydrogel prepared in situ by orthogonal disulfide cross-linking reaction for biomedical applications2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 38, p. 23-32Article in journal (Refereed)
    Abstract [en]

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

  • 30.
    Zhang, Yu
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Rossi, Filippo
    Politecn Milan, Dept Chem Mat & Chem Engn Giulio Natta, Via Mancinelli, I-20131 Milan, Italy..
    Papa, Simonetta
    IRCCS Ist Ric Farmacol Mario Negri, Dept Neurosci, Via La Masa 19, I-20156 Milan, Italy..
    Violatto, Martina Bruna
    IRCCS Ist Ric Farmacol Mario Negri, Dept Biochem & Mol Pharmacol, Via La Masa 19, I-20156 Milan, Italy..
    Bigini, Paolo
    IRCCS Ist Ric Farmacol Mario Negri, Dept Biochem & Mol Pharmacol, Via La Masa 19, I-20156 Milan, Italy..
    Sorbona, Marco
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Redaelli, Francesca
    Veglianese, Pietro
    IRCCS Ist Ric Farmacol Mario Negri, Dept Neurosci, Via La Masa 19, I-20156 Milan, Italy..
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Ossipov, Dmitri A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Non-invasive in vitro and in vivo monitoring of degradation of fluorescently labeled hyaluronan hydrogels for tissue engineering applications2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 30, p. 188-198Article in journal (Refereed)
    Abstract [en]

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

1 - 30 of 30
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf