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  • 251.
    Pujari-Palmer, Shiuli
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Chen, Song
    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.
    Rubino, Stefano
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Weng, H
    Department of Biomedical Engineering, University of Texas at Arlington.
    Tang, Liping
    Department of Biomedical Engineering, University of Texas at Arlington.
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Influence of hydroxyapatite nanoparticle morphology on inflammatory response2015In: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, Vol. 29Article in journal (Refereed)
  • 252.
    Pujari-Palmer, Shiuli
    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.
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Reduced oxidative stress in primary human cells by antioxidant released from nanoporous alumina2016In: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981, Vol. 104, no 3, p. 568-575Article in journal (Refereed)
    Abstract [en]

    Nanoporous alumina elicits different inflammatory responses dependent on pore size, such as increased complement activation and reactive oxygen species (ROS) production, on 200 versus 20 nm pores. In this study, we attempt to further modulate inflammatory cell response by loading nanoporous alumina membranes (20, 100, and 200 nm pores), with an antioxidant, Trolox, for controlled drug release. For mononuclear cells (MNC) no difference in cell response, due to pore size, was seen when cultured on nonloaded membranes. However, when exposed to membranes loaded with Trolox, 100 uM was enough to quench ROS by more than 95% for all pore sizes. Polymorphonuclear cells (PMNC) produced significantly more ROS when exposed to 20 versus 100 nm pores. For Trolox loaded membranes, this trend reversed, due to slower release of antioxidant from the 20 nm pores. Furthermore, Trolox exhibited a unique effect on PMNCs that has not previously been reported: It delayed the production of ROS in a manner distinct from antioxidant activity. The present study confirms that nanoporous alumina is a suitable vehicle for drug delivery, and that Trolox can successfully modulate the inflammatory response of both MNC and PMNCs.

  • 253.
    Pulkkinen, Hertta
    et al.
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Tiitu, Virpi
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Lammentausta, Eveliina
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Laasanen, Mikko
    Department of Physics, University of Kuopio, Kuopio, Finland.
    Hämäläinen, Eija-Riitta
    Bioprocess Engineerng Laboratory, Department of Process and Environmental Engineering, University of Oulu, Oulu, Finland.
    Kiviranta, Ilkka
    Jyväskylä Central Hospital, Jyväskylä, Finland.
    Lammi, Mikko
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland.
    Cellulose sponge as a scaffold for cartilage tissue engineering.2006In: Bio-medical materials and engineering, ISSN 0959-2989, E-ISSN 1878-3619, Vol. 16, no 4 Suppl, p. S29-S35, article id 16823110Article in journal (Refereed)
    Abstract [en]

    One goal of functional tissue engineering is to manufacture scaffolds infiltrated with chondrocytes which are suitable for transplantation into the lesion areas of articular cartilage. Various research strategies are used to fabricate cartilage transplants which would have the correct phenotype, contain enough extracellular matrix components, and have structural and biomechanical properties equivalent to normal articular cartilage. We have investigated the suitability of viscose cellulose sponges as a scaffold for cartilage tissue engineering. The sponges were tested alone, or with recombinant human type II collagen cross-linked inside the material. Scanning electron microscopy and confocal microscopy were used to study the structure of the scaffold during four weeks of cultivation. Cellulose and cellulose/recombinant type II collagen sponges were biocompatible for at least four weeks in cultivation, and gradual filling of the scaffold was observed. However, the constructs remained soft during the observation period, and were devoid of extracellular matrix composition typical for normal articular cartilage.

  • 254.
    Pulkkinen, Hertta
    et al.
    Institute of Biomedicine, Anatomy, University of Eastern Finland, Kuopio, Finland.
    Tiitu, Virpi
    Institute of Biomedicine, Anatomy, University of Eastern Finland, Kuopio, Finland.
    Valonen, Pia
    Institute of Biomedicine, Anatomy, University of Eastern Finland, Kuopio, Finland.
    Jurvelin, Jukka
    Department of Physics and Mathematics, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Department of Biosciences, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Kiviranta, Ilkka
    Department of Orthopaedics and Traumatology, University of Helsinki, Helsinki, Finland; Department of Orthopaedics and Traumatology, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Engineering of cartilage in recombinant human type II collagen gel in nude mouse model in vivo.2010In: Osteoarthritis and Cartilage, ISSN 1063-4584, E-ISSN 1522-9653, Vol. 18, no 8, p. 1077-1087, article id 20472086Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Our goal was to test the recombinant human type II collagen (rhCII) material as a gel-like scaffold for chondrocytes in a nude mouse model in vivo.

    DESIGN: Isolated bovine chondrocytes (6x10(6)) were seeded into rhCII gels (rhCII-cell) and injected subcutaneously into the backs of nude mice. For comparison, chondrocytes (6x10(6)) in culture medium (Med-cell) and cell-free rhCII gels (rhCII-gel) were similarly injected (n=24 animals, total of three injections/animal). After 6 weeks, the tissue constructs were harvested and analyzed.

    RESULTS: Chondrocytes with or without rhCII-gel produced white resilient tissue, which in histological sections had chondrocytes in lacunae-like structures. Extracellular matrix stained heavily with toluidine blue stain and had strongly positive collagen type II immunostaining. The tissue did not show any evidence of vascular invasion or mineralization. The cell-free rhCII-gel constructs showed no signs of cartilage tissue formation. Cartilage tissue produced by Med-cell was thin and macroscopically uneven, while the rhCII-cell construct was smooth and rounded piece of neotissue. RhCII-cell constructs were statistically thicker than Med-cell ones. However, no statistical differences were found between the groups in terms of glycosaminoglycan (GAG) content or biomechanical properties.

    CONCLUSIONS: These results show that rhCII-gel provides good expansion and mechanical support for the formation of cartilage neotissue. RhCII material may allow favorable conditions in the repair of chondral lesions.

  • 255.
    Pulkkinen, Hertta
    et al.
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland; Department of Orthopaedics and Traumatology, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Tiitu, Virpi
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland; Department of Orthopaedics and Traumatology, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Valonen, Piia
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland; Department of Orthopaedics and Traumatology, Jyväskylä Central Hospital, Jyväskylä, Finland.
    Hämäläinen, Eija-Riitta
    Bioprocess Engineering Laboratory, University of Oulu, Oulu, Finland.
    Lammi, Mikko
    Institute of Biomedicine, Department of Anatomy, University of Kuopio, Kuopio, Finland; Department of Biosciences, Applied Biotechnology, University of Kuopio, Kuopio, Finland.
    Kiviranta, Ilkka
    Department of Orthopaedics and Traumatology, Jyväskylä Central Hospital, Jyväskylä, Finland; Department of Orthopaedics and Traumatology, Helsinki University Hospital, Helsinki, Finland.
    Recombinant human type II collagen as a material for cartilage tissue engineering.2008In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 31, no 11, p. 960-969, article id 19089798Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Collagen type II is the major component of cartilage and would be an optimal scaffold material for reconstruction of injured cartilage tissue. In this study, the feasibility of recombinant human type II collagen gel as a 3-dimensional culture system for bovine chondrocytes was evaluated in vitro.

    METHODS: Bovine chondrocytes (4x106 cells) were seeded within collagen gels and cultivated for up to 4 weeks. The gels were investigated with confocal microscopy, histology, and biochemical assays.

    RESULTS: Confocal microscopy revealed that the cells maintained their viability during the entire cultivation period. The chondrocytes were evenly distributed inside the gels, and the number of cells and the amount of the extracellular matrix increased during cultivation. The chondrocytes maintained their round phenotype during the 4-week cultivation period. The glycosaminoglycan levels of the tissue increased during the experiment. The relative levels of aggrecan and type II collagen mRNA measured with realtime polymerase chain reaction (PCR) showed an increase at 1 week.

    CONCLUSION: Our results imply that recombinant human type II collagen is a promising biomaterial for cartilage tissue engineering, allowing homogeneous distribution in the gel and biosynthesis of extracellular matrix components.

  • 256.
    Pöllänen, Raimo
    et al.
    BioMater Center, University of Eastern Finland, Kuopio, Finland.
    Tikkanen, Anna-Maria
    BioMater Center, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Department of Biomedicine, University of Eastern Finland, Kuopio, Finland; Department of Biosciences, Applied Biotechnology, University of Eastern Finland, Kuopio, Finland.
    Lappalainen, Reijo
    BioMater Center, University of Eastern Finland, Kuopio, Finland; Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    The effect of loading and material on the biomechanical properties and vitality of bovine cartilage in vitro.2011In: Journal of Applied Biomaterials and Biomechanics, ISSN 1722-6899, Vol. 9, no 1, p. 47-53, article id 21445828Article in journal (Refereed)
    Abstract [en]

    PURPOSE: New methodology for long-term (270 h) biomechanical testing with living cartilage was developed. Polyurethane (PU) implant material was compared with stainless steel and reference samples in static unconfined compressive loading conditions on cartilage to provide a basis for dynamic testing of novel PU implant materials under conditions that simulate an articulating human knee joint.

    METHODS: Custom-made tools and techniques were developed to prepare cylindrical samples from bovine patella with cartilage including subchondral bone. Specific incubator cups with static loading setups for a culture incubator were manufactured to keep bovine cartilage explants alive in cell culture conditions under unconfined static compressive loading (0.25 MPa) for 270 h (11.25 d). Four loading conditions of cartilage were studied: free (FREE), restrained minimal loading (RESTR), loading with a metal plate (MEW) and loading with polyurethane (PUW).

    RESULTS: After static loading for 270 h, cartilage biomechanical tests indicated clear differences between the groups in frequency dependent dynamic stiffness curves. Surprisingly, the PU curves were closest to the FREE sample curves. Those with load and direct contact with metal (MEW) became significantly stiffer, while restrained samples became softer. Significant differences (p<0.05, Mann-Whitney's U test) in cell vitality between samples from various groups could be seen in fluorescein diacetate (FDA) and propidium iodide (PI) stained samples by confocal microscopic analysis. The approximate mean percentages of living cells after 270 hours cultivation were: FREE 87%, MEW 3%, PUW 35%, and RESTR 66%. Test results indicate that it is possible to keep cartilage cells alive in cell culture incubator conditions for two weeks period under a 0.25 MPa unconfined static loading. The FREE samples were most successful and cells loaded with PU were more vital than cells loaded with metal.

    CONCLUSIONS: Based on the results, PU seems to be more compatible material than surgical steel in contact with living cartilage. Because of a large variation in the quality of bovine cartilage material from different animals, special care is necessary when selecting specimens to guarantee reliable and reproducible results.

  • 257.
    Qu, Chengjuan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Department of Orthopaedics, Traumatology and Hand Surgery, Kuopio University Hospital, Kuopio, Finland.
    Kaitainen, Salla
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Kröger, Heikki
    Department of Orthopaedics, Traumatology and Hand Surgery, Kuopio University Hospital, Kuopio, Finland.
    Lappalainen, Reijo
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Key Laboratory of Trace Elements and Endemic Diseases, National Health and Family Planning Commission, School of Public Health of Health Science Center, Xi’an Jiaotong University, Xi’an, China.
    Behavior of human bone marrow-derived mesenchymal stem cells on various titanium-based coatings2016In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 9, no 10, article id 827Article in journal (Refereed)
    Abstract [en]

    The chemical composition and texture of titanium coatings can influence the growth characteristics of the adhered cells. An enhanced proliferation of the human mesenchymal stem cells (hMSCs) would be beneficial. The present study was aimed to investigate whether titanium deposited at different atmospheres would affect the cell growth properties, cellular morphology, and expression of surface markers of hMSCs. Titanium-based coatings were deposited on silicon wafers under oxygen, nitrogen, or argon atmospheres by ultra-short pulsed laser deposition using two different gas pressures followed by heating at 400 °C for 2 h. The characteristics of the coated surfaces were determined via contact angle, zeta potential, and scanning electron microscopy (SEM) techniques. Human MSCs were cultivated on differently coated silicon wafers for 48 h. Subsequently, the cell proliferation rates were analyzed with an MTT assay. The phenotype of hMSCs was checked via immunocytochemical stainings of MSC-associated markers CD73, CD90, and CD105, and the adhesion, spreading, and morphology of hMSCs on coated materials via SEM. The cell proliferation rates of the hMSCs were similar on all coated silicon wafers. The hMSCs retained the MSC phenotype by expressing MSC-associated markers and fibroblast-like morphology with cellular projections. Furthermore, no significant differences could be found in the size of the cells when cultured on all various coated surfaces. In conclusion, despite certain differences in the contact angles and the zeta potentials of various titanium-based coatings, no single coating markedly improved the growth characteristics of hMSCs.

  • 258. Raina, Deepak Bushan
    et al.
    Larsson, David
    Umeå University, Faculty of Medicine, Department of Clinical Sciences. Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopedics, Lund, Sweden.
    Sezgin, Erdem Aras
    Isaksson, Hanna
    Tägil, Magnus
    Lidgren, Lars
    Biomodulation of an implant for enhanced bone-implant anchorage2019In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 96, p. 619-630Article in journal (Refereed)
    Abstract [en]

    Aseptic loosening of implants is the major cause for revision surgery. By modulating the bone-implant interface, early bone-implant anchorage could be improved. Implant surface manipulation by the addition of osteopromotive molecules locally and systemically to promote implant integration has been described with limited success. This study describes a novel approach by making the implant capable of biologically modulating its surroundings. It was hypothesized that the early implant fixation would improve by filling the interior of the implant with a carrier providing spatio-temporal release of bone active drugs with known osteogenic effect. The implant consisted of a threaded polyether ether ketone (PEEK) hollow chamber with holes at the bottom. The implant was filled with a calcium sulphate (CaS)/hydroxyapatite (HA) carrier, delivering two bone active molecules; zoledronic acid (ZA) and bone morphogenic protein-2 (BMP-2). At first, a rat abdominal muscle pouch model indicated a sustained in-vivo release of both I-125-rhBMP-2 (57%) and C-14-ZA (22%) from the CaS/HA carrier over a period of 4-weeks. The biomodulated implant was then inserted in the proximal tibia in rats with the following experimental groups: G1) Empty implant, G2) Implant + CaS/HA, G3) Implant + CaS/HA + ZA and G4) Implant + CaS/HA + ZA + rhBMP-2. Significantly higher bone volume (BV) was seen around the implant in groups G3 (3.3 +/- 0.7 mm(3)) and G4 (3.1 +/- 0.7 mm(3)) compared to the control (1.3 +/- 0.4 mm(3)) using micro-computed tomography and qualitative histology. Group G3, also exhibited significantly higher pull-out force and absorbed energy when compared to the control group G1. These findings indicate that a low dose of ZA alone, released in a controlled manner from within a fenestrated implant is enough to improve implant anchorage without the need of adding rhBMP-2. This simple method of using a fenestrated implant containing a ceramic carrier releasing bone active molecules improved bone anchorage and could clinically reduce prosthetic failure. Statement of Significance Aseptic loosening remains as a major cause for implant revisions and early reaction of surrounding bone to the prosthesis is important for longevity. A novel approach to enhance early bone-implant anchorage is presented. The implant is filled with a carrier providing controlled release of bone active molecules. In an animal model, a calcium sulphate (CaS)/hydroxyapatite (HA) carrier was used to provide a spatio-temporal release of bone morphogenic protein-2 (BMP-2) and zoledronic acid (ZA). Significantly better bone-implant integration was achieved using ZA alone, thereby eliminating the need for adding BMP-2. The developed method of implant biomodulation holds potential to prevent implant loosening and is an alternative to prosthetic coatings or systemic drug treatment. Importantly, all constituents are approved for clinical use.

  • 259. Raina, Deepak Bushan
    et al.
    Qayoom, Irfan
    Larsson, David
    Umeå University, Faculty of Medicine. Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopedics, Lund 22185, Sweden.
    Zheng, Ming Hao
    Kumar, Ashok
    Isaksson, Hanna
    Lidgren, Lars
    Tagil, Magnus
    Guided tissue engineering for healing of cancellous and cortical bone using a combination of biomaterial based scaffolding and local bone active molecule delivery2019In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 188, p. 38-49Article in journal (Refereed)
    Abstract [en]

    A metaphyseal bone defect due to infection, tumor or fracture leads to loss of cancellous and cortical bone. An animal model separating the cancellous and cortical healing was used with a combination of a macroporous gelatin-calcium sulphate-hydroxyapatite (Gel-CaS-HA) biomaterial as a cancellous defect filler, and a thin collagen membrane (CM) guiding cortical bone regeneration. The membrane was immobilized with bone morphogenic protein-2 (rhBMP-2) to enhance the osteoinductive properties. The Gel-CaS-HA cancellous defect filler contained both rhBMP-2 and a bisphosphonate, (zoledronate = ZA) to prevent premature callus resorption induced by the pro-osteoclast effect of rhBMP-2 alone. In the first part of the study, the CM delivering both rhBMP-2 and ZA was tested in a muscle pouch model in rats and the co-delivery of rhBMP-2 and ZA via the CM resulted in higher amounts of bone compared to rhBMP-2 alone. Secondly, an established tibia defect model in rats was used to study cortical and cancellous bone regeneration. The defect was left empty, filled with Gel-CaS-HA alone, Gel-CaS-HA immobilized with ZA or Gel-CaS-HA immobilized with rhBMP-2+ ZA. Functionalization of the Gel-CaS-HA scaffold with bioactive molecules produced significantly more bone in the cancellous defect and its surroundings but cortical defect healing was delayed likely due to the protrusion of the Gel-CaS-HA into the cortical bone. To guide cortical regeneration, the cortical defect was sealed endosteally by a CM with or without rhBMP-2. Subsequently, the cancellous defect was filled with Gel-CaS-HA containing ZA and rhBMP2 + ZA. In the groups where the CM was doped with rhBMP-2, significantly higher number of cortices bridged. The approach to guide cancellous as well as cortical bone regeneration separately in a metaphyseal defect using two bioactive molecule immobilized biomaterials is promising and could improve the clinical care of patients with metaphyseal defects.

  • 260.
    Rajendran, Vijayalakshmi
    et al.
    University of Aberdeen, Scotland.
    Netukova, Magdalena
    Charles University of Prague, Czech Republic.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. University of Montreal, Canada.
    Forrester, John V.
    University of Aberdeen, Scotland; University of Western Australia, Australia; Lions Eye Institute, Australia.
    Kuffova, Lucia
    University of Aberdeen, Scotland.
    Mesenchymal stem cell therapy for retro-corneal membrane - A clinical challenge in full-thickness transplantation of biosynthetic corneal equivalents2017In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 64, p. 346-356Article in journal (Refereed)
    Abstract [en]

    Artificial corneas (keratoprostheses) and biosynthetic collagen-based corneal equivalents are surgical implants designed to ease the global burden of corneal blindness. However, keratoprostheses in many cases fail due to development of fibrous retro-corneal membranes (RCM). Fibrous membranes which develop in the anterior chamber after prosthesis implantation do so on a matrix of fibrin. This study investigated fibrin deposition and RCM formation after full-thickness collagen-based hydrogel implants and compared them with syngeneic and allogeneic corneal grafts in mice. Fibrin cleared from the anterior chamber within 14 days in both allo- and syn-grafts but, persisted in hydrogel implants and developed into dense retro-corneal membrane (RCM) which were heavily infiltrated by activated myofibroblasts. In contrast, the number of CD11 b(+) macrophages infiltrating the initial deposition of fibrin in the anterior chamber (AC) after hydrogel implantation was markedly reduced compared to syn- and allo-grafts. Inoculation of mesenchymal stem cells prior to collagen gel implant promoted clearance of gel associated fibrin from the anterior chamber. We propose that a failure of macrophage-mediated clearance of fibrin may be the cause of RCM formation after collagen-based hydrogel implants and that mesenchymal stem cell therapy promotes clearance of fibrin and prevents RCM formation. Statement of Significance The manuscript addresses the potential value of bone marrow-derived mesenchymal stem cell therapy for retro-corneal membrane (RCM) formation in full-thickness transplantation of biosynthetic corneal equivalents. This work reports the pathophysiological changes in the anterior chamber of the mouse eye following full-thickness recombinant human cross-linked collagen-based hydrogel implants in which persistent fibrin promotes the development of dense RCM. Furthermore, pre-treatment with mesenchymal stem cells reduces RCM formation and enhances corneal transparency. (C) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  • 261.
    Ramachandraiah, Harisha
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Kugiejko, Karol
    KTH, School of Biotechnology (BIO).
    Pettersson, Torbjörn
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Heuchel, Rainer
    Karolinska Institutet.
    Löhr, Matthias
    karolinska Institute.
    Hedhammar, My
    KTH, School of Biotechnology (BIO), Protein Technology.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Microfluidic based circulating tumor cell isolation and release from whole blood of pancreatic cancer patients using bio-functionalized recombinant spider silkManuscript (preprint) (Other academic)
    Abstract [en]

    A bio-functionalized microsystem was developed for the capture and release of cancer cells from whole blood. Effective isolation and purification of circulating tumor cells from whole blood provides important capability for clinical application and biological research. Here, we demonstrate a single step surface modification procedure for a microfluidic device based on self-assembly of recombinant spider silk harbouring an affinity domain for antibody binding. The surfaces of microfluidic devices were conjugated/equipped with anti-EpCAM antibody for selective isolation of pancreatic cancer cells from spiked whole blood and finally circulating tumor cells from pancreatic cancer patients. Moreover, a protease-cleavage site in the recombinant spider silk proteins provides the unique option to release the captured cancer cells on command from the device without compromising the cell’s viability. Our approach offers a simple, easy and robust surface modification process with a 85% cancer cell capture efficiency. Subsequent addition of a site-specific protease results in the release of 95% of captured cells from the bio functionalized microfluidic systems. 

  • 262.
    Ramachandraiah, Harisha
    et al.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Pettersson, Torbjörn
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Russom, Aman
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Layer-by-layer system based cellulose nanofibrils for capture and release of cells in microfluidic deviceManuscript (preprint) (Other (popular science, discussion, etc.))
    Abstract [en]

    Selective isolation of cells, without inducing any phenotypic changes and maintaining cell viability will preserve the information necessary for down stream analysis. Here we present an ultra thin coating on the surface of disposable microfluidic device based on cellulose nanofibrils, that is modified to capture cells and for later release. Layer-by-layer technique facilitates the production of the thin coating of cellulose onto polymeric surfaces and modified to form affinity based cell capture surface. We demonstrate an  efficiently capture and release of cells, the release is done by selectively degrading 

  • 263.
    Ramstedt, Madeleine
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ribeiro, Isabel A. C.
    Bujdakova, Helena
    Mergulhão, Filipe J. M.
    Jordao, Luisa
    Thomsen, Peter
    Alm, Martin
    Burmølle, Mette
    Vladkova, Todorka
    Can, Fusun
    Reches, Meital
    Riool, Martijn
    Barros, Alexandre
    Reis, Rui L.
    Meaurio, Emilio
    Kikhney, Judith
    Moter, Annette
    Zaat, Sebastian A. J.
    Sjollema, Jelmer
    Evaluating Efficacy of Antimicrobial and Antifouling Materials for Urinary Tract Medical Devices: Challenges and Recommendations2019In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 19, no 5, article id 1800384Article, review/survey (Refereed)
    Abstract [en]

    In Europe, the mean incidence of urinary tract infections in intensive care units is 1.1 per 1000 patient‐days. Of these cases, catheter‐associated urinary tract infections (CAUTI) account for 98%. In total, CAUTI in hospitals is estimated to give additional health‐care costs of £1–2.5 billion in the United Kingdom alone. This is in sharp contrast to the low cost of urinary catheters and emphasizes the need for innovative products that reduce the incidence rate of CAUTI. Ureteral stents and other urinary‐tract devices suffer similar problems. Antimicrobial strategies are being developed, however, the evaluation of their efficacy is very challenging. This review aims to provide considerations and recommendations covering all relevant aspects of antimicrobial material testing, including surface characterization, biocompatibility, cytotoxicity, in vitro and in vivo tests, microbial strain selection, and hydrodynamic conditions, all in the perspective of complying to the complex pathology of device‐associated urinary tract infection. The recommendations should be on the basis of standard assays to be developed which would enable comparisons of results obtained in different research labs both in industry and in academia, as well as provide industry and academia with tools to assess the antimicrobial properties for urinary tract devices in a reliable way.

  • 264.
    Rashad, Ahmad
    et al.
    University of Bergen, Norway.
    Suliman, Salwa
    University of Bergen, Norway.
    Mustafa, Manal
    Oral Health Centre of Expertise in Western Norway, Norway.
    Pedersen, Torbjörn
    University of Bergen, Norway.
    Campodoni, Elisabetta
    National Research Council of Italy, Italy.
    Sandri, Monica
    National Research Council of Italy, Italy.
    Syverud, Kristin
    RISE - Research Institutes of Sweden, Bioeconomy, PFI. NTNU Norwegian University of Science and Technology, Norway.
    Mustafa, Kamal
    University of Bergen, Norway.
    Inflammatory responses and tissue reactions to wood-Based nanocellulose scaffolds2019In: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 97, p. 208-221Article in journal (Refereed)
    Abstract [en]

    Two wood-derived cellulose nanofibril (CNF) porous scaffolds were prepared by TEMPO-oxidation and carboxymethylation. The effects of these scaffolds on the production of inflammatory cytokines by human macrophage-like cells (U937) was profiled in vitro after 1 and 3 days and in subcutaneous tissues of rats after 4 and 30 days, using PCR and Multiplex arrays. Tissue culture plates (TCP) and gelatin scaffolds served as controls in vitro and in vivo respectively. After 3 days in vitro, there was no significant difference between the effects of CNF scaffolds and TCP on the production of chemokines/growth factors and pro-inflammatory cytokines. At day 4 in vivo there was significantly higher gene expression of the anti-inflammatory IL-1Ra in the CNF scaffolds than the gelatin scaffold. Production of IL-1β, IL-6, MCP-1, MIP-1α CXCL-1 and M-CSF was significantly less than in the gelatin, demonstrating an early mild inflammatory response. At day 30, both CNF scaffolds significantly stimulated the production of the anti-inflammatory cytokine IL-10. Unlike gelatin, neither CNF scaffold had degraded 180 days post-implantation. The slow degradation of CNF scaffolds resulted in a foreign body reaction, with high production of IL-1β, IL-2, TNF-α, IFN-ϒ, MCP-1, MIP-1α, M-CSF, VEGF cytokines and expression of MMP-9 gene. The surface chemistry of the CNF scaffolds elicited a modest effect on cytokine production and did not shift the inflammatory profile in vitro or in vivo. The decisive role in development of the foreign body reaction was the slow degradation of the CNF scaffolds.

  • 265.
    Rees, Adam
    et al.
    Swansea University, UK.
    Powell, Lydia C.
    Swansea University, UK; Cardiff University, UK.
    Chinga-Carrasco, Gary
    RISE, Innventia, PFI – Paper and Fiber Research Institute.
    Gethin, David T.
    Swansea University, UK.
    Syverud, Kristin
    RISE, Innventia, PFI – Paper and Fiber Research Institute.
    Hill, Katja E.
    Cardiff University, UK.
    Thomas, David W.
    Cardiff University, UK.
    3D bioprinting of carboxymethylated-periodate oxidized nanocellulose constructs for wound dressing applications2015In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, Vol. 2015, article id 925757Article in journal (Refereed)
    Abstract [en]

    Nanocellulose has a variety of advantages, which make the material most suitable for use in biomedical devices such as wound dressings. The material is strong, allows for production of transparent films, provides a moist wound healing environment, and can form elastic gels with bioresponsive characteristics. In this study, we explore the application of nanocellulose as a bioink for modifying film surfaces by a bioprinting process. Two different nanocelluloses were used, prepared with TEMPO mediated oxidation and a combination of carboxymethylation and periodate oxidation. The combination of carboxymethylation and periodate oxidation produced a homogeneous material with short nanofibrils, having widths <20 nm and lengths <200 nm. The small dimensions of the nanofibrils reduced the viscosity of the nanocellulose, thus yielding a material with good rheological properties for use as a bioink. The nanocellulose bioink was thus used for printing 3D porous structures, which is exemplified in this study. We also demonstrated that both nanocelluloses did not support bacterial growth, which is an interesting property of these novel materials.

  • 266.
    Richter, Maja
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    Study of immune and haemostatic response induced by protein multilayers.2010Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    FibMat2.0 is a fibrinogen multilayer developed by AddBIO. Other proteins such as immunoglobulin G (IgG) and human serum albumin (HSA) can also be used to build multilayers with the same technique. The aim of this study of FibMat2.0 was to investigate if the manufacturing of the protein multilayer would induce an immune or haemostatic response in the body. The multilayers of IgG and HSA were also studied. Methods such as null ellipsometry, imaging of coagulation and the cone-and-plate setup were used to study immune reactions, activation of the coagulation cascade, and stability of the multilayers.

    Small amounts of plasma proteins were adsorbed to fibrinogen multilayers, but complement proteins adsorbed only to the IgG matrix and high molecular weight kininogen (HMWK) adsorbed only to the HSA monolayer. The imaging of coagulation method indicated that the titanium surface and the HSA monolayer activate surface induced coagulation rapidly, whereas fibrinogen and IgG multilayers demonstrated longer coagulation times. Platelets and a few white blood cells were bound to titanium surfaces and fibrinogen multilayers, but not to IgG multilayers or HSA monolayers.

    A conclusion in this study is that the surface of an implant can be coated with FibMat2.0 without any risks, but more studies are needed to better understand the interactions between the surfaces prepared in the present study and the immune and the haemostatic systems of the human body.

  • 267.
    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. 

  • 268.
    Robo, Céline
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    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.
    Compressive fatigue properties of commercially available standard and low-modulus acrylic bone cements intended for vertebroplasty2018In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 82, p. 70-76Article in journal (Refereed)
    Abstract [en]

    Vertebroplasty (VP) is a minimally invasive surgical procedure commonly used to relieve severe back pain associated with vertebral compression fractures. The poly(methyl methacrylate) bone cement used during this procedure is however presumed to facilitate the occurrence of additional fractures next to the treated vertebrae. A reason for this is believed to be the difference in stiffness between the bone cement and the surrounding trabecular bone. The use of bone cements with lower mechanical properties could therefore reduce the risk of complications post-surgery. While intensive research has been performed on the quasi-static mechanical properties of these cements, there is no data on their long-term mechanical properties. In the present study, the in vitrocompressive fatigue performance as well as quasi-static mechanical properties of two commercially available acrylic bone cements - a low-modulus cement (Resilience®) and a standard cement (F20) from the same manufacturer - were determined. The quasi-static mechanical properties of the low-modulus and standard cements after 24h of setting were in the range of other vertebroplastic cements (σ=70-75 MPa; E=1600-1900 MPa). F20 displayed similar mechanical properties over time in 37˚C phosphate buffered saline solution, while the mechanical properties of the Resilience®cement decreased gradually due to an increased porosity in the polymeric matrix. The standard cement exhibited a fatigue limit of approx. 47 MPa, whereas the low-modulus cement showed a fatigue limit of approx. 31 MPa. 

    In summary, the low-modulus bone cement had a lower fatigue limit than the standard cement, as expected. However, this fatigue limit is still substantially higher than the stresses experienced by vertebral trabecular bone.  

  • 269.
    Rogstad Nordli, Henriette
    et al.
    NTNU Norwegian University of Science and Technology, Norway.
    Chinga-Carrasco, Gary
    RISE, Innventia, PFI – Paper and Fiber Research Institute.
    Rokstad, Anne Mari
    NTNU Norwegian University of Science and Technology, Norway.
    Pukstad, Brita
    NTNU Norwegian University of Science and Technology, Norway; Trondheim University Hospital, Norway.
    Producing ultrapure wood cellulose nanofibrils and evaluating the cytotoxicity using human skin cells2016In: Carbohydrate Polymers, ISSN 0144-8617, E-ISSN 1879-1344, Vol. 150, p. 65-73Article in journal (Refereed)
    Abstract [en]

    Wood cellulose nanofibrils (CNF) have been suggested as a potential wound healing material, but its utilization is limited by FDA requirements regarding endotoxin levels. In this study a method using sodium hydroxide followed by TEMPO mediated oxidation was developed to produce ultrapure cellulose nanofibrils, with an endotoxin level of 45 endotoxin units/g (EU/g) cellulose. Scanning transmission electron microscopy (S(T)EM) revealed a highly nanofibrillated structure (lateral width of 3.7 ± 1.3 nm). Assessment of cytotoxicity and metabolic activity on Normal Human Dermal Fibroblasts and Human Epidermal Keratinocytes was done. CNF-dispersion of 50 ÎŒg/ml did not affect the cells. CNF-aerogels induced a reduction of metabolic activity by the fibroblasts and keratinocytes, but no significant cell death. Cytokine profiling revealed no induction of the 27 cytokines tested upon exposure to CNF. The moisture-holding capacity of aerogels was relatively high (∌7500%), compared to a commercially available wound dressing (∌2500%), indicating that the CNF material is promising as dressing material for management of wounds with a moderate to high amount of exudate.

  • 270. Rossoll, Dennis
    et al.
    Bermudez, Rafael
    Hauss, Helena
    Schulz, Kai G.
    Riebesell, Ulf
    Sommer, Ulrich
    Winder, Monika
    Stockholm University, Faculty of Science, Department of Systems Ecology.
    Ocean acidification induced food quality deterioration constrains trophic transfer2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 4, p. e34737-Article in journal (Refereed)
    Abstract [en]

    Our present understanding of ocean acidification (OA) impacts on marine organisms caused by rapidly rising atmospheric carbon dioxide (CO2) concentration is almost entirely limited to single species responses. OA consequences for food web interactions are, however, still unknown. Indirect OA effects can be expected for consumers by changing the nutritional quality of their prey. We used a laboratory experiment to test potential OA effects on algal fatty acid (FA) composition and resulting copepod growth. We show that elevated CO2 significantly changed the FA concentration and composition of the diatom Thalassiosira pseudonana, which constrained growth and reproduction of the copepod Acartia tonsa. A significant decline in both total FAs (28.1 to 17.4 fg cell(-1)) and the ratio of long-chain polyunsaturated to saturated fatty acids (PUFA:SFA) of food algae cultured under elevated (750 mu atm) compared to present day (380 mu atm) pCO(2) was directly translated to copepods. The proportion of total essential FAs declined almost tenfold in copepods and the contribution of saturated fatty acids (SFAs) tripled at high CO2. This rapid and reversible CO2-dependent shift in FA concentration and composition caused a decrease in both copepod somatic growth and egg production from 34 to 5 eggs female(-1) day(-1). Because the diatom-copepod link supports some of the most productive ecosystems in the world, our study demonstrates that OA can have far-reaching consequences for ocean food webs by changing the nutritional quality of essential macromolecules in primary producers that cascade up the food web.

  • 271.
    Safdari, Majid
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Applied Physical Chemistry.
    Fischer, Andreas C.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Applied Physical Chemistry.
    Xu, Bo
    KTH, School of Chemical Science and Engineering (CHE), Centres, Centre of Molecular Devices, CMD. KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Kloo, Lars
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Applied Physical Chemistry.
    Gardner, James M.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Applied Physical Chemistry.
    Erratum to: Structure and function relationships in alkylammonium lead(II) iodide solar cells2015In: Journal of Materials Chemistry A, ISSN 2050-7488, Vol. 3, no 17, p. 9317-9317Article in journal (Refereed)
  • 272. Salvo, P.
    et al.
    Henry, O. Y. F.
    Dhaenens, K.
    Acero Sanchez, J. L.
    Gielen, A.
    Werne Solnestam, Beata
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    O'Sullivan, C. K.
    Vanfleteren, J.
    Fabrication and functionalization of PCB gold electrodes suitable for DNA-based electrochemical sensing2014In: Bio-medical materials and engineering, ISSN 0959-2989, E-ISSN 1878-3619, Vol. 24, no 4, p. 1705-1714Article in journal (Refereed)
    Abstract [en]

    The request of high specificity and selectivity sensors suitable for mass production is a constant demand in medical research. For applications in point-of-care diagnostics and therapy, there is a high demand for low cost and rapid sensing platforms. This paper describes the fabrication and functionalization of gold electrodes arrays for the detection of deoxyribonucleic acid (DNA) in printed circuit board (PCB) technology. The process can be implemented to produce efficiently a large number of biosensors. We report an electrolytic plating procedure to fabricate low-density gold microarrays on PCB suitable for electrochemical DNA detection in research fields such as cancer diagnostics or pharmacogenetics, where biosensors are usually targeted to detect a small number of genes. PCB technology allows producing high precision, fast and low cost microelectrodes. The surface of the microarray is functionalized with self-assembled monolayers of mercaptoundodecanoic acid or thiolated DNA. The PCB microarray is tested by cyclic voltammetry in presence of 5 mM of the redox probe K3Fe(CN6) in 0.1 M KCl. The voltammograms prove the correct immobilization of both the alkanethiol systems. The sensor is tested for detecting relevant markers for breast cancer. Results for 5 nM of the target TACSTD1 against the complementary TACSTD1 and non-complementary GRP, MYC, SCGB2A1, SCGB2A2, TOP2A probes show a remarkable detection limit of 0.05 nM and a high specificity.

  • 273.
    Samarawickrama, Chameen
    et al.
    Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, London, England;UCL Inst Ophthalmol, London, England;Univ Sydney, Discipline Clin Ophthalmol & Eye Hlth, Sydney, NSW, Australia.
    Samanta, Ayan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. LV Prasad Eye Inst, Tej Kohli Cornea Inst, Hyderabad, Telangana, India.
    Liszka, Aneta
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Fagerholm, Per
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
    Buznyk, Oleksiy
    Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden;NAMS Ukraine, Filatov Inst Eye Dis & Tissue Therapy, Dept Reconstruct Microsurg Burn Pathol, Odessa, Ukraine.
    Griffith, May
    LV Prasad Eye Inst, Tej Kohli Cornea Inst, Hyderabad, Telangana, India;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden;Univ Montreal, Maisonneuve Rosemont Hosp, Res Ctr, Montreal, PQ, Canada;Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada.
    Allan, Bruce
    Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Res Ctr, London, England;UCL Inst Ophthalmol, London, England.
    Collagen-Based Fillers as Alternatives to Cyanoacrylate Glue for the Sealing of Large Corneal Perforations2018In: Cornea, ISSN 0277-3740, E-ISSN 1536-4798, Vol. 37, no 5, p. 609-616Article in journal (Refereed)
    Abstract [en]

    Purpose: To describe the use of collagen-based alternatives to cyanoacrylate glue for the sealing of acute corneal perforations. Methods: A collagen analog comprising a collagen-like peptide conjugated to polyethylene glycol (CLP-PEG) and its chemical crosslinker were tested for biocompatibility. These CLP-PEG hydrogels, which are designed to act as a framework for corneal tissue regeneration, were then tested as potential fillers in ex vivo human corneas with surgically created full-thickness perforations. Bursting pressures were measured in each of 3 methods (n = 10 for each condition) of applying a seal: 1) cyanoacrylate glue with a polyethylene patch applied ab externo (gold standard); 2) a 100-mu m thick collagen hydrogel patch applied ab interno, and 3) the same collagen hydrogel patch applied ab interno supplemented with CLP-PEG hydrogel molded in situ to fill the remaining corneal stromal defect. Results: Cyanoacrylate gluing achieved a mean bursting pressure of 325.9 mm Hg, significantly higher than the ab interno patch alone (46.3 mm Hg) and the ab interno patch with the CLP-PEG filler (86.6 mm Hg). All experimental perforations were sealed effectively using 100 mu m hydrogel sheets as an ab interno patch, whereas conventional ab externo patching with cyanoacrylate glue failed to provide a seal in 30% (3/10) cases. Conclusions: An ab interno patch system using CLP-PEG hydrogels designed to promote corneal tissue regeneration may be a viable alternative to conventional cyanoacrylate glue patching for the treatment of corneal perforation. Further experimentation and material refinement is required in advance of clinical trials.

  • 274.
    Sandberg, Olof
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Aspenberg, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Glucocorticoids inhibit shaft fracture healing but not metaphyseal bone regeneration under stable mechanical conditions2015In: BONE and JOINT RESEARCH, ISSN 2046-3758, Vol. 4, no 10, p. 170-175Article in journal (Refereed)
    Abstract [en]

    Objectives Healing in cancellous metaphyseal bone might be different from midshaft fracture healing due to different access to mesenchymal stem cells, and because metaphyseal bone often heals without a cartilaginous phase. Inflammation plays an important role in the healing of a shaft fracture, but if metaphyseal injury is different, it is important to clarify if the role of inflammation is also different. The biology of fracture healing is also influenced by the degree of mechanical stability. It is unclear if inflammation interacts with stability-related factors.

    Methods We investigated the role of inflammation in three different models: a metaphyseal screw pull-out, a shaft fracture with unstable nailing (IM-nail) and a stable external fixation (ExFix) model. For each, half of the animals received dexamethasone to reduce inflammation, and half received control injections. Mechanical and morphometric evaluation was used.

    Results As expected, dexamethasone had a strong inhibitory effect on the healing of unstable, but also stable, shaft fractures. In contrast, dexamethasone tended to increase the mechanical strength of metaphyseal bone regenerated under stable conditions.

    Conclusions It seems that dexamethasone has different effects on metaphyseal and diaphyseal bone healing. This could be explained by the different role of inflammation at different sites of injury.

  • 275.
    Sarve, Hamid
    et al.
    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.
    Friberg, Bertil
    Brånemark Clinic.
    Borgefors, Gunilla
    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.
    Johansson, Carina B.
    University of Gothenburg, Department of Prosthodontics/Dental Materials Science, Institute of Odontology.
    Introducing a novel analysis technique for osseointegrated dental implants retrieved 29 years postsurgery2013In: Clinical Implant Dentistry and Related Research, ISSN 1523-0899, E-ISSN 1708-8208, Vol. 15, no 4, p. 538-549Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate osseointegration of oral implants, which were retrieved from a patient after 29 years in situ, we use novel three-dimensional analysis methods and visualization techniques that supplement conventional two-dimensional analysis. Materials and Methods: The sample processing involved nondecalcification and embedment in resin. Conventional two-dimensional histomorphometrical methods were conducted. Additionally, the quantification was extended to three-dimensional by using synchrotron radiation micro-computed tomography (SRmCT) technique and two relevant visualization methods for the three-dimensional data were introduced. Results: The three-dimensional results involved three-dimensional quantification and visualization of two implant samples with methods beyond state-of-the-art. Traditional two-dimensional histomorphometrical results revealed a mean bone-implant contact (BIC) of about 50%. In most samples, bone area (BA) was lower inside the treads compared with out-folded mirror images, which were confirmed by the three-dimensional quantification. The BIC along four selected regions showed highest percentages in the bottom/valley region and lowest in the thread-peak region. Qualitative observations revealed ongoing bone remodeling areas in all samples. The apical hole demonstrated high osseointegration. Conclusion: The novel techniques including an animation and an out-folding of BIC and BA enabled a simultaneous visualization of the three-dimensional material obtained from SRmCT data. However, the two-dimensional histological sections were needed for qualitative and quantitative evaluation of osseointegration and, thus, both methods are considered equally important.

  • 276. Schizas, Nikos
    et al.
    Rojas, Ramiro
    Kootala, Sujit
    Andersson, Brittmarie
    Pettersson, Jennie
    Hilborn, Jons
    Hailer, Nils P
    Hyaluronic acid-based hydrogel enhances neuronal survival in spinal cord slice cultures from postnatal mice2013In: Journal of biomaterials applications, ISSN 0885-3282, E-ISSN 1530-8022, Vol. 28, no 6, p. 825-836Article in journal (Refereed)
    Abstract [en]

    Numerous biomaterials based on extracellular matrix-components have been developed. It was our aim to investigate whether a hyaluronic acid-based hydrogel improves neuronal survival and tissue preservation in organotypic spinal cord slice cultures. Organotypic spinal cord slice cultures were cultured for 4 days in vitro (div), either on hyaluronic acid-based hydrogel (hyaluronic acid-gel group), collagen gel (collagen group), directly on polyethylene terephthalate membrane inserts (control group), or in the presence of soluble hyaluronic acid (soluble hyaluronic acid group). Cultures were immunohistochemically stained against neuronal antigen NeuN and analyzed by confocal laser scanning microscopy. Histochemistry for choline acetyltransferance, glial fibrillary acidic protein, and Griffonia simplicifolia isolectin B4 followed by quantitative analysis was performed to assess motorneurons and different glial populations. Confocal microscopic analysis showed a 4-fold increase in the number of NeuN-positive neurons in the hyaluronic acid-gel group compared to both collagen (p < 0.001) and control groups (p < 0.001). Compared to controls, organotypic spinal cord slice cultures maintained on hyaluronic acid-based hydrogel showed 5.9-fold increased survival of choline acetyltransferance-positive motorneurons (p = 0.008), 2-fold more numerous resting microglial cells in the white matter (p = 0.031), and a 61.4% reduction in the number of activated microglial cells within the grey matter (p = 0.05). Hyaluronic acid-based hydrogel had a shear modulus (G′) of ≈1200 Pascals (Pa), which was considerably higher than the ≈25 Pa measured for collagen gel. Soluble hyaluronic acid failed to improve tissue preservation. In conclusion, hyaluronic acid-based hydrogel improves neuronal and - most notably - motorneuron survival in organotypic spinal cord slice cultures and microglial activation is limited. The positive effects of hyaluronic acid-based hydrogel may at least in part be due to its mechanical properties.

  • 277.
    Segerholm, Kristoffer
    KTH, School of Architecture and the Built Environment (ABE), Civil and Architectural Engineering.
    Wood Plastic Composites made from Modified Wood: Aspects on Moisture Sorption, Micromorphology and Durability2007Licentiate thesis, comprehensive summary (Other scientific)
    Abstract [en]

    Wood plastic composite (WPC) materials have seen a continuous market growth worldwide in the last decade. So-called extruded WPC profiles are today mainly used in outdoor applications, e.g. decking, railing and fencing. In outdoor conditions, moisture sorption in the wood component combined with temperature induced movements of the polymer matrix causes deformations of such composites. On the macroscopic scale this may lead to unacceptable warp, cup and bow of the WPC products, but on a microscopic scale, the movements will cause interfacial cracks between the particles and the matrix, resulting in little or no ability to transfer and re-distribute loads throughout the material. Moisture within the composite will also allow fungi and micro organisms to attack the wood particles.

    The conceptual idea of this work is to use a chemically modified wood component in WPCs to enhance their long term performance. These chemically modified wood particles exhibit reduced susceptibility to moisture, resulting in better dimensional stability and a higher resistance to biological degradation as compared to that of unmodified wood. The objective of this thesis is to study the effects of using modified wood in WPCs on their moisture sorption behaviour, micromorphology and microbiological durability. The modification methods used were acetylation, heat treatment and furfurylation.

    Equilibrium moisture content (EMC) and sorption behaviour of WPCs were determined by water vapour sorption experiments. The use of thin sections of the composites enabled EMC to be reached within a comparably short time span. The micromorphology was studied by LV-SEM (low vacuum-scanning electron microscope) using a specially designed sample preparation technique based on UV laser. The biological durability was evaluated by laboratory fungal test methods.

    The moisture sorption experiments showed lower moisture levels for all the composites when modified wood particles were used. This was also reflected in the micromorphological studies where pronounced wood-plastic interfacial cracks were formed due to moisture movement in the composites with unmodified wood particles. The sample preparation technique by UV laser proved to be a powerful tool for preparing surfaces for micromorphological studies without adding mechanical defects caused by the sample preparation technique itself. Results from the durability test showed that WPCs with modified wood particles are highly resistant to decay by fungi.

  • 278.
    Selegård, Robert
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Aronsson, Christopher
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Brommesson, Caroline
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
    Dånmark, Staffan
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Aili, Daniel
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Folding driven self-assembly of a stimuli-responsive peptide-hyaluronan hybrid hydrogel2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 7013Article in journal (Refereed)
    Abstract [en]

    Protein-metal ion interactions are ubiquitous in nature and can be utilized for controlling the self-assembly of complex supramolecular architectures and materials. Here, a tunable supramolecular hydrogel is described, obtained by self-assembly of a Zn2+-responsive peptide-hyaluronic acid hybrid synthesized using strain promoted click chemistry. Addition of Zn2+ triggers folding of the peptides into a helix-loop-helix motif and dimerization into four-helix bundles, resulting in hydrogelation. Removal of the Zn2+ by chelators results in rapid hydrogel disassembly. Degradation of the hydrogels can also be time-programed by encapsulation of a hydrolyzing enzyme within the gel, offering multiple possibilities for modulating materials properties and release of encapsulated species. The hydrogel further shows potential antioxidant properties when evaluated using an in vitro model for reactive oxygen species.

  • 279.
    Shah, Furqan A.
    et al.
    University of Gothenburg, Sweden.
    Omar, Omar
    University of Gothenburg, Sweden.
    Suska, Felicia
    University of Gothenburg, Sweden.
    Snis, Anders
    University of Gothenburg, Sweden; Arcam AB, Sweden.
    Matic, Aleksandar
    Chalmers University of Technology, Sweden.
    Emanuelsson, Lena
    University of Gothenburg, Sweden.
    Norlindh, Birgitta
    University of Gothenburg, Sweden.
    Lausmaa, Jukka
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik. University of Gothenburg, Sweden.
    Thomsen, Peter
    University of Gothenburg, Sweden.
    Palmquist, Anders
    University of Gothenburg, Sweden.
    Long-term osseointegration of 3D printed CoCr constructs with an interconnected open-pore architecture prepared by electron beam melting2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 36, p. 296-309Article in journal (Refereed)
    Abstract [en]

    In orthopaedic surgery, cobalt chromium (CoCr) based alloys are used extensively for their high strength and wear properties, but with concerns over stress shielding and bone resorption due to the high stiffness of CoCr. The structural stiffness, principally related to the bulk and the elastic modulus of the material, may be lowered by appropriate design modifications, to reduce the stiffness mismatch between metal/alloy implants and the adjacent bone. Here, 3D printed CoCr and Ti6Al4V implants of similar macro-geometry and interconnected open-pore architecture prepared by electron beam melting (EBM) were evaluated following 26 week implantation in adult sheep femora. Despite higher total bone-implant contact for Ti6Al4V (39 ± 4%) than CoCr (27 ± 4%), bone formation patterns were similar, e.g., densification around the implant, and gradual ingrowth into the porous network, with more bone in the outer half (periphery) than the inner half (centre). Raman spectroscopy revealed no major differences in mineral crystallinity, the apatite-to-collagen ratio, or the carbonate-to-phosphate ratio. Energy dispersive X-ray spectroscopy showed similar Ca/P ratio of the interfacial tissue adjacent to both materials. Osteocytes made direct contact with CoCr and Ti6Al4V. While osteocyte density and distribution in the new-formed bone were largely similar for the two alloys, higher osteocyte density was observed at the periphery of the porous network for CoCr, attributable to slower remodelling and a different biomechanical environment. The results demonstrate the possibility to achieve bone ingrowth into open-pore CoCr constructs, and attest to the potential for fabricating customised osseointegrated CoCr implants for load-bearing applications. Statement of Significance Although cobalt chromium (CoCr) based alloys are used extensively in orthopaedic surgery, stress shielding due to the high stiffness of CoCr is of concern. To reduce the stiffness mismatch between CoCr and bone, CoCr and Ti6Al4V implants having an interconnected open-pore architecture were prepared by electron beam melting (EBM). After six months of submerged healing in sheep, both alloys showed similar patterns of bone formation, with densification around the implant and gradual ingrowth into the porous network. The molecular and elemental composition of the interfacial tissue was similar for both alloys. Osteocytes made direct contact with both alloys, with similar overall osteocyte density and distribution. The work attests to the potential for achieving osseointegration of EBM manufactured porous CoCr implants.

  • 280.
    Shah, Furqan A.
    et al.
    University of Gothenburg, Sweden; BIOMATCELL VINN Excellence Centre of Biomaterials and Cell Therapy, Sweden.
    Stenlund, Patrik
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Kemi Material och Ytor, Medicinteknik. University of Gothenburg, Sweden; BIOMATCELL VINN Excellence Centre of Biomaterials and Cell Therapy, Sweden.
    Martinelli, Anna
    Chalmers University of Technology, Sweden.
    Thomsen, Peter
    University of Gothenburg, Sweden; BIOMATCELL VINN Excellence Centre of Biomaterials and Cell Therapy, Sweden.
    Palmquist, Anders
    University of Gothenburg, Sweden; BIOMATCELL VINN Excellence Centre of Biomaterials and Cell Therapy, Sweden.
    Direct communication between osteocytes and acid-etched titanium implants with a sub-micron topography2016In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 27, no 11, article id 167Article in journal (Refereed)
    Abstract [en]

    The osteocyte network, through the numerous dendritic processes of osteocytes, is responsible for sensing mechanical loading and orchestrates adaptive bone remodelling by communicating with both the osteoclasts and the osteoblasts. The osteocyte network in the vicinity of implant surfaces provides insight into the bone healing process around metallic implants. Here, we investigate whether osteocytes are able to make an intimate contact with topologically modified, but micrometre smooth (Sa &lt; 0.5 µm) implant surfaces, and if sub-micron topography alters the composition of the interfacial tissue. Screw shaped, commercially pure (cp-Ti) titanium implants with (i) machined (Sa = ~0.2 µm), and (ii) two-step acid-etched (HF/HNO3 and H2SO4/HCl; Sa = ~0.5 µm) surfaces were inserted in Sprague Dawley rat tibia and followed for 28 days. Both surfaces showed similar bone area, while the bone-implant contact was 73 % higher for the acid-etched surface. By resin cast etching, osteocytes were observed to maintain a direct intimate contact with the acid-etched surface. Although well mineralised, the interfacial tissue showed lower Ca/P and apatite-to-collagen ratios at the acid-etched surface, while mineral crystallinity and the carbonate-to-phosphate ratios were comparable for both implant surfaces. The interfacial tissue composition may therefore vary with changes in implant surface topography, independently of the amount of bone formed. Implant surfaces that influence bone to have higher amounts of organic matrix without affecting the crystallinity or the carbonate content of the mineral phase presumably result in a more resilient interfacial tissue, better able to resist crack development during functional loading than densely mineralised bone.

  • 281.
    Shah, Furqan A.
    et al.
    Univ Gothenburg, Sweden; BIOMATCELL VINN Excellence Ctr Biomat and Cell Ther, Sweden.
    Stoica, Adrian
    Masaryk Univ, Czech Republic.
    Cardemil, Carina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Maxillofacial Unit. Univ Gothenburg, Sweden; BIOMATCELL VINN Excellence Ctr Biomat and Cell Ther, Sweden.
    Palmquist, Anders
    Univ Gothenburg, Sweden; BIOMATCELL VINN Excellence Ctr Biomat and Cell Ther, Sweden.
    Multiscale characterization of cortical bone composition, microstructure, and nanomechanical properties in experimentally induced osteoporosis2018In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, Vol. 106, no 4, p. 997-1007Article in journal (Refereed)
    Abstract [en]

    Cortical bone plays a vital role in determining overall bone strength. We investigate the structural, compositional, and nanomechanical properties of cortical bone following ovariectomy (OVX) of 12-week-old Sprague Dawley rats, since this animal model is frequently employed to evaluate the performance of implantable biomaterials in compromised bone healing conditions. Morphological parameters and material properties of bone in the geometrical center of the femoral cortex were investigated four and eight weeks post-OVX and in unoperated controls (Ctrl), using X-ray micro-computed tomography, backscattered electron scanning electron microscopy, Raman spectroscopy, and nanoindentation. The OVX animals showed increase in body weight, diminished bone mineral density, increased intracortical porosity, but increased bone mass through periosteal apposition (e.g., increases in periosteal perimeter, cortical cross-sectional thickness, and cross-sectional area). However, osteocyte densities, osteocyte lacunar dimensions, and the nanomechanical behavior on the single mineralized collagen fibril level remained unaffected. Our correlative multiscale investigation provides structural, chemical, and nanomechanical evidence substantiating earlier reports suggesting that rats ovariectomized at 12 weeks undergo simultaneous bone loss and growth, resulting in the effects of OVX being less obvious. Periosteal apposition contradicts the conventional view of bone loss in osteoporosis but appears advantageous for the greater functional demand imposed on the skeleton by increased body weight and fragility induced by increased intracortical porosity. Through a variety of morphological changes, it is likely that 12-week-old rats are able to adapt to OVX-related microstructural and compositional alterations. (c) 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 997-1007, 2018.

  • 282.
    Shah, Furqan
    et al.
    Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Department of Materials Science and Engineering, McMaster University, Hamilton .
    Lee, Bryan
    School of Biomedical Engineering, McMaster University, Hamilton.
    Tedesco, James
    Department of Materials Science and Engineering, McMaster University, Hamilton.
    Larsson Wexell, Cecilia
    Department of Biomaterials, Sahlgrenska Academy at University, Department of Oral and Maxillofacial Surgery, Sö dra Älvsborg Hospital of Gothenburg, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therap.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Thomsen, Peter
    Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg,BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy .
    Grandfield, Kathryn
    School of Biomedical Engineering, McMaster University, Hamilton, Department of Materials Science and Engineering, McMaster University, Hamilton.
    Palmquist, Anders
    Department of Biomaterials, Sahlgrenska Academy at University of Gothenburg, BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy .
    Micrometre-sized magnesium whitlockite crystals in micropetrosis of bisphosphonate-exposed human alveolar bone2017In: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 17, no 10, p. 6210-6216Article in journal (Refereed)
    Abstract [en]

    Osteocytes are contained within spaces called lacunae and play a central role in bone remodelling. Administered frequently to prevent osteoporotic fractures, antiresorptive agents such as bisphosphonates suppress osteocyte apoptosis and may be localized within osteocyte lacunae. Bisphosphonates also reduce osteoclast viability and thereby hinder the repair of damaged tissue. Osteocyte lacunae contribute to toughening mechanisms. Following osteocyte apoptosis, the lacunar space undergoes mineralization, termed “micropetrosis”. Hypermineralized lacunae are believed to increase bone fragility. Using nanoanalytical electron microscopy with complementary spectroscopic and crystallographic experiments, postapoptotic mineralization of osteocyte lacunae in bisphosphonate-exposed human bone was investigated. We report an unprecedented presence of ∼80 nm to ∼3 μm wide, distinctly faceted, magnesium whitlockite [Ca18Mg2(HPO4)2(PO4)12] crystals and consequently altered local nanomechanical properties. These findings have broad implications on the role of therapeutic agents in driving biomineralization and shed new insights into a possible relationship between bisphosphonate exposure, availability of intracellular magnesium, and pathological calcification inside lacunae.

  • 283.
    Shi, Liyang
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Han, Yuanyuan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Ossipov, Dmitri
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    “Smart” drug loaded nanoparticle delivery from a self-healing hydrogel enabled by dynamic magnesium–biopolymer chemistry2016In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 52, no 74, p. 11151-11154Article in journal (Refereed)
    Abstract [en]

    We report a strategy to generate a self-healing and pH responsive hydrogel network between drug-loaded nanoparticles and natural polysaccharides via magnesium–bisphosphonate ligand interactions. The injectable drug depot disassembles in a tumor-specific environment, providing localized uptake of the nanoparticles, which is highly appreciated in drug delivery applications and manufacturing of drug-loaded biomaterials using a syringe-based deposition technique.

  • 284.
    Shi, Liyang
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Ossipov, Dmitri
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Injectable hydrogel consisting of bisphosphonate-functionalized hyaluronan and doxorubicin@magnesium silicate nanoparticles for anti-cancer therapy2016Conference paper (Refereed)
  • 285.
    Shrestha, Neha
    et al.
    Catholic University of Louvain, Belgium.
    Bouttefeux, Oriane
    Catholic University of Louvain, Belgium.
    Vanvarenberg, Kevin
    Catholic University of Louvain, Belgium.
    Lundquist, Patrik
    Uppsala University, Sweden.
    Cunarro, Juan
    University of Santiago de Compostela, Spain.
    Tovar, Sulay
    University of Santiago de Compostela, Spain.
    Khodus, Georgiy
    Uppsala University, Sweden.
    Andersson, Ellen
    Vrinnevi Hospital, Sweden.
    Keita, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Gonzalez Dieguez, Carlos
    University of Santiago de Compostela, Spain.
    Artursson, Per
    Uppsala University, Sweden.
    Preat, Veronique
    Catholic University of Louvain, Belgium.
    Beloqui, Ana
    Catholic University of Louvain, Belgium.
    The stimulation of GLP-1 secretion and delivery of GLP-1 agonists &ITvia&IT nanostructured lipid carriers2018In: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 10, no 2, p. 603-613Article in journal (Refereed)
    Abstract [en]

    Nanoparticulate based drug delivery systems have been extensively studied to efficiently encapsulate and deliver peptides orally. However, most of the existing data mainly focus on the nanoparticles as a drug carrier, but the ability of nanoparticles having a biological effect has not been exploited. Herein, we hypothesize that nanostructured lipid carriers (NLCs) could activate the endogenous glucagon-like peptide-1 (GLP-1) secretion and also act as oral delivery systems for GLP-1 analogs (exenatide and liraglutide). NLCs effectively encapsulated the peptides, the majority of which were only released under the intestinal conditions. NLCs, with and without peptide encapsulation, showed effective induction of GLP-1 secretion in vitro from the enteroendocrinal L-cells (GLUTag). NLCs also showed a 2.9-fold increase in the permeability of exenatide across the intestinal cell monolayer. The intestinal administration of the exenatide and liraglutide loaded NLCs did not demonstrate any glucose lowering effect on normal mice. Further, ex vivo studies depicted that the NLCs mainly adhered to the mucus layer. In conclusion, this study demonstrates that NLCs need further optimization to overcome the mucosal barrier in the intestine; nonetheless, this study also presents a promising strategy to use a dual-action drug delivery nanosystem which synergizes its own biological effect and that of the encapsulated drug molecule.

  • 286.
    Simpson-Edin, J. G.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Scalet, N.
    Linköping Univ, IFM, Linkoping, Ostergotland, Sweden..
    Griffith, M.
    Univ Montreal, Opthalmol, Montreal, PQ, Canada..
    Combining Electrospinning And 3D Printing For A New Generation Of Nerve Guides2018In: Cytotherapy, ISSN 1465-3249, E-ISSN 1477-2566, Vol. 20, no 5, p. S15-S15Article in journal (Refereed)
  • 287.
    Sjögren, Göran
    et al.
    Umeå University, Faculty of Medicine, Odontology, Dental Materials Science.
    Lantto, Rolf
    Granberg, Åsa
    Sundström, Bengt-Olov
    Tillberg, Anders
    Umeå University, Faculty of Medicine, Odontology, Dental Materials Science.
    Clinical examination of leucite-reinforced glass-ceramic crowns (Empress) in general practice: a retrospective study1999In: International Journal of Prosthodontics, ISSN 0893-2174, E-ISSN 1139-9791, Vol. 12, no 2, p. 122-128Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The purpose of this study was to retrospectively evaluate leucite reinforced-glass ceramic crowns (Empress) placed in patients who regularly visit general practices. MATERIALS AND METHODS: One hundred ten Empress crowns, placed in 29 patients who visited a general practice on a regular basis, were evaluated according to the California Dental Association's (CDA) quality evaluation system. In addition, the occurrence of plaque and certain gingival conditions was evaluated. All crowns were luted with resin composite cement. The mean and median years in function for the crowns were 3.6 and 3.9 years, respectively. RESULTS: Based on the CDA criteria, 92% of the 110 crowns were rated "satisfactory." Eighty-six percent were given the CDA rating "excellent" for margin integrity. Fracture was registered in 6% of the 110 crowns. Of the remaining 103 crowns, the CDA rating excellent was given to 74% for anatomic form, 86% for color, and 90% for surface. No significant differences (P > 0.05) were observed regarding fracture rates between anterior and posterior crowns. With regard to the occurrence of plaque and bleeding on probing, no significant differences (P > 0.05) were observed between the Empress crowns and the controls. CONCLUSION: Most of the fractured crowns had been placed on molars or premolars. Although the difference between anterior and posterior teeth was not statistically significant with respect to the fracture rates obtained, the number of fractured crowns placed on posterior teeth exceeded that of those placed on anterior teeth. The difference between the fracture rates may have clinical significance, and the risk of fracture has to be taken into consideration when placing crowns on teeth that are likely to be subjected to high stress levels.

  • 288.
    Sjögren, Göran
    et al.
    Umeå University, Faculty of Medicine, Odontology, Dental Materials Science.
    Lantto, Rolf
    Tillberg, Anders
    Umeå University, Faculty of Medicine, Odontology, Dental Materials Science.
    Clinical evaluation of all-ceramic crowns (Dicor) in general practice.1999In: The Journal of prosthetic dentistry (Print), ISSN 0022-3913, E-ISSN 1097-6841, Vol. 81, no 3, p. 277-284Article in journal (Refereed)
    Abstract [en]

    STATEMENT OF PROBLEM: There are few studies regarding all-ceramic full crowns placed by general practitioners; however, most dental restorations are carried out by general practitioners, and their clinical performance may be of particular interest. PURPOSE: Ninety-eight all-ceramic Dicor crowns placed in 46 patients regularly visiting a general practice were evaluated with the California Dental Association's (CDA) criteria. Mean and median ages of the crowns were 6.1 and 5.8 years, respectively (range 1.4 to 10. 9 years). Crowns were luted with either a glass ionomer, zinc phosphate, or resin composite cement. RESULTS. Of the 98 crowns, 82% were rated satisfactory. For marginal integrity, 51% were rated excellent. Fracture was registered in 14 all crowns, and 1 endodontically treated tooth with a Dicor crown was extracted because of root fracture; of the remaining 83 crowns, 55% were rated excellent for color. Corresponding figures for surface and anatomic form were 46% and 23%, respectively. The most common finding was slightly rough surfaces (64%). No statistically significant difference was observed for fracture rates obtained when the crowns luted with different luting agents were compared (P >.05). There was no more plaque or bleeding on probing (P >.05) in connection with the Dicor crowns than in the control surfaces.

  • 289.
    Sjögren, Göran
    et al.
    Umeå University, Faculty of Medicine, Odontology, Dental Materials Science.
    Sletten, Gaynour
    Scandinaivian Institute of Dental Materials, Haslum, Norway.
    Dahl, Jon E
    Scandinaivian Institute of Dental Materials, Haslum, Norway.
    Cytotoxicity of dental alloys, metals, and ceramics assessed by millipore filter, agar overlay, and MTT tests.2002In: The Journal of Prosthetic Dentistry, ISSN 0022-3913, Vol. 84, no 2, p. 229-236Article in journal (Refereed)
    Abstract [en]

    Statement of Problem: Biocompatibility of dental materials is dependent on the release of elements from the materials. In addition, the composition, pretreatment, and handling of the materials influence the element release. Purpose: This study evaluated the cytotoxicity of dental alloys, metals, and ceramics, with specific emphasis on the effects of altering the composition and the pretreatment. Material and Methods: By using cells from a mouse fibroblast cell line and the agar overlay test, Millipore filter test, and MTT test, cytotoxicity of various metals, metal alloys, and ceramics for dental restoration were studied. Effects of altering the composition of a high noble gold alloy and of pretreatment of a ceramic-bonding alloy were also studied. In addition, the release of elements into the cell culture medium by the materials studied was measured using an inductively coupled plasma optical emission spectrophotometer. The results of the MTT test were analyzed statistically using ANOVA and Scheffé test at a significance level of P<.05. Results: Specimens manufactured from materials intended for dental restorations and handled in accordance with the manufacturers’ instructions were ranked from “noncytotoxic” to “mildly cytotoxic” according to the agar overlay and Millipore filter tests. For the MTT test, no significant differences were observed between these materials and controls, with the exception of JS C-gold and unalloyed titanium. The modified materials were ranked from “mildly cytotoxic” to “moderately cytotoxic” in the agar overlay and Millipore filter tests and from “noncytotoxic” to “moderately cytotoxic” in the MTT test. Thus, cytotoxicity was related to the alloy composition and treatment. The release of Cu and Zn seemed to be important for the cytotoxic effect. Conclusion: Alterations in the composition and the pretreatment can greatly influence the cytotoxicity, and the results stress the importance of carefully following the manufacturers’ instructions when handling dental materials.

  • 290. Skedung, Lisa
    et al.
    Arvidsson, Martin
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Chung, Jun Young
    Stafford, Christopher M.
    Berglund, Birgitta
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Karolinska Institutet, Sweden.
    Rutland, Mark W.
    Feeling Small: Exploring the Tactile Perception Limits2013In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 3, p. 2617-Article in journal (Refereed)
    Abstract [en]

    The human finger is exquisitely sensitive in perceiving different materials, but the question remains as to what length scales are capable of being distinguished in active touch. We combine material science with psychophysics to manufacture and haptically explore a series of topographically patterned surfaces of controlled wavelength, but identical chemistry. Strain-induced surface wrinkling and subsequent templating produced 16 surfaces with wrinkle wavelengths ranging from 300 nm to 90 mu m and amplitudes between 7 nm and 4.5 mu m. Perceived similarities of these surfaces (and two blanks) were pairwise scaled by participants, and interdistances among all stimuli were determined by individual differences scaling (INDSCAL). The tactile space thus generated and its two perceptual dimensions were directly linked to surface physical properties - the finger friction coefficient and the wrinkle wavelength. Finally, the lowest amplitude of the wrinkles so distinguished was approximately 10 nm, demonstrating that human tactile discrimination extends to the nanoscale.

  • 291.
    Skjöldebrand, Charlotte
    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.
    Compositional Dependence Of Hardness And Modulus Of Sinfec Coatings2018In: 15th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering and 3rd Conference on Imaging and Visualization, Lisbon, Portugal 26-29 March, 2018 / [ed] P. R. Fernandes and J. M. Tavares, 2018Conference paper (Refereed)
  • 292.
    Skjöldebrand, Charlotte
    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.
    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.
    Biocompatibility of co-sputtered Si-Fe-C-N coatings2018Conference paper (Refereed)
    Abstract [en]

    INTRODUCTION: Hip joint arthroplasty is a common and increasingly frequent procedure that can relieve pain and restore mobility for individuals with e.g. severe osteoarthritis. While the procedure is common and to a large extent considered successful there is a need to prolong the lifespan of the implants to meet the need of a more active patient group, living longer. One of the main limiting factors behind the implant lifetime is the generation of particulate and ionic wear debris that causes an activation of the immune system. This debris originates in the articulating surfaces and one attempt to minimize the generation of debris is to deposit a ceramic coating on metal implant parts. The hard ceramic coatings, such as silicon nitride, could improve the wear resistance as well as act as a barrier for metal ion release.1,2 The silicon nitride coatings in this study were co-deposited with Fe and C in order to increase the deposition rate and tune the dissolution rate.

    METHODS: The coatings were deposited using reactive magnetron sputtering onto silicon wafer substrates. The Si target (99.99% purity) was powered with pulsed DC at 200 W, 200 kHz and 2 µs. The Fe target (99.99% purity) and C target (99.99% purity) were powered by DC aggregates at 25 W and 65 W respectively. The targets were positioned at an angle (38.81˚) and no rotation was used during deposition. Nitrogen was introduced as a reactive gas in addition to the inert Ar at a ratio of 0.3. The deposition time was 10 000 s.

    Based on the intended compositional gradients five points (4 corners in a square spaced 40 mm apart and the middle) on the sample were selected. No two points on the sample are identical and could be treated like individual samples.

    The composition was determined using ERDA and the surface properties were estimated with atomic force microscopy (AFM) in non-contact mode.

    The biocompatibility was assessed in vitro with osteo-progenitor cells from mouse (MC3T3)..

    RESULTS: The ERDA investigation revealed clear compositional gradients. The Si content ranged from 26 at.% in point 4 to 34 at.% in point 1. The Fe content changed in a complementary manner with a maximum of 20 at.% in point 4 and a minimum of 10 at.% in point 1. The carbon content ranged from 8 at.% in point 1 to 14 in point 4. In addition to the expected gradients the N content ranged from 40 at.% to 47 at.%.

    Despite the differences in composition the surface appearance and roughness remained similar for all the points (1-5) (Figure 1).

    The cell study showed surviving cells that adhered to the Si-N-Fe-C surface for all five points.

    DISCUSSION & CONCLUSIONS: Co-sputtering yielded compositional gradients along the silicon wafer. The unexpected gradient of N-content – N was present as a gas - is likely due to the ability of Si to form nitrides as seen from the low enthalpy of formation for Si3N4 (-743 kJ/mol). The low surface roughness is likely a consequence of the smooth Si-wafer substrate, it is however reasonable to assume that a polished metal substrate would also yield low surface roughness. The adhesion of the cells indicates biocompatibility. In summary the low surface roughness combined with the biocompatibility make the coatings interesting for further investigations.

     

    REFERENCES

    1.  Pettersson, M. et al. (2016) Mater. Sci. Eng. C. Mater. Biol. Appl. 62, 497–505 .

    2.  Pettersson, M. et al. (2013) J. Mech. Behav. Biomed. Mater. 25, 41–7.

     

    ACKNOWLEDGEMENTS: The research leading to these results has received funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under the LifeLongJoints Project, Grant Agreement no. GA-310477.

  • 293.
    Skjöldebrand, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. Material i Medicin gruppen.
    Hulsart Billström, Gry
    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.
    Combinatorial coating development of Si-N-Fe-C coatings for joint implants2018Conference paper (Refereed)
    Abstract [en]

    INTRODUCTION

    Joint replacements of hip and knee are generally considered successful procedures, with a survival rate of approximately 95% after 10 years. However, the increasing, more active elderly population puts higher demands on implants, which need to last longer. Some of the main limiting factors for the longevity of these implants are the generation of wear debris and release of metal ions. These wear particles and ion release could be reduced with the use of ceramic coatings e.g. silicon nitride. Silicon nitride coatings have in laboratory investigations been shown to reduce the wear rate1 and act as a barrier for metal ions and therefore warrant further investigation for use in joint implants. An addition of the biocompatible elements Fe and C could be used to tune the dissolution rate and increase the deposition rate.

    METHODS

    Coatings were deposited on silicon wafer substrates using magnetron co-sputtering. The targets used were Si (99.99%purity) powered by a pulsed DC aggregate at 200 W, 200 kHz and 2µs. The two other targets C and Fe were powered by DC aggregates at 65 W and 25 W respectively. During deposition N2 was introduced as reactive gas. Elemental gradients were obtained by angling of the targets and the use of no rotation.

    The coatings were investigated using elastic recoil detection analysis (ERDA), atomic force microscopy (AFM), scanning electron microscopy (SEM) and nanoindentation in five different points on the sample. The different points were chosen at coordinates (0,0), (0,40), (40,0), (40,40) and (20,20) based on a coordinate system with origin in the lower left corner.

    The cytotoxicity of the coatings was evaluated in vitro with mouse osteoprogenitor cells (MC3T3).

    RESULTS AND DISCUSSION

    Figure 1: Si, Fe, N and C composition over the substrate.

    Clear elemental gradients could be obtained with 26 wt.% < Si < 34 wt.%, 10 wt.% < Fe < 20 wt.%, 8 wt.% < C < 14 wt.% and 40 wt.% < N < 47 wt.% (figure 1). The coatings appeared dense in SEM surface analysis, with a smooth surface for all investigated points (Ra ~ 2 nm, AFM). The cross-sectional morphology was slightly columnar with broader columns for higher Fe content. The modulus (202 GPa < M < 221 GPa) correlated positively to the Si content and negatively to the Fe content while for the hardness (14 GPa < H < 18 GPa) no statistically significant correlations were found.  This can be compared to earlier coatings, only containing Si and N, which have showed a Young’s modulus of 170-240 GPa and a hardness of 12-26 GPa2, as well as the currently used metals such as CoCrMo, showing a Young’s modulus of 293 GPa and a hardness of 6 GPa2 .

    The in vitro evaluation indicated biocompatibility with viable cells that adhered and spread across the surface.

    CONCLUSIONS

    Si-N-Fe-C coatings show promise for applications exposed to wear with their low surface roughness, high hardness, high modulus and biocompatibility. These combined merit further investigations into the suitability of Si-N-Fe-C coatings for joint implants.

    REFERENCES

    1.           Pettersson, M. et al. Mechanical and tribological behavior of silicon nitride and silicon carbon nitride coatings for total joint replacements. J. Mech. Behav. Biomed. Mater. 25, 41–7 (2013).

    2.           Skjöldebrand, C. et al. Influence of substrate heating and nitrogen flow on the composition, morphological and mechanical properties of SiNx coatings aimed for joint replacements. Materials (Basel). 10, 1–11 (2017).

     

    ACKNOWLEDGEMENTS

    The research leading to these results has received funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under the LifeLongJoints Project, Grant Agreement no. GA-310477.

  • 294.
    Skyttner, Camilla
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Peptide-Liposome Model Systems for Triggered Release2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Liposomes are widely used in drug delivery to improve drug efficacy and to reduce side effects. For liposome-encapsulated drugs to become bioavailable and provide a therapeutic effect they must be released, which typically is a slow process that primarily relies on passive diffusion, liposome rupture or endocytotic uptake. Achieving drug concentrations within the therapeutic window can thus be challenging, resulting in poor efficacy and higher risks drug resistance. Finding means to modulate lipid membrane integrity and to trigger rapid and efficient release of liposomal cargo is thus critical to improve current and future liposomal drug delivery systems. The possibilities to tailor lipid composition and surface functionalization is vital for drug delivery applications but also make liposomes attractive model systems for studies of membrane active biomolecules.

    The overall aim of this thesis work has been to develop new strategies for triggering and controlling changes in lipid membrane integrity and to study the interactions of membrane active peptides with model lipid membranes using both de novo designed and biologically derived synthetic amphipathic cationic peptides. Two different sets of designed peptides have been explored that can fold and heterodimerize into a coiled coil and helix-loop-helix fourhelix bundle, respectively. Conjugation of the cationic lysine rich peptides to liposomes triggered a rapid and concentration dependent release. The additions of their corresponding glutamic acid-rich complementary peptides inhibited the release of liposomal cargo. Possibilities to reduce the inhibitory effect by both proteolytic digestion of the inhibitory peptide and by means of heterodimer exchange have been investigated. Moreover, the effects of peptide size and composition and ability to fold have been studied in order to elucidate the factors that influence the membrane permeabilizing effects of the peptides.

    In addition, the membrane activity of a the two-peptide bacteriocin PLNC8α and PLNC8β has been explored using liposomes as a model system. PLNC8αβ are expressed by Lactobacillus plantarum and were shown to display pronounced membrane-partition folding coupling, leading to rapid release of liposome encapsulated carboxyfluorescein. PLNC8αβ also kill and suppressed growth of the gram-negative bacteria Porphyromonas gingivalis by efficiently damaging the bacterial membrane.

    Although membrane active peptides are highly efficient in perturbing lipid membrane integrity, possibilities to trigger release using external stimuli are also of large interest for therapeutic applications. Light-induced heating of liposome encapsulated gold nanoparticles (AuNPs) has been shown by others as a potential strategy to trigger drug release. To facilitate fabrication of thermoplasmonic liposome systems we developed a simple method for synthesis of small AuNPs inside liposomes, using the liposomes as nanoscale reaction vessels.

    The work presented in this thesis provides new knowledge and techniques for future development of liposome-based drug delivery systems, peptide-based therapeutics and increase our understanding of peptide-lipid interactions.

  • 295.
    Sladkova, M.
    et al.
    New York Stem Cell Fdn Res Inst, New York, NY USA..
    Cheng, J.
    New York Stem Cell Fdn Res Inst, New York, NY USA..
    Lin, C.
    New York Stem Cell Fdn Res Inst, New York, NY USA..
    Palmer, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Chen, S. S.
    LifeNet Hlth, Virginia Beach, VA USA..
    Yu, Y. E.
    Columbia Univ, Fu Fdn Sch Engn & Appl Sci, New York, NY USA..
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    de Peppo, G. M.
    New York Stem Cell Fdn Res Inst, New York, NY USA..
    Bone Engineering Potential of Cow And Human Derived Decellularized Bone Scaffolds2016In: Tissue Engineering. Part A, ISSN 1937-3341, E-ISSN 1937-335X, Vol. 22, p. S16-S17Article in journal (Refereed)
  • 296.
    Sladkova, Martina
    et al.
    New York Stem Cell Fdn Res Inst, 619 West 54th St, New York, NY 10019 USA.
    Cheng, Jiayi
    New York Stem Cell Fdn Res Inst, 619 West 54th St, New York, NY 10019 USA.
    Palmer, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Chen, Silvia
    LifeNet Hlth Fdn, Virginia Beach, VA USA.
    Lin, Charles
    New York Stem Cell Fdn Res Inst, 619 West 54th St, New York, NY 10019 USA.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Yu, Yue Eric
    Columbia Univ, Dept Biomed Engn, New York, NY USA.
    Zhou, Bin
    Columbia Univ, Dept Biomed Engn, New York, NY USA.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    de Peppo, Giuseppe Maria
    New York Stem Cell Fdn Res Inst, 619 West 54th St, New York, NY 10019 USA.
    Comparison of Decellularized Cow and Human Bone for Engineering Bone Grafts with Human Induced Pluripotent Stem Cells2019In: Tissue Engineering. Part A, ISSN 1937-3341, E-ISSN 1937-335X, Vol. 25, no 3-4, p. 288-301Article in journal (Refereed)
    Abstract [en]

    Bone engineering makes it possible to grow unlimited amounts of viable tissue products for basic and applied research, and for clinical applications. A common trend in tissue engineering is the use of decellularized tissue matrices as scaffolding materials, which display structural, mechanical, and biological attributes typical of the native tissue. Due to the limited availability and high cost of human samples, decellularized tissue matrices are typically derived from animal sources. It is unclear, however, whether interspecies differences in tissue parameters will influence the quality of tissue grafts that are engineered using human stem cells. In this study, decellularized cow and human bone scaffolds were compared for engineering bone grafts using human induced pluripotent stem cell-derived mesodermal progenitor cells. After seeding, the cell-scaffold constructs were cultured for 5 weeks in osteogenic medium under dynamic conditions in perfusion bioreactors. The architectural and chemical properties of the scaffolds were studied using microscopic, spectroscopic, and thermogravimetric techniques, while cell behavior and formation of mineralized tissue were assessed using a combination of molecular assays, histological methods, and imaging technologies. The results show that while scaffolds derived from cow and human bone differ somewhat in architecture and composition, both equally support cell viability, tissue growth, and formation of a mineralized bone matrix. Taken together, the results suggest that scaffolds derived from cow bone represent a suitable and convenient alternative to engineer human bone grafts for various biomedical applications.

  • 297. Sommer, Gerhard
    et al.
    Schriefl, Andreas
    Zeindlinger, Georg
    Katzensteiner, Andreas
    Ainoedhofer, Herwig
    Saxena, Amulya
    Holzapfel, Gerhard A.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.).
    Multiaxial mechanical response and constitutive modeling of esophageal tissues: Impact on esophageal tissue engineering2013In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 9, no 12, p. 9379-9391Article in journal (Refereed)
    Abstract [en]

    Congenital defects of the esophagus are relatively frequent, with 1 out of 2500 babies suffering from such a defect. A new method of treatment by implanting tissue engineered esophagi into newborns is currently being developed and tested using ovine esophagi. For the reconstruction of the biological function of native tissues with engineered esophagi, their cellular structure as well as their mechanical properties must be considered. Since very limited mechanical and structural data for the esophagus are available, the aim of this study was to investigate the multiaxial mechanical behavior of the ovine esophagus and the underlying microstructure. Therefore, uniaxial tensile, biaxial tensile and extension-inflation tests on esophagi were performed. The underlying microstructure was examined in stained histological sections through standard optical microscopy techniques. Moreover, the uniaxial ultimate tensile strength and residual deformations of the tissue were determined. Both the mucosa-submucosa and the muscle layers showed nonlinear and anisotropic mechanical behavior during uniaxial, biaxial and inflation testing. Cyclical inflation of the intact esophageal tube caused marked softening of the passive esophagi in the circumferential direction. The rupture strength of the mucosa-submucosa layer was much higher than that of the muscle layer. Overall, the ovine esophagus showed a heterogeneous and anisotropic behavior with different mechanical properties for the individual layers. The intact and layer-specific multiaxial properties were characterized using a well-known three-dimensional microstructurally based strain-energy function. This novel and complete set of data serves the basis for a better understanding of tissue remodeling in diseased esophagi and can be used to perform computer simulations of surgical interventions or medical-device applications.

  • 298.
    Stenfelt, Sonya
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Hulsart-Billström, Gry
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Bergman, Kristoffer
    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.
    Bowden, Tim
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Pre-incubation of chemically crosslinked hyaluronan-based hydrogels, loaded with BMP-2 and hydroxyapatite, and its effect on ectopic bone formation2014In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 25, no 4, p. 1013-1023Article in journal (Refereed)
    Abstract [en]

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

  • 299. 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.

  • 300.
    Stevens, Raoul
    et al.
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.). Department of Biomedical Engineering, University of Technology, Eindhoven, The Netherlands.
    Grytsan, Andrii
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Biasetti, Jacopo
    Department of Mechanical Engineering, Johns Hopkins University, Baltimore, USA.
    Roy, Joy
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
    Lindquist Liljeqvist, Moritz
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
    Gasser, T.Christian
    KTH, School of Engineering Sciences (SCI), Solid Mechanics (Dept.), Biomechanics.
    Biomechanical changes during abdominal aortic aneurysm growth2016Report (Refereed)
    Abstract [en]

    The biomechanics-based Abdominal Aortic Aneurysm (AAA) rupture risk assessment has gainedconsiderable scientific and clinical momentum. However, such studies have mainly focused oninformation at a single time point, and little is known about how AAA properties change over time.Consequently, the present study explored how geometry, wall stress-related and blood flow-relatedbiomechanical properties change during AAA expansion. Four patients with a total of 23 ComputedTomography-Angiography (CT-A) scans at different time points were analyzed. At each time point,patient-specific properties were extracted from (i) the reconstructed geometry, (ii) the computedwall stress at Mean Arterial Pressure (MAP), and (iii) the computed blood flow velocity atstandardized in and out flow conditions. Testing correlations between these parameters identifiedseveral non-intuitive dependencies. Most interestingly, the Peak Wall Rupture Index (PWRI) and themaximum Wall Shear Stress (WSS) independently predicted AAA volume growth. Similarly, Intra-luminal Thrombus (ILT) volume growth depended on both the maximum WSS and the ILT volumeitself. In addition, ILT volume, ILT volume growth and maximum ILT layer thickness correlated withPWRI as well as AAA volume growth. Consequently, a large ILT volume as well as fast increase of ILTvolume over time may be a risk factor for AAA rupture. However, tailored clinical studies would berequired to test this hypothesis and to clarify whether monitoring ILT development has any clinicalbenefit.

345678 251 - 300 of 388
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