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  • 1.
    Ajalloueian, Fatemeh
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Zeiai, Said
    Fossum, Magdalena
    Hilborn, Jöns G.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Constructs of electrospun PLGA, compressed collagen and minced urothelium for minimally manipulated autologous bladder tissue expansion2014In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, no 22, p. 5741-5748Article in journal (Refereed)
    Abstract [en]

    Bladder regeneration based on minced bladder mucosa in vivo expansion is an alternative to in vitro culturing of urothelial cells. Here, we present the design of a hybrid, electrospun poly(lactic-co-glycolide) (PLGA) - plastically compressed (PC) collagen scaffold that could allow in vivo bladder mucosa expansion. Optimisation of electrospinning was performed in order to obtain increased pore sizes and porosity to consolidate the construct and to support neovascularisation and tissue ingrowth. Tensile tests showed an increase in average tensile strength from 0.6 MPa for PC collagen to 3.57 MPa for the hybrid construct. The optimised PLGA support scaffold was placed between two collagen gels, and the minced tissue was distributed either on top or both on top and inside the construct prior to PC; this was then cultured for up to four weeks. Morphology, histology and SEM demonstrated that the construct maintained its integrity throughout cell culture. Cells from minced tissue migrated, expanded and re-organised to a confluent cell layer on the top of the construct after two weeks and formed a multilayered urothelium after four weeks. Cell morphology and phenotype was typical for urothelial mucosa during tissue culture. (C) 2014 Elsevier Ltd. All rights reserved.

  • 2.
    Alarcon, Emilio I
    et al.
    University of Ottawa.
    Udekwu, Klas
    Karolinska Institute.
    Skog, Mårten
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Pacioni, NataliL
    University of Ottawa.
    Stamplecoskie, Kevin G
    University of Ottawa.
    Gonzalez-Bejar, Maria
    University of Ottawa.
    Polisetti, Naresh
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Wickham, Abeni
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics. Linköping University, The Institute of Technology.
    Richter-Dahlfors, Agneta
    Karolinska Institute.
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Ophthalmology. Linköping University, Faculty of Health Sciences.
    Scaiano, Juan C
    University of Ottawa.
    The biocompatibility and antibacterial properties of collagen-stabilized, photochemically prepared silver nanoparticles2012In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 33, no 19, p. 4947-4956Article in journal (Refereed)
    Abstract [en]

    Spherical 3.5 nm diameter silver nanoparticles (AgNP) stabilized in type I collagen (AgNP@collagen) were prepared in minutes (5-15 min) at room temperature by a photochemical method initiated by UVA irradiation of a water-soluble non-toxic benzoin. This biocomposite was examined to evaluate its biocompatibility and its anti-bacterial properties and showed remarkable properties. Thus, while keratinocytes and fibroblasts were not affected by AgNP@collagen, it was bactericidal against Bacillus megaterium and E. coli but only bacteriostatic against S. epidermidis. In particular, the bactericidal properties displayed by AgNP@collagen were proven to be due to AgNP in AgNP@collagen, rather than to released silver ions, since equimolar concentrations of Ag are about four times less active than AgNP@collagen based on total Ag content. This new biocomposite was stable over a remarkable range of NaCl, phosphate, and 2-(N-morpholino)ethanesulfonic acid concentrations and for over one month at 4 degrees C. Circular dichroism studies show that the conformation of collagen in AgNP@collagen remains intact. Finally, we have compared the properties of AgNP@collagen with a similar biocomposite prepared using alpha-poly-L-Lysine and also with citrate stabilized AgNP; neither of these materials showed comparable biocompatibility, stability, or anti-bacterial activity.

  • 3.
    Almlöf, Martin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Kristensen, Emma M. E.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics.
    Siegbahn, Hans
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics.
    Åqvist, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Molecular dynamics study of heparin based coatings2008In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 29, no 33, p. 4463-4469Article in journal (Refereed)
    Abstract [en]

    Heparin based surface coatings can be used to improve the biocompatibility of metallic surfaces such as vascular stents. Here, we report molecular dynamics simulations of a macromolecular conjugate of heparin used to prepare such surfaces. The structural properties of the heparin conjugate are investigated for different degrees of hydration, to allow comparison with spectroscopic results. The simulations show that the polymer becomes more compact with an increasing degree of inter-chain interactions as the hydration increases. This is also accompanied by changes in the interaction patterns among the heparin chains, where counter ions become looser associated with the disaccharide units and their strong interactions can be partly replaced by water molecules and heparin hydroxyl groups. The structural information that can be obtained from computer simulations of this type of coatings can be very valuable for understanding and further development of functional interfaces, since very little is known experimentally regarding their detailed structural properties. (C) 2008 Elsevier Ltd. All rights reserved.

  • 4.
    Arvidsson, Sara
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    Askendal, Agneta
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    Tengvall, Pentti
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    Blood plasma contact activation on silicon titanium and aluminium2007In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 28, p. 1346-1354Article in journal (Refereed)
    Abstract [en]

       

  • 5. Bayat, N
    et al.
    Lopes, Viviana
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Jensen, LD
    Cristobal, S
    Vascular toxicity of ultra-small TiO2 nanoparticles and single walled carbon nanotubes in vitro and in vivo2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 63, p. 1-13Article in journal (Refereed)
    Abstract [en]

    Ultra-small nanoparticles (USNPs) at 1-3 nm are a subset of nanoparticles (NPs) that exhibit intermediate physicochemical properties between molecular dispersions and larger NPs. Despite interest in their utilization in applications such as theranostics, limited data about their toxicity exist. Here the effect of TiO2-USNPs on endothelial cells in vitro, and zebrafish embryos in vivo, was studied and compared to larger TiO2-NPs (30 nm) and to single walled carbon nanotubes (SWCNTs). In vitro exposure showed that TiO2-USNPs were neither cytotoxic, nor had oxidative ability, nevertheless were genotoxic. In vivo experiment in early developing zebrafish embryos in water at high concentrations of TiO2-USNPs caused mortality possibly by acidifying the water and caused malformations in the form of pericardial edema when injected. Myo1C involved in glomerular development of zebrafish embryos was upregulated in embryos exposed to TiO2-USNPs. They also exhibited anti-angiogenic effects both in vitro and in vivo plus decreased nitric oxide concentration. The larger TiO2-NPs were genotoxic but not cytotoxic. SWCNTs were cytotoxic in vitro and had the highest oxidative ability. Neither of these NPs had significant effects in vivo. To our knowledge this is the first study evaluating the effects of TiO2-USNPs on vascular toxicity in vitro and in vivo and this strategy could unravel USNPs potential applications.

  • 6.
    Bayat, Narges
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Lopes, Viviana R.
    Schoelermann, Julia
    Dahl Jensen, Lasse
    Cristobal, Susana
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Vascular toxicity of ultra-small TiO2 nanoparticles and single walled carbon nanotubes in vitro and in vivo2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 63, p. 1-13Article in journal (Refereed)
    Abstract [en]

    Ultra-small nanoparticles (USNPs) at 1-3 nm are a subset of nanoparticles (NPs) that exhibit intermediate physicochemical properties between molecular dispersions and larger NPs. Despite interest in their utilization in applications such as theranostics, limited data about their toxicity exist. Here the effect of TiO2-USNPs on endothelial cells in vitro, and zebrafish embryos in vivo, was studied and compared to larger TiO2-NPs (30 nm) and to single walled carbon nanotubes (SWCNTs). In vitro exposure showed that TiO2-USNPs were neither cytotoxic, nor had oxidative ability, nevertheless were genotoxic. In vivo experiment in early developing zebrafish embryos in water at high concentrations of TiO2-USNPs caused mortality possibly by acidifying the water and caused malformations in the form of pericardial edema when injected. Myo1C involved in glomerular development of zebrafish embryos was upregulated in embryos exposed to TiO2-USNPs. They also exhibited anti-angiogenic effects both in vitro and in vivo plus decreased nitric oxide concentration. The larger TiO2-NPs were genotoxic but not cytotoxic. SWCNTs were cytotoxic in vitro and had the highest oxidative ability. Neither of these NPs had significant effects in vivo. To our knowledge this is the first study evaluating the effects of TiO2-USNPs on vascular toxicity in vitro and in vivo and this strategy could unravel USNPs potential applications.

  • 7.
    Bayat, Narges
    et al.
    Stockholm University, Sweden.
    Lopes, Viviana
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Schoelermann, Julia
    University of Bergen, Norway.
    Jensen, Lasse
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Cristobal, Susana
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Stockholm University, Sweden; University of Basque Country, Spain.
    Vascular toxicity of ultra-small TiO2 nanoparticles and single walled carbon nanotubes in vitro and in vivo2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 63Article in journal (Refereed)
    Abstract [en]

    Ultra-small nanoparticles (USNPs) at 1-3 nm are a subset of nanoparticles (NPs) that exhibit intermediate physicochemical properties between molecular dispersions and larger NPs. Despite interest in their utilization in applications such as theranostics, limited data about their toxicity exist. Here the effect of TiO2-USNPs on endothelial cells in vitro, and zebrafish embryos in vivo, was studied and compared to larger TiO2-NPs (30 nm) and to single walled carbon nanotubes (SWCNTs). In vitro exposure showed that TiO2-USNPs were neither cytotoxic, nor had oxidative ability, nevertheless were genotoxic. In vivo experiment in early developing zebrafish embryos in water at high concentrations of TiO2-USNPs caused mortality possibly by acidifying the water and caused malformations in the form of pericardial edema when injected. Myo1C involved in glomerular development of zebrafish embryos was upregulated in embryos exposed to TiO2-USNPs. They also exhibited anti-angiogenic effects both in vitro and in vivo plus decreased nitric oxide concentration. The larger TiO2-NPs were genotoxic but not cytotoxic. SWCNTs were cytotoxic in vitro and had the highest oxidative ability. Neither of these NPs had significant effects in vivo. To our knowledge this is the first study evaluating the effects of TiO2-USNPs on vascular toxicity in vitro and in vivo and this strategy could unravel USNPs potential applications. (C) 2015 Elsevier Ltd. All rights reserved.

  • 8.
    Benesch, Johan
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology.
    Tengvall, Pentti
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    Blood protein adsorption onto chitosan2002In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 23, no 12, p. 2561-2568Article in journal (Refereed)
    Abstract [en]

    Chitosan was recently indicated to enhance osteogenesis, improve wound healing but to activate the coagulation and the complement systems. In the present study approximately 10nm thick chitosan film were prepared on aminopropyltriethoxysilane (APTES) coated silicon. The surfaces were incubated in serum or plasma and subsequently in antibodies towards key complement and contact activation of coagulation proteins. The deposited amounts were compared with those on hydrophilic and hydrophobic silicon, APTES and IgG coated reference samples. Although large amounts of serum deposited to chitosan only a weak transient activation of the complement system and no activation of the intrinsic pathway was observed. Upon acetylation the chitosan layer became a strong activator of the alternative pathway of the complement. After incubation in human plasma anti-fibrinogen deposited onto chitosan but not onto the acetylated chitosan, a finding that may explain previous observations of procoagulant activity by chitosan. Copyright © 2002 Elsevier Science Ltd.

  • 9. Blau, Axel
    et al.
    Murr, Angelika
    Wolff, Sandra
    Sernagor, Evelyne
    Medini, Paolo
    Iurilli, Giuliano
    Ziegler, Christiane
    Benfenati, Fabio
    Flexible, all-polymer microelectrode arrays for the capture of cardiac and neuronal signals2011In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 32, no 7, p. 1778-1786Article in journal (Refereed)
    Abstract [en]

    Microelectrode electrophysiology has become a widespread technique for the extracellular recording of bioelectrical signals. To date, electrodes are made of metals or inorganic semiconductors, or hybrids thereof. We demonstrate that these traditional conductors can be completely substituted by highly flexible electroconductive polymers. Pursuing a two-level replica-forming strategy, conductive areas for electrodes, leads and contact pads are defined as microchannels in poly(dimethylsiloxane) (PDMS) as a plastic carrier and track insulation material. These channels are coated by films of organic conductors such as polystyrenesulfonate-doped poly(3,4-ethylenedioxy-thiophene) (PEDOT:PSS) or filled with a graphite-PDMS (gPDMS) composite, either alone or in combination. The bendable, somewhat stretchable, non-cytotoxic and biostable all-polymer microelectrode arrays (polyMEAs) with a thickness below 500 μm and up to 60 electrodes reliably capture action potentials (APs) and local field potentials (LFPs) from acute preparations of heart muscle cells and retinal whole mounts, in vivo epicortical and epidural recordings as well as during long-term in vitro recordings from cortico-hippocampal co-cultures.

  • 10. Broos, Sissela
    et al.
    Sandin, Linda C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Apel, Jenny
    Tötterman, Thomas H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Akagi, Takami
    Akashi, Mitsuru
    Borrebaeck, Carl A. K.
    Ellmark, Peter
    Lindstedt, Malin
    Synergistic augmentation of CD40-mediated activation of antigen-presenting cells by amphiphilic poly(gamma-glutamic acid) nanoparticles2012In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 33, no 26, p. 6230-6239Article in journal (Refereed)
    Abstract [en]

    Agonistic anti-CD40 monoclonal antibodies (mAbs) hold great potential for cancer immunotherapy. However, systemic administration of anti-CD40 mAbs can be associated with severe side effects, such as cytokine release syndrome and liver damage. With the aim to increase the immunostimulatory potency as well as to achieve a local drug retention of anti-CD40 mAbs, we linked an agonistic mAb to immune activating amphiphilic poly(gamma-glutamic acid) nanoparticles (gamma-PGA NPs). We demonstrate that adsorption of anti-CD40 mAb to gamma-PGA NPs (anti-CD40-NPs) improved the stimulatory capacity of the CD40 agonist, resulting in upregulation of costimulatory CD80 and CD86 on antigen-presenting cells, as well as IL-12 secretion. Interestingly, anti-CD40-NP5 induced strong synergistic proliferative effects in B cells, possibly resulting from a higher degree of CD40 multimerization, enabled by display of multiple anti-CD40 mAbs on the NPs. In addition, local treatment with anti-CD40-NPs, compared to only soluble CD40 agonist, resulted in a significant reduction in serum levels of IL-6, IL-10, IL-12 and TNF-alpha in a bladder cancer model. Taken together, our results suggest that anti-CD40-NPs are capable of synergistically enhancing the immunostimulatory effect induced by the CD40 agonist, as well as minimizing adverse side effects associated with systemic cytokine release. This concept of nanomedicine could play an important role in localized immunotherapy of cancer.

  • 11. Bäck, Jennie
    et al.
    Huber-Lang, Markus
    Elgue, Graciela
    Kalbitz, Miriam
    Sanchez, Javier
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Nilsson, Bo
    Distinctive regulation of contact activation by antithrombin and C1-inhibitor on activated platelets and material surfaces2009In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 30, no 34, p. 6573-6580Article in journal (Refereed)
    Abstract [en]

    Activated human plate lets trigger FXII-mediated contactactivation, which leads to the generation of FXIIa–antithrombin (AT) and FXIa–AT complexes. This suggests that contactactivation takes place at different sites, on activatedplatelets and material surfaces, during therapeutic procedures involving biomaterials in contact with blood and is differentially regulated. Here we show that activation in platelet-poor plasma, platelet-rich plasma (PRP), and whole blood induced by glass, kaolin, and polyphosphate elicited high levels of FXIIa-C1-inhibitor (C1INH), low levels of FXIa–C1INH and KK–C1INH, and almost no AT complexes. Plateletactivation, in both PRP and blood, led to the formation of FXIIa–AT, FXIa–AT, and kallikrein (KK)–AT but almost no C1INH complexes. In severe trauma patients, FXIIa–AT and FXIa–AT were correlated with the release of thrombospondin-1 (TSP-1) from activatedplatelets. In contrast, FXIIa–C1INH complexes were detected when the FXIIa–AT levels were low. No correlations were found between FXIIa–C1INH and FXIIa–AT or TSP-1. Inhibition of FXIIa on material surfaces was also shown to affect the function of aggregating platelets. In conclusion, formation of FXIIa–AT and FXIIa–C1INH complexes can help to distinguish between contactactivation triggered by biomaterial surfaces and by activatedplatelets. Platelet aggregation studies also demonstrated that platelet function is influenced by material surface-mediated contactactivation and that generation of FXIIa–AT complexes may serve as a new biomarker for thrombotic reactions during therapeutic procedures employing biomaterial devices.

  • 12.
    Bäck, Jennie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Lang, Markus Huber
    Elgue, Graciela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Kalbitz, Miriam
    Sanchez, Javier
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ekdahl, Kristina Nilsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Distinctive regulation of contact activation by antithrombin and C1-inhibitor on activated platelets and material surfaces2009In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 30, no 34, p. 6573-6580Article in journal (Refereed)
    Abstract [en]

    Activated human plate lets trigger FXII-mediated contact activation, which leads to the generation of FXIIa-antithrombin (AT) and FXIa-AT complexes. This suggests that contact activation takes place at different sites, on activated platelets and material surfaces, during therapeutic procedures involving biomaterials in contact with blood and is differentially regulated. Here we show that activation in platelet-poor plasma, platelet-rich plasma (PRP), and whole blood induced by glass, kaolin, and polyphosphate elicited high levels of FXIIa-C1-inhibitor (C1INH), low levels of FXIa-C1INH and KK-C1INH, and almost no AT complexes. Platelet activation, in both PRP and blood, led to the formation of FXIIa-AT, FXIa-AT, and kallikrein (KK)-AT but almost no C1INH complexes. In severe trauma patients, FXIIa-AT and FXIa-AT were correlated with the release of thrombospondin-1 (TSP-1) from activated platelets. In contrast, FXIIa-C1INH complexes were detected when the FXIIa-AT levels were low. No correlations were found between FXIIa-C1INH and FXIIa-AT or TSP-1. Inhibition of FXIIa on material surfaces was also shown to affect the function of aggregating platelets. In conclusion, formation of FXIIa-AT and FXIIa-C1INH complexes can help to distinguish between contact activation triggered by biomaterial surfaces and by activated platelets. Platelet aggregation studies also demonstrated that platelet function is influenced by material surface-mediated contact activation and that generation of FXIIa-AT complexes may serve as a new biomarker for thrombotic reactions during therapeutic procedures employing biomaterial devices.

  • 13.
    Cardemil, Carina
    et al.
    Department of Biomaterials, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden; Department of Oral and Maxillofacial Surgery, Örebro University Hospital, Örebro, Sweden; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Göteborg, Sweden.
    Omar, Omar M.
    Department of Biomaterials, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Göteborg, Sweden.
    Norlindh, Birgitta
    Department of Biomaterials, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Göteborg, Sweden.
    Wexell, Cecilia L.
    Department of Biomaterials, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Göteborg, Sweden; Department of Oral and Maxillofacial Surgery, Institute of Odontology, Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden.
    Thomsen, Peter
    Department of Biomaterials, Institute of Clinical Sciences, The Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden; Department of Oral and Maxillofacial Surgery, Örebro University Hospital, Örebro, Sweden; BIOMATCELL VINN Excellence Center of Biomaterials and Cell Therapy, Göteborg, Sweden.
    The effects of a systemic single dose of zoledronic acid on post-implantation bone remodelling and inflammation in an ovariectomised rat model.2013In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 34, no 5, p. 1546-1561Article in journal (Refereed)
    Abstract [en]

    Bisphosphonates reverse the negative effects of ovariectomy on bone, but they have also been associated with adverse processes in human jawbone. The molecular events determining bone regeneration and implant integration in osteoporotic conditions, with and without bisphosphonate treatment, are unclear. In this study, ovariectomised rats, to which a single dose of saline (NaCl) or zoledronic acid (Zol) was administered, received titanium alloy implants in their tibiae and mandibles. An enzyme-linked immunosorbent assay, gene expression analysis and histomorphometry were performed. The results show that ovariectomy, per se, upregulated the expression of genes denoting bone formation in the tibia, bone remodelling in the mandible and apoptosis in the tibia and mandible. Zoledronic acid administration resulted in lower levels of a remodelling marker in serum and downregulated gene expression for inflammation, bone formation, angiogenesis and apoptosis, mainly in the mandible, after 28 d of healing. Histomorphometry revealed improved bone-to-implant contact in the tibia, while the opposite was observed in the mandible. The present data show that a systemic single dose of zoledronic acid, in ovariectomised animals, results in site-specific differences in the regulation of genes involved in bone healing and regeneration in association with implant installation. These events occur in parallel with site-specific differences in the rate of osseointegration, indicating diverse tissue responses in the tibia and mandible after zoledronic acid treatment. The zoledronic acid effect on gene expression, during the late phase of healing in the mandible, suggests negative effects by the anti-resorptive agent on osseointegration at that particular site.

  • 14.
    Carlson, Johan
    et al.
    Luleå University of Technology, Department of Computer Science, Electrical and Space Engineering, Signals and Systems.
    Nilsson, M
    Polytechnical University of Catalonia, Barcelona.
    Fernández, E.
    Polytechnical University of Catalonia, Barcelona.
    Planell, J. A.
    Polytechnical University of Catalonia, Barcelona.
    An ultrasonic pulse-echo technique for monitoring the setting of CaSO4-based bone cement2003In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 24, no 1, p. 71-77Article in journal (Refereed)
    Abstract [en]

    We present a new ultrasonic technique for monitoring the entire setting process of injectable bone cement. The problem with existing standards is their subjectivity. Because of this the results are not comparable between different research groups. A strong advantage with the proposed technique is that it is non-invasive and non-destructive, since no manipulation of the cement sample is needed once the measurement has started. Furthermore, the results are reproducible with small variations. The testing was performed on calcium sulfate cement using an ultrasonic pulse-echo approach. The results show that the acoustic properties of the cement are strongly correlated with the setting time, the density, and the adiabatic bulk modulus. The measured initial and final setting times agree well with the Gillmore needles standard. An important difference compared to the standards, is that the technique presented here allows the user to follow the entire setting process on-line.

  • 15. Carlén, A
    et al.
    Nikdel, K
    Wennerberg, A
    Holmberg, K
    YKI – Ytkemiska institutet.
    Olsson, J
    Surface characteristics and in vitro biofilm formation on glass ionomer and composite resin2001In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 22, p. 481-487Article in journal (Refereed)
    Abstract [en]

    In the initial stages of dental plaque formation, early colonizing bacteria bind to receptor structures in the pellicle, a proteinaceous film formed instantly after cleaning of the tooth surface. Dental restorative materials with surface characteristics different from the tooth might affect pellicle formation and the ability of bacteria to colonize the oral cavity. in this study (i) roughness and chemical composition of glass ionomer and composite resin surfaces before and after polishing, and (ii) the adsorption of salivary proteins and bacterial adherence to the pellicle-coated surfaces were examined. Compared with unpolished composite resin, unpolished glass ionomer had higher surface roughness, contained more inorganic, positively charged components, collected more proteins, and promoted better bacterial adherence. Polishing had the most pronounced effect on the composite resin, giving an enlarged and a rougher surface with a more inorganic character. Polishing the composite resin also led to increased biofilm formation

  • 16. Constantinidis, Ioannis
    et al.
    Grant, Samuel C.
    Celper, Susanne
    KTH.
    Gauffin-Holmberg, Isabel
    KTH.
    Agering, Kristina
    KTH.
    Oca-Cossio, Jose A.
    Bui, Jonathan D.
    Flint, Jeremy
    Hamaty, Christine
    Simpson, Nicholas E.
    Blackband, Stephen J.
    Non-invasive evaluation of alginate/poly-L-lysine/alginate microcapsules by magnetic resonance microscopy2007In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 28, no 15, p. 2438-2445Article in journal (Refereed)
    Abstract [en]

    In this report, we present data to demonstrate the utility of H-1 MR microscopy to non-invasively examine alginate/poly-L-lysine/ alginate (APA) microcapsules. Specifically, high-resolution images were used to visualize and quantify the poly-L-lysine (PLL) layer, and monitor temporal changes in the alginate gel microstructure during a month long in vitro culture. The thickness of the alginate/PLL layer was quantified to be 40.6 +/- 6.2 mu m regardless of the alginate composition used to generate the beads or the time of alginate/PLL interaction (2, 6, or 20 min). However, there was a notable difference in the contrast of the PLL layer that depended upon the guluronic content of the alginate and the alginate/PLL interaction time. The T-2 relaxation time and the apparent diffusion coefficient (ADC) of the alginate matrix were measured periodically throughout the month long culture period. Alginate beads generated with a high guluronic content alginate demonstrated a temporal decrease in T-2 over the duration of the experiment, while ADC was unaffected. This decrease in T-2 is attributed to a reorganization of the alginate microstructure due to periodic media exchanges that mimicked a regular feeding regiment for cultured cells. In beads coated with a PLL layer, this temporal decrease in T-2 was less pronounced suggesting that the PLL layer helped maintain the integrity of the initial alginate microstructure. Conversely, alginate beads generated with a high mannuronic content alginate (with or without a PLL layer) did not display temporal changes in either T-2 or ADC. This observation suggests that the microstructure of high mannuronic content alginate beads is less susceptible to culture conditions.

  • 17.
    Coutu, Daniel L
    et al.
    McGill University, Montreal, Canada.
    Cuerquis, Jessica
    McGill University, Montreal, Canada.
    El Ayoubi, Rouwayda
    Natl Res Council Canada, Boucherville, Canada.
    Forner, Kathy-Ann
    McGill University, Montreal, Canada.
    Roy, Ranjan
    McGill University, Montreal, Canada.
    Francois, Moira
    McGill University, Montreal, Canada.
    Griffith, May
    Ottawa Health Research Institute, Ottawa, Canada.
    Lillicrap, David
    Queen’s University, Kingston, Canada.
    Yousefi, Azizeh-Mitra
    Natl Res Council Canada, Boucherville, Canada.
    Blostein, Mark D
    McGill University, Montreal, Canada.
    Galipeau, Jacques
    McGill University, Montreal, Canada.
    Hierarchical scaffold design for mesenchymal stem cell-based gene therapy of hemophilia B2011In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 32, no 1, p. 295-305Article in journal (Refereed)
    Abstract [en]

    Gene therapy for hemophilia B and other hereditary plasma protein deficiencies showed great promise in pre-clinical and early clinical trials. However, safety concerns about in vivo delivery of viral vectors and poor post-transplant survival of ex vivo modified cells remain key hurdles for clinical translation of gene therapy. We here describe a 3D scaffold system based on porous hydroxyapatite PLGA composites coated with biomineralized collagen 1. When combined with autologous gene-engineered factor IX (hFIX) positive mesenchymal stem cells (MSCs) and implanted in hemophilic mice, these scaffolds supported long-term engraftment and systemic protein delivery by MSCs in vivo. Optimization of the scaffolds at the macro-, micro- and nanoscales provided efficient cell delivery capacity, MSC self-renewal and osteogenesis respectively, concurrent with sustained delivery of hFIX. In conclusion, the use of gene-enhanced MSC-seeded scaffolds may be of practical use for treatment of hemophilia B and other plasma protein deficiencies.

  • 18.
    da Silva, Joakim
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics.
    Lautenschläger, Franziska
    Sivaniah, Easan
    Guck, Jochen R.
    The cavity-to-cavity migration of leukaemic cells through 3D honey-combed hydrogels with adjustable internal dimension and stiffness2010In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 31, no 8, p. 2201-2208Article in journal (Refereed)
    Abstract [en]

    Whilst rigid, planar surfaces are often used to study cell migration, a physiological scenario requires three-dimensional (3D) scaffolds with tissue-like stiffness. This paper presents a method for fabricating periodic hydrogel scaffolds with a 3D honeycomb-like structure from colloidal crystal templates. The scaffolds, made of hydrogel-walled cavities interconnected by pores, have separately tuneable internal dimensions and adjustable gel stiffness down to that of soft tissues. In conjunction with confocal microscopy, these scaffolds were used to study the importance of cell compliance on invasive potential. Acute promyelocytic leukaemia (APL) cells were differentiated with all-trans retinoic acid (ATRA) and treated with paclitaxel. Their migration ability into the scaffolds' size-restricted pores, enabled by cell softening during ATRA differentiation, was significantly reduced by paclitaxel treatment, which interferes with cell shape recovery. These findings demonstrate the usability of the scaffolds for investigating factors that affect cell migration, and potentially other cell functions, in a realistic 3D tissue model.

  • 19.
    Dekki Shalaly, Nancy
    et al.
    KTH, School of Biotechnology (BIO), Protein Technology.
    Ria, Massimiliano
    Johansson, Ulrika
    KTH, School of Biotechnology (BIO), Protein Technology.
    Avall, Karin
    Berggren, Per-Olof
    Hedhammar, My
    KTH, School of Biotechnology (BIO), Protein Technology.
    Silk matrices promote formation of insulin-secreting islet-like clusters2016In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 90, p. 50-61Article in journal (Refereed)
    Abstract [en]

    Ex vivo expansion of endocrine cells constitutes an interesting alternative to be able to match the unmet need of transplantable pancreatic islets. However, endocrine cells become fragile once removed from their extracellular matrix (ECM) and typically become senescent and loose insulin expression during conventional 2D culture. Herein we develop a protocol where 3D silk matrices functionalized with ECM derived motifs are used for generation of insulin-secreting islet-like clusters from mouse and human primary cells. The obtained clusters were shown to attain an islet-like spheroid shape and to maintain functional insulin release upon glucose stimulation in vitro. Furthermore, in vivo imaging of transplanted murine clusters showed engraftment with increasing vessel formation during time. There was no sign of cell death and the clusters maintained or increased in size throughout the period, thus suggesting a suitable cluster size for transplantation.

  • 20.
    Dong, Yihui
    et al.
    Nanjing Tech Univ, State Key Lab Mat Oriented & Chem Engn, Nanjing 210009, Jiangsu, Peoples R China;Nanjing Tech Univ, Jiangsu Natl Synerget Innovat Ctr Adv Mat SICAM, Nanjing 210009, Jiangsu, Peoples R China;Luled Univ Technol, Div Energy Sci, S-97187 Lulea, Sweden.
    Ji, Xiaoyan
    Luled Univ Technol, Div Energy Sci, S-97187 Lulea, Sweden.
    Laaksonen, Aatto
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry. Nanjing Tech Univ, State Key Lab Mat Oriented & Chem Engn, Nanjing 210009, Jiangsu, Peoples R China;Nanjing Tech Univ, Jiangsu Natl Synerget Innovat Ctr Adv Mat SICAM, Nanjing 210009, Jiangsu, Peoples R China;Stockholm Univ, Dept Mat & Environm Chem, Arrhenius Lab, SE-10691 Stockholm, Sweden;Petru Poni Inst Macromol Chem, Ctr Adv Res Bionanoconjugates & Biopolymers, Aleea Grigore Ghica Voda 41A, Iasi 700487, Romania.
    Cao, Wei
    Tsinghua Univ, State Key Lab Tribol, Beijing 100084, Peoples R China.
    An, Rong
    Nanjing Univ Sci & Technol, Herbert Gleiter Inst Nanosci, Nanjing 210094, Jiangsu, Peoples R China.
    Lu, Linghong
    Nanjing Tech Univ, State Key Lab Mat Oriented & Chem Engn, Nanjing 210009, Jiangsu, Peoples R China;Nanjing Tech Univ, Jiangsu Natl Synerget Innovat Ctr Adv Mat SICAM, Nanjing 210009, Jiangsu, Peoples R China.
    Lu, Xiaohua
    Nanjing Tech Univ, State Key Lab Mat Oriented & Chem Engn, Nanjing 210009, Jiangsu, Peoples R China;Nanjing Tech Univ, Jiangsu Natl Synerget Innovat Ctr Adv Mat SICAM, Nanjing 210009, Jiangsu, Peoples R China.
    Determination of the small amount of proteins interacting with TiO2 nanotubes by AFM-measurement2019In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 192, p. 368-376Article in journal (Refereed)
    Abstract [en]

    Detecting the small amounts of proteins interacting effectively with the solid film electrodes surface still remains a challenge. To address this, in this work, a new approach was proposed by the combination of the adhesion forces and the molecular interaction measured with AFM. Cytochrome c (Cyt C) interacting effectively with TiO2 nanotube arrays (TNAs) was chosen as a probe. The amounts of Cyt C molecules interacting effectively on TNAs surface (C-TNA) range from 5.5x10(-12) to 7.0x10(-12) mol/cm(2) (68.2-86.8 ng/cm(2)) and they are comparable with the values obtained by the electrochemistry method in the literature, in evidence of the accuracy of this AFM-based approach. The reliability of the proposed approach was further verified by conducting Surface Enhanced Raman Scattering (SERS) measurements and estimating the enhancement factor (EF). This interaction-based AFM approach can be used to accurately obtain the small amounts of adsorbed substances on the solid film electrodes surface in the applications such as biosensors, biocatalysis, and drug delivery, etc.

  • 21. Dong, Yihui
    et al.
    Ji, Xiaoyan
    Laaksonen, Aatto
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Nanjing Tech University, China; Uppsala University, Sweden; Petru Poni Institute of Macromolecular Chemistry, Romania.
    Cao, Wei
    An, Rong
    Lu, Linghong
    Lu, Xiaohua
    Determination of the small amount of proteins interacting with TiO2 nanotubes by AFM-measurement2019In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 192, p. 368-376Article in journal (Refereed)
    Abstract [en]

    Detecting the small amounts of proteins interacting effectively with the solid film electrodes surface still remains a challenge. To address this, in this work, a new approach was proposed by the combination of the adhesion forces and the molecular interaction measured with AFM. Cytochrome c (Cyt C) interacting effectively with TiO2 nanotube arrays (TNAs) was chosen as a probe. The amounts of Cyt C molecules interacting effectively on TNAs surface (C-TNA) range from 5.5x10(-12) to 7.0x10(-12) mol/cm(2) (68.2-86.8 ng/cm(2)) and they are comparable with the values obtained by the electrochemistry method in the literature, in evidence of the accuracy of this AFM-based approach. The reliability of the proposed approach was further verified by conducting Surface Enhanced Raman Scattering (SERS) measurements and estimating the enhancement factor (EF). This interaction-based AFM approach can be used to accurately obtain the small amounts of adsorbed substances on the solid film electrodes surface in the applications such as biosensors, biocatalysis, and drug delivery, etc.

  • 22.
    Dong, Yihui
    et al.
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Energy Science. State Key Laboratory of Materials-Oriented and Chemical Engineering and Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, Nanjing, China.
    Ji, Xiaoyan
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Energy Science.
    Laaksonen, Aatto
    State Key Laboratory of Materials-Oriented and Chemical Engineering and Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, Nanjing, China. Department of Materials and Environmental Chemistry, Arrhenius Laboratory, Stockholm University, Stockholm, Sweden. Department of Chemistry, Ångström Laboratory, Uppsala University, Uppsala, Sweden. Centre of Advanced Research in Bionanoconjugates and Biopolymers, Petru Poni Institute of Macromolecular Chemistry Aleea Grigore Ghica-Voda, Iasi, Romania.
    Cao, Wei
    State Key Laboratory of Tribology, Tsinghua University, Beijing, China.
    An, Rong
    Herbert Gleiter Institute of Nanoscience, Nanjing University of Science & Technology, Nanjing, China.
    Lu, Linghong
    State Key Laboratory of Materials-Oriented and Chemical Engineering and Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, Nanjing, China.
    Lu, Xiaohua
    State Key Laboratory of Materials-Oriented and Chemical Engineering and Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, Nanjing, China.
    Determination of the small amount of proteins interacting with TiO2 nanotubes by AFM-measurement2019In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 192, p. 368-376Article in journal (Refereed)
    Abstract [en]

    Detecting the small amounts of proteins interacting effectively with the solid film electrodes surface still remains a challenge. To address this, in this work, a new approach was proposed by the combination of the adhesion forces and the molecular interaction measured with AFM. Cytochrome c (Cyt C) interacting effectively with TiO2 nanotube arrays (TNAs) was chosen as a probe. The amounts of Cyt C molecules interacting effectively on TNAs surface (CTNA) range from 5.5×10-12 to 7.0×10-12 mol/cm2 (68.2-86.8 ng/cm2) and they are comparable with the values obtained by the electrochemistry method in the literature, in evidence of the accuracy of this AFM-based approach. The reliability of the proposed approach was further verified by conducting Surface Enhanced Raman Scattering (SERS) measurements and estimating the enhancement factor (EF). This interaction-based AFM approach can be used to accurately obtain the small amounts of adsorbed substances on the solid film electrodes surface in the applications such as biosensors, biocatalysis, and drug delivery, etc.

  • 23. Douglas, T. A.
    et al.
    Tamburro, Davide
    Fredolini, C.
    Espina, B. H.
    Lepene, B. S.
    Ilag, Leopold
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Espina, V.
    Petricoin, E. F.
    Liotta, L. A.
    Luchini, A.
    The use of hydrogel microparticles to sequester and concentrate bacterial antigens in a urine test for Lyme disease2011In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 32, no 4, p. 1157-1166Article in journal (Refereed)
    Abstract [en]

    Hydrogel biomarker capturing microparticles were evaluated as a biomaterial to amplify the sensitivity of urine testing for infectious disease proteins. Lyme disease is a bacterial infection transmitted by ticks. Early diagnosis and prompt treatment of Lyme disease reduces complications including arthritis and cardiac involvement. While a urine test is highly desirable for Lyme disease screening, this has been difficult to accomplish because the antigen is present at extremely low concentrations, below the detection limit of clinical immunoassays. N-isopropylacrylamide (NIPAm) - acrylic acid (AAc) microparticles were covalently functionalized with amine containing dyes via arnidation of carboxylic groups present in the microparticles. The dyes act as affinity baits towards protein analytes in solution. NIPAm/AAc microparticles functionalized with acid black 48 (AB48) mixed with human urine, achieved close to one hundred percent capture and 100 percent extraction yield of the target antigen. In urine, microparticles sequestered and concentrated Lyme disease antigens 100 fold, compared to the absence of microparticles, achieving an immunoassay detection sensitivity of 700 pg/mL in 10 mL urine. Antigen present in a single infected tick could be readily detected following microparticle sequestration. Hydrogel microparticles functionalized with high affinity baits can dramatically increase the sensitivity of urinary antigen tests for infectious diseases such as Lyme disease. These findings justify controlled clinical studies evaluating the sensitivity and precision of Lyme antigen testing in urine.

  • 24.
    Downs, Mark E.A.
    et al.
    Cranfield Institute of Technology, UK.
    Warner, Philip J.
    Cranfield Institute of Technology, UK.
    Turner, Anthony
    Cranfield University, UK.
    Fothergill, John C.
    University of Leicester, UK.
    Optical and electrochemical detection of DNA1988In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 9, no 1, p. 66-70Article in journal (Refereed)
    Abstract [en]

    There is a growing demand for the production of a DNA biosensor with applications in medicine, the food industry, agriculture, veterinary science and environmental science. In this paper we describe methods for the optical and electrochemical detection of DNA using the enzyme horseradish peroxidase (EC 1.11.1.7) and glucose oxidase (EC 1.1.3.4). We have used bis-methylacridinium nitrate and luminol for the optical detection of DNA using a purpose built, inexpensive luminometer. Using this system detection limits of 10−11g of plasmid DNA have been observed. Electrochemical detection of DNA was carried out by the use of a fluoride ion selective electrode and stripping voltametry. DNA was detected down to 1 (10−9 − 10−10g of DNA by the enzymatic release of halogen ions from organohalogen compounds.

  • 25.
    Duan, Xiaodong
    et al.
    Department of Chemical Engineering, McMaster University, Hamilton, Ont., Canada.
    McLaughlin, Christopher
    Department of Ophthalmology, University of Ottawa, Ottawa, Ont., Canada.
    Griffith, May
    Department of Ophthalmology, University of Ottawa, Ottawa, Ont., Canada.
    Sheardown, Heather
    Department of Chemical Engineering, McMaster University, Hamilton, Ont., Canada.
    Biofunctionalization of collagen for improved biological response: Scaffolds for corneal tissue engineering2007In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 28, no 1, p. 78-88Article in journal (Refereed)
    Abstract [en]

    Residual dendrimer amine groups were modified with incorporate COOH group containing biomolecules such as cell adhesion peptides into collagen scaffolds. YIGSR, as a model cell adhesion peptide, was incorporated into both the bulk structure of the gels and onto the gel surface. The effects of the peptide modified collagen gets on corneal epithelial cell behavior were examined with an aim of improving the potential of these materials as tissue-engineering scaffolds. YIGSR was first chemically attached to dendrimers and the YIGSR attached dendrimers were then used as collagen crosslinkers, incorporating the peptide into the bulk structure of the collagen gels. YIGSR was also attached to the surface of dendrimer crosslinked collagen gels through reaction with excess amine groups. The YIGSR modified dendrimers were characterized by H-NMR and MALDI mass spectra. The amount of YIGSR incorporated into collagen gels was determined by (125)1 radiolabelling at maximum to be 3.1-3.4 x 10(-2)mg/mg collagen when reacted with the bulk and 88.9-95.6 mu g/cm(2) when attached to the surface. The amount of YIGSR could be tuned by varying the amount of peptide reacted with the dendrimer or the amount of modified dendrimer used in the crosslinking reaction. It was found that YIGSR incorporation into the bulk and YIGSR modification of surface promoted the adhesion and proliferation of human corneal epithelial cells as well as neurite extension from dorsal root ganglia. (c) 2006 Elsevier Ltd. All rights reserved.

  • 26.
    Edlund, Ulrica
    et al.
    KTH, Superseded Departments, Polymer Technology.
    Albertsson, Ann-Christine
    KTH, Superseded Departments, Polymer Technology.
    Singh, K
    Fogelberg, I
    Lundgren, O
    Sterilization, storage stability and in vivo biocompatibility of poly(trimethylene carbonate)/poly(adipic anhydride) blends2000In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 21, no 9, p. 945-955Article in journal (Refereed)
    Abstract [en]

    Biodegradable blends of poly(trimethylene carbonate) (PTMC) and poly(adipic anhydride) (PAA) have been proven to be strong candidates for controlled drug delivery polymers in vitro. We now report on the stability, sterilizability and in vivo local tissue response of these matrices. Blend matrices were sterilized by beta-radiation or ethylene oxide gas treatment, stored at different times and temperatures, and analyzed for changes in physicochemical properties. Moisture uptake at different relative humidities and storage times was determined. Sterilization procedures induced hydrolysis of the matrices. Ethylene oxide gas sterilization had a significantly more marked effect upon the matrix properties than radiation treatment. The onset of degradation was reflected in a decrease of crystallinity and molecular weight along with a change of blend composition. A similar onset of matrix degradation was observed upon storage in air. The physicochemical properties of the blends were well preserved upon storage under argon atmosphere. Biocompatibility of PTMC/PAA implants was assessed in the anterior chamber of rabbits eyes for 1 month. At selected post-operative time points, aqueous humor was analyzed for white blood cells and the corneal thickness was measured. The results suggest good biocompatability of PTMC-rich matrices, whereas fast eroding PAA-rich matrices caused inflammatory responses, due to a burst release of degradation products.

  • 27. Ekstrand-Hammarstrom, Barbro
    et al.
    Hong, Jaan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Davoodpour, Padideh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Sandholm, Kerstin
    Ekdahl, Kristina N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Bucht, Anders
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 51, p. 58-68Article in journal (Refereed)
    Abstract [en]

    There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity.

  • 28. Ekstrand-Hammarström, Barbro
    et al.
    Hong, Jaan
    Davoodpour, Padideh
    Sandholm, Kerstin
    Ekdahl, Kristina N.
    Bucht, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Nilsson, Bo
    TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 51, p. 58-68Article in journal (Refereed)
    Abstract [en]

    There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity. 

  • 29.
    Ekstrand-Hammarström, Barbro
    et al.
    Swedish Def Res Agcy, Linköping.
    Hong, Jaan
    Uppsala University.
    Davoodpour, Padideh
    Uppsala University.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Bucht, Anders
    Umeå University.
    Nilsson, Bo
    Uppsala University.
    TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 51, p. 58-68Article in journal (Refereed)
    Abstract [en]

    There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity. (C) 2015 Elsevier Ltd. All rights reserved.

  • 30. Elgali, Ibrahim
    et al.
    Igawa, Kazuyo
    Palmquist, Anders
    Lenneras, Maria
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Choi, Sungjin
    Chung, Ung-Il
    Omar, Omar
    Thomsen, Peter
    Molecular and structural patterns of bone regeneration in surgically created defects containing bone substitutes2014In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, no 10, p. 3229-3242Article in journal (Refereed)
    Abstract [en]

    Several biomaterials have been introduced for bone augmentation. However, information is lacking about the mechanisms of bone regeneration and/or integration of these materials in the recipient bone. This study aimed to determine the molecular and structural events in bone defects after augmentation with synthetic tetrapod-shaped calcium phosphate (Tetrabone; TetraB) compared with natural deproteinized bovine bone (DBB). Defects were created in the epiphyses of rat femurs and filled with TetraB or DBB or left empty (Sham). After 3, 6, 14 and 28 d, samples were harvested for histology, histomorphometry, ultrastructure and gene expression analyses. At 3 d, higher expressions of bone formation (ALP and DC) and remodeling (CatK) genes were detected in TetraB compared with DBB and Sham. Downregulation of bone remodeling genes (TRAP and CatK) was detected in DBB as compared to Sham after 14 d. Histomorphometry at 6 and 14 d demonstrated greater bone contact with the granules in TetraB. At 28 d, a larger bone area per defect was found in TetraB. The present experiments show that a synthetic substitute, consisting of alpha-tricalcium and octacalcium phosphates, induces early osteogenic and osteoclastic activities and promotes bone formation in trabecular bone defects.

  • 31. Engberg, Anna E.
    et al.
    Nilsson, Per H.
    Huang, Shan
    Fromell, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Hamad, Osama A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Mollnes, Tom Eirik
    Rosengren-Holmberg, Jenny P.
    Sandholm, Kerstin
    Teramura, Yuji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nicholls, Ian A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ekdahl, Kristina N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 36, p. 55-65Article in journal (Refereed)
    Abstract [en]

    Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-gamma, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard.

  • 32.
    Engberg, Anna E.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Region Skåne.
    Nilsson, Per H.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Oslo Univ Hosp, Rikshosp, Norway;Univ Oslo, Norway.
    Huang, Shan
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Fromell, Karin
    Uppsala University.
    Hamad, Osama A.
    Uppsala University.
    Mollnes, Tom Eirik
    Univ Oslo, Norway;Univ Tromsö, Norway.
    Rosengren-Holmberg, Jenny P.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Swedish Natl Lab Forens Sci, Linköping.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Teramura, Yuji
    Uppsala University;Univ Tokyo, Japan.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 36, p. 55-65Article in journal (Refereed)
    Abstract [en]

    Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-gamma, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard. (C) 2014 Elsevier Ltd. All rights reserved.

  • 33. Engberg, Anna E.
    et al.
    Sandholm, Kerstin
    Bexborn, Fredrik
    Persson, Jenny
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Lindahl, Gunnar
    Ekdahl, Kristina Nilsson
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Inhibition of complement activation on a model biomaterial surface by streptococcal M protein-derived peptides2009In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 30, no 13, p. 2653-2659Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate a new approach to inhibit complement activation triggered by biomaterial surfaces in contact with blood. In order to inhibit complement activation initiated by the classical pathway (CP), we used streptococcal M protein-derived peptides that specifically bind human C4BP, an inhibitor of the CP. The peptides were used to coat polystyrene microtiter wells which served as a model biomaterial. The ability of coated peptides to bind C4BP and to attenuate complement activation via the CP (monitored as generation of fluid-phase C3a and binding of fragments of C3 and C4 to the surface) was investigated using diluted normal human serum, where complement activation by the AP is minimal, as well as serum from a patient lacking alternative pathway activation. Complement activation (all parameters) was significantly decreased in serum incubated in well surfaces coated with peptides. Total inhibition of complement activation was obtained at peptide coating concentrations as low as 1-5 microg/mL. Successful use of Streptococcus-derived peptides shows that it is feasible to control complement activation at a model biomaterial surface by capturing autologous complement regulatory molecules from plasma.

  • 34.
    Engberg, Anna E.
    et al.
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Sandholm, Kerstin
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Bexborn, Fredrik
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Persson, Jenny
    Lund University.
    Nilsson, Bo
    Uppsala University.
    Lindahl, Gunnar
    Lund University.
    Nilsson Ekdahl, Kristina
    University of Kalmar, School of Pure and Applied Natural Sciences. Uppsala University.
    Inhibition of complement activation on a model biomaterial surface by streptococcal M protein-derived peptides2009In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 30, no 13, p. 2653-2659Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate a new approach to inhibit complement activation triggered by biomaterial surfaces in contact with blood. In order to inhibit complement activation initiated by the classical pathway (CP), we used streptococcal M protein-derived peptides that specifically bind human C4BP, an inhibitor of the CP. The peptides were used to coat polystyrene microtiter wells which served as a model biomaterial. The ability of coated peptides to bind C4BP and to attenuate complement activation via the CP (monitored as generation of fluid-phase C3a and binding of fragments of C3 and C4 to the surface) was investigated using diluted normal human serum, where complement activation by the AP is minimal, as well as serum from a patient lacking alternative pathway activation. Complement activation (all parameters) was significantly decreased in serum incubated in well surfaces coated with peptides. Total inhibition of complement activation was obtained at peptide coating concentrations as low as 1-5 mu g/mL. Successful use of Streptococcus-derived peptides shows that it is feasible to control complement activation at a model biomaterial surface by capturing autologous complement regulatory molecules from plasma. (C) 2009 Elsevier Ltd. All rights reserved.

  • 35. Engelhardt, Eva-Maria
    et al.
    Micol, Lionel A.
    Houis, Stephanie
    Wurm, Florian M.
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry, Polymer Chemistry.
    Hubbell, Jeffrey A.
    Frey, Peter
    A collagen-poly(lactic acid-co-epsilon-caprolactone) hybrid scaffold for bladder tissue regeneration2011In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 32, no 16, p. 3969-3976Article in journal (Refereed)
    Abstract [en]

    Scaffold materials should favor cell attachment and proliferation, and provide designable 3D structures with appropriate mechanical strength. Collagen matrices have proven to be beneficial scaffolds for tissue regeneration. However, apart from small intestinal submucosa, they offer a limited mechanical strength even if crosslinking can enhance their mechanical properties. A more cell-friendly way to increase material strength is to combine synthetic polymer meshes with plastic compressed collagen gels. This work describes the potential of plastic compressed collagen poly(lactic acid-co-epsilon-caprolactone) (PLAC) hybrids as scaffolds for bladder tissue regeneration. Human bladder smooth muscle and urothelial cells were cultured on and inside collagen PLAC hybrids in vitro. Scaffolds were analyzed by electron microscopy, histology, immunohistochemistry, and AlamarBlue assay. Both cell types proliferated in and on the hybrid, forming dense cell layers on top after two weeks. Furthermore, hybrids were implanted subcutaneously in the backs of nude mice. Host cell infiltration, scaffold degradation, and the presence of the seeded bladder cells were analyzed. Hybrids showed a lower inflammatory reaction in vivo than PLAC meshes alone, and first signs of polymer degradation were visible at six months. Collagen PLAC hybrids have potential for bladder tissue regeneration, as they show efficient cell seeding, proliferation, and good mechanical properties.

  • 36.
    Eriksson, Cecilia
    et al.
    Göteborgs universitet.
    Lausmaa, Jukka
    SP Swedish National Testing and Research Institute, Boras.
    Nygren, Håkan
    Göteborgs universitet.
    Interactions between human whole blood and modified TiO2-surfaces: Influence of surface topography and oxide thickness on leukocyte adhesion and activation2001In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 22, no 14, p. 1987-1996Article in journal (Refereed)
    Abstract [en]

    An in vitro model (Nygren et al., J Lab Clin Med 129 (1997) 35-46) was used to investigate interactions between leukocytes and four modified TiO2-surfaces. Surface topography was measured using scanning electron microscopy and optical profilometry while Auger electron spectroscopy was used to determine surface composition and oxide thickness. The surfaces were either smooth or rough with either thin or thick oxides. All surfaces consisted of TiO2 covered by a carbonaceous layer. The surfaces were incubated with capillary blood for time periods of between 8 min and 32h. Immunofluorescence techniques together with computer aided image analysis and chemiluminescence technique were used to detect cell adhesion, expression of adhesion receptors and the zymosan-stimulated respiratory burst response. Leukocyte adhesion to the surfaces increased during the first hours of blood-material contact and then decreased. Polymorphonuclear granulocytes were the dominating leukocytes on all surfaces followed by monocytes. Cells adhering to rough surfaces had higher normalized expression of adhesive receptors than cells on smooth surfaces. Maximum respiratory burst response occurred earlier on the smooth than on the rough surfaces. In conclusion, topography had a greater impact than oxide thickness on most cellular reactions investigated, but the latter often had a dampening effect on the responses. (C) 2001 Elsevier Science Ltd. All rights reserved.

  • 37.
    Fagerholm, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Lagali, Neil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping.
    Ong, Jeb A.
    Maisonneuve Rosemont Hospital, Montreal, Canada .
    Merrett, Kimberley
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Ottawa Hospital Research Institute, Canada.
    Jackson, W. Bruce
    Ottawa Hospital Research Institute, Canada .
    Polarek, James W.
    FibroGen Inc, San Francisco, CA, USA.
    Suuronen, Erik J.
    University of Ottawa Heart Institute, Canada .
    Liu, Yuwen
    CooperVision Inc, Pleasanton, CA, USA.
    Brunette, Isabelle
    Maisonneuve Rosemont Hospital, Montreal, Canada .
    Griffith, May
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold2014In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, no 8, p. 2420-2427Article in journal (Refereed)
    Abstract [en]

    We developed cell-free implants, comprising carbodiimide crosslinked recombinant human collagen (RHC), to enable corneal regeneration by endogenous cell recruitment, to address the worldwide shortage of donor corneas. Patients were grafted with RHC implants. Over four years, the regenerated neo-corneas were stably integrated without rejection, without the long immunosuppression regime needed by donor cornea patients. There was no recruitment of inflammatory dendritic cells into the implant area, whereas, even with immunosuppression, donor cornea recipients showed dendritic cell migration into the central cornea and a rejection episode was observed. Regeneration as evidenced by continued nerve and stromal cell repopulation occurred over the four years to approximate the micro-architecture of healthy corneas. Histopathology of a regenerated, clear cornea from a regrafted patient showed normal corneal architecture. Donor human cornea grafted eyes had abnormally tortuous nerves and stromal cell death was found. Implanted patients had a 4-year average corrected visual acuity of 20/54 and gained more than 5 Snellen lines of vision on an eye chart. The visual acuity can be improved with more robust materials for better shape retention. Nevertheless, these RHC implants can achieve stable regeneration and therefore, represent a potentially safe alternative to donor organ transplantation.

  • 38. Feliu, Neus
    et al.
    Walter, Marie Valérie
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Coating Technology.
    Montañez, Maria I.
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Coating Technology.
    Kunzmann, Andrea
    Hult, Anders
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Coating Technology.
    Nyström, Andreas
    Malkoch, Michael
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Coating Technology.
    Fadeel, Bengt
    Stability and biocompatibility of a library of polyester dendrimers in comparison to polyamidoamine dendrimers2012In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 33, no 7, p. 1970-1981Article in journal (Refereed)
    Abstract [en]

    Dendrimers can be designed for several biomedical applications due to their well-defined structure, functionality and dimensions. The present study focused on the in vitro biocompatibility evaluation of a library of aliphatic polyester dendrimers based on 2,2-bis(methylol)propionic acid (bis-MPA) with an overall diameter of 0.5-2 nm. In addition, dendrimers with two different chemical surfaces (neutral with hydroxyl end group and anionic with carboxylic end group) and dendrons corresponding to the structural fragments of the dendrimers were evaluated. Commercial polyamidoamine dendrimers (PAMAM) with cationic (amine) or neutral (hydroxyl) end group were also included for comparison. Cell viability studies were conducted in human cervical cancer (HeLa) and acute monocytic leukemia cells (THP.1) differentiated into macrophage-like cells as well as in primary human monocyte-derived macrophages. Excellent biocompatibility was observed for the entire hydroxyl functional bis-MPA dendrimer library, whereas the cationic, but not the neutral PAMAM exerted dose-dependent cytotoxicity in cell lines and primary macrophages. Studies to evaluate material stability as a function of pH, temperature, and time, demonstrated that the stability of the 4th generation hydroxyl functional bis-MPA dendrimer increased at acidic pH. Taken together, bis-MPA dendrimers are degradable and non-cytotoxic to human cell lines and primary cells.

  • 39. Gallud, Audrey
    et al.
    Bondarenko, Olesja
    Feliu, Neus
    Kupferschmidt, Natalia
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Atluri, Rambabu
    Garcia-Bennett, Alfonso
    Fadeel, Bengt
    Macrophage activation status determines the internalization of mesoporous silica particles of different sizes: Exploring the role of different pattern recognition receptors2017In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 121, p. 28-40Article in journal (Refereed)
    Abstract [en]

    Mesoporous silica-based particles are promising candidates for biomedical applications. Here, we address the importance of macrophage activation status for internalization of AMS6 (approx. 200 nm in diameter) versus AMS8 (approx. 2 mu m) mesoporous silica particles and the role of different phagocytosis receptors for particle uptake. To this end, FITC-conjugated silica particles were used. AMS8 were found to be non-cytotoxic both for M-CSF-stimulated (anti-inflammatory) and GM-CSF-stimulated (pro-inflammatory) macrophages, whereas AMS6 exhibited cytotoxicity towards M-CSF-stimulated, but not GMCSF-stimulated macrophages; this toxicity was, however, mitigated in the presence of serum. AMS8 triggered the secretion of pro-inflammatory cytokines in M-CSF-activated cells. Class A scavenger receptor (SR-A) expression was noted in both M-CSF and GM-CSF-stimulated macrophages, although the expression was higher in the former case, and gene silencing of SR-A resulted in a decreased uptake of AMS6 in the absence of serum. GM-CSF-stimulated macrophages expressed higher levels of the mannose receptor CD206 compared to M-CSF-stimulated cells, and uptake of AMS6, but not AMS8, was reduced following the downregulation of CD206 in GM-CSF-stimulated cells; particle uptake was also suppressed by mannan, a competitive ligand. These studies demonstrate that macrophage activation status is an important determinant of particle uptake and provide evidence for a role of different macrophage receptors for cell uptake of silica particles.

  • 40. Georgiou, Melanie
    et al.
    Golding, Jon P.
    Loughlin, Alison J.
    Kingham, Paul J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Phillips, James B.
    Engineered neural tissue with aligned, differentiated adipose-derived stem cells promotes peripheral nerve regeneration across a critical sized defect in rat sciatic nerve2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 37, p. 242-251Article in journal (Refereed)
    Abstract [en]

    Adipose-derived stem cells were isolated from rats and differentiated to a Schwann cell-like phenotype in vitro. The differentiated cells (dADSCs) underwent self-alignment in a tethered type-1 collagen gel, followed by stabilisation to generate engineered neural tissue (EngNT-dADSC). The pro-regenerative phenotype of dADSCs was enhanced by this process, and the columns of aligned dADSCs in the aligned collagen matrix supported and guided neurite extension in vitro. EngNT-dADSC sheets were rolled to form peripheral nerve repair constructs that were implanted within NeuraWrap conduits to bridge a 15 mm gap in rat sciatic nerve. After 8 weeks regeneration was assessed using immunofluorescence imaging and transmission electron microscopy and compared to empty conduit and nerve graft controls. The proportion of axons detected in the distal stump was 3.5 fold greater in constructs containing EngNT-dADSC than empty tube controls. Our novel combination of technologies that can organise autologous therapeutic cells-within an artificial tissue construct provides a promising new cellular biomaterial for peripheral nerve repair. 

  • 41.
    Goransson, A.
    et al.
    Göransson, A., Department of Biomaterial Science, Institute of Surgical Science, Göteborg University, Göteborg 40530, Sweden, Department of Prosthetic Dentistry/Dental Material Science, Box 412, Göteborg University, Göteborg 40530, Sweden.
    Jansson, Eva
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology.
    Tengvall, Pentti
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    Wennerberg, A.
    Department of Biomaterial Science, Institute of Surgical Science, Göteborg University, Göteborg 40530, Sweden, Department of Prosthetic Dentistry/Dental Material Science, Box 412, Göteborg University, Göteborg 40530, Sweden.
    Bone formation after 4 weeks around blood-plasma-modified titanium implants with varying surface topographies: An in vivo study2003In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 24, no 2, p. 197-205Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to investigate and compare the stability and bone ingrowth capacity to screw-shaped titanium implants with five different surface treatments. The implants were: (1) standard turned with a thin blood plasma coat (TP), (2) NaOH-etched dito with pore size 0.2-0.3µm (E), (3) NaOH-etched with pore size 0.2-0.3µm and a thin blood plasma coat (EP), (4) electrochemically oxidised with pore size 1-2µm (O), (5) electrochemically oxidised with pore size 1-2µm and a thin blood plasma coat (OP). A total of 66 implants were divided into the above-described five groups and inserted for 4 weeks into tibia and femur of 11 rabbits. The implants were evaluated by resonance frequency (RF) measurements at the time of insertion and removal, and analysed histomorphometrically at removal. The RF measurements showed that the implant stability was lower in soft bone compared to dense and increased with time. No significant differences were observed between the different surface modifications. The histomorphometric analysis revealed no statistically significant differences between the implants regarding bone-to-metal contact (BMC) and bone area inside the threads (BA). The above results indicate that thin blood plasma-coated and non-coated screw-shaped titanium implants with turned, NaOH-etched and electrochemically etched surface profiles integrate similarly to bone at 1 month of implantation. © 2002 Elsevier Science Ltd. All rights reserved.

  • 42. Hannink, Gerjon
    et al.
    Aspenberg, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Schreurs, B Willem
    Buma, Pieter
    Development of a large titanium bone chamber to study in vivo bone ingrowth2006In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 27, no 9, p. 1810-1816Article in journal (Refereed)
    Abstract [en]

    In the bone conduction chamber (BCC) various materials and factors have been tested for their effect on bone graft incorporation and bone healing. However, biomaterials often have to be crushed to fit in this small chamber. Since cellular responses to biomaterials are influenced by the size and shape of particles, research concerning the evaluation of biomaterials is limited by the dimensions of this bone chamber. We enlarged and modified the BCC in order to be able to investigate the in vivo influences of biomaterials, growth factors and bone graft processing on tissue and bone ingrowth. Seven goats received four bone chambers each, three modified models and a BCC. The first model (BCC+) had two ingrowth openings, similar to that of the BCC. The second model had two round ingrowth openings (ROU). The third model had a open bottom for bone ingrowth (BOT). After 12 weeks, bone ingrowth distances were measured on histological sections and using μCT. Bone ingrowth was significantly higher (p=0.009 and 0.008) in the ROU compared to the BCC+ and the BOT, respectively. Similar results were found using μCT. The ROU model performed most similar to the BCC (gold standard) and is considered to be a promising new tool in biomaterials research. © 2005 Elsevier Ltd. All rights reserved.

  • 43.
    Hansson, Kenny
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Tosatti, Samuele
    Isaksson, Joakim
    Linköping University, The Institute of Technology. Linköping University, Department of Science and Technology.
    Wetterö, Jonas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Textor, Marcus
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Tengvall, Pentti
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics.
    Whole blood coagulation on protein adsorption-resistant PEG and peptide functionalised PEG-coated titanium surfaces2005In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 26, no 8, p. 861-872Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate whole blood coagulation on low blood plasma protein adsorbing surfaces. For this purpose, the polycationic graft copolymer poly(L-lysine)-g-poly(ethylene glycol) (PLL-g-PEG), PLL-g-PEG grafted with a cell adhesive peptide containing the amino acid sequence -Arg-Gly-Asp- (RGD), and PLL-g-PEG with a control peptide -Arg-Asp-Gly- (RDG) were adsorbed onto titanium (oxide), forming stable monomolecular adlayers through electrostatic attraction. Free oscillation rheometry and complementary techniques were used to measure the coagulation time (CT) and other interactions of the surfaces with native whole blood, recalcified platelet-rich plasma (PRP), and recalcified citrated platelet-free plasma (PFP). The results show that the uncoated titanium surfaces (reference) activated platelets and quickly triggered the coagulation cascade via the intrinsic pathway, whereas the PLL-g-PEG surfaces displayed a prolonged CT, approximately 2-3 times longer compared to uncoated titanium. We hypothesise that blood coagulates outside the vascular system independent of low protein adsorption to or activation by surfaces, due to the absence of an active down-regulation of procoagulative processes by the vascular endothelium.

  • 44.
    Hong, Jaan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology and Transfusion Medicine. Klinisk immunologi.
    Nilsson Ekdahl, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology and Transfusion Medicine.
    Reynolds, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology and Transfusion Medicine.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology and Transfusion Medicine.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology and Transfusion Medicine.
    A new in vitro model to study interaction between whole blood and biomaterials. Studies of platelet and coagulation activation and the effect of aspirin1999In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 20, no 7, p. 603-611Article in journal (Refereed)
    Abstract [en]

    We have developed a versatile in vitro chamber model with a double purpose: first, to be able to study mechanisms of bio- incompatibility, and, second, to test biomaterials at all levels of interactions, in whole blood. The use of biomaterials in the form of microscope slides as walls in the chamber makes it possible to analyse both the biomaterial surface with regard to protein and cell binding, as well as the molecular events taking place in the fluid. Incubation of blood in the chamber, for 60 min at 37°C resulted in the rapid binding of complement and coagulation proteins and of leukocytes and platelets to polyvinylchloride (PVC) slides. The cells formed a layer which more or less covered the underlying surface. Unlike complement activation, as reflected by soluble C3a and C5b-9, the thrombin—antithrombin formation was completely nullified in cell-depleted plasma. Despite the fact that throm- bin—antithrombin generation was also negligible in platelet-rich plasma, inhibition of platelet aggregation on the material surface with aspirin resulted in suppressed generation of thrombin—antithrombin complexes. Taken together, the coagulation activation in the chamber was dependent on the presence of blood cells which suggests that bound/aggregated platelets initiate a sequence of events involving leukocytes that results in coagulation activation. 

  • 45. Huang, Shan
    et al.
    Engberg, Anna E.
    Linnaeus Univ, Ctr Biomat Chem, Kalmar, Sweden.;Univ & Reg Labs Reg, Dept Clin Chem, Skane, Sweden..
    Jonsson, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sandholm, Kerstin
    Nicholls, Ian A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Mollnes, Tom Eirik
    Natl Hosp Norway, Oslo Univ Hosp, Dept Immunol, Oslo, Norway.;Univ Oslo, KG Jebsen ICR, N-0316 Oslo, Norway.;Nordland Hosp, Res Lab, Bodo, Norway.;Univ Tromso, Fac Hlth Sci, N-9001 Tromso, Norway.;Norwegian Univ Sci & Technol, Ctr Mol Inflammat Res, N-7034 Trondheim, Norway..
    Fromell, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ekdahl, Kristina N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood2016In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 77, p. 111-119Article in journal (Refereed)
    Abstract [en]

    Background: Inappropriate and uncontrolled activation of the cascade systems in the blood is a driving force in adverse inflammatory and thrombotic reactions elicited by biomaterials, but limited data are available on the activation of the contact system by polymers and the present study was undertaken to investigate these mechanisms in established models. Methods: Polymer particles were incubated in (1) EDTA-plasma (10 mM) to monitor the adsorption of 20 selected proteins; (2) lepirudin-anticoagulated plasma to evaluate contact system activation, monitored by the formation of complexes between the generated proteases factor[F]XIIa, FXIa and kallikrein and the serpins C1-inhibitor [C1INH] and antithrombin [AT]; (3) lepirudin-anticoagulated whole blood to determine cytokine release. Results: Strong negative correlations were found between 10 cytokines and the ratio of deposited FXII/C1INH, generated FXIIa-C1INH complexes, and kallikrein-C1INH complexes. Formation of FXIIa-C1INH complexes correlated negatively with the amount of C3a and positively with deposited IgG. Conclusions: A reciprocal relationship was found between activation of the contact system and the complement system induced by the polymers studied here. The ratios of FXII/C1INH or C4/C4BP, adsorbed from EDTA-plasma are useful surrogate markers for cytokine release and inflammatory response to materials intended for blood contact.

  • 46.
    Huang, Shan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Engberg, Anna E.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. University and Regional Laboratories Region Skåne.
    Jonsson, Nina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Nicholls, Ian A.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Mollnes, Tom Eirik
    Oslo University Hospital Rikshopsitalet, Norway;University of Oslo, Norway;Nordland Hospital, Norway; University of Tromsø, Norway;Norwegian University of Science and Technology, Norway.
    Fromell, Karin
    Uppsala University.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Reciprocal relationship between contact and complement system activation on artificial polymers exposed to whole human blood.2016In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 77, p. 111-119Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Inappropriate and uncontrolled activation of the cascade systems in the blood is a driving force in adverse inflammatory and thrombotic reactions elicited by biomaterials, but limited data are available on the activation of the contact system by polymers and the present study was undertaken to investigate these mechanisms in established models.

    METHODS: Polymer particles were incubated in (1) EDTA-plasma (10 mM) to monitor the adsorption of 20 selected proteins; (2) lepirudin-anticoagulated plasma to evaluate contact system activation, monitored by the formation of complexes between the generated proteases factor[F]XIIa, FXIa and kallikrein and the serpins C1-inhibitor [C1INH] and antithrombin [AT]; (3) lepirudin-anticoagulated whole blood to determine cytokine release.

    RESULTS: Strong negative correlations were found between 10 cytokines and the ratio of deposited FXII/C1INH, generated FXIIa-C1INH complexes, and kallikrein-C1INH complexes. Formation of FXIIa-C1INH complexes correlated negatively with the amount of C3a and positively with deposited IgG.

    CONCLUSIONS: A reciprocal relationship was found between activation of the contact system and the complement system induced by the polymers studied here. The ratios of FXII/C1INH or C4/C4BP, adsorbed from EDTA-plasma are useful surrogate markers for cytokine release and inflammatory response to materials intended for blood contact.

  • 47.
    Izquierdo-Barba, Isabel
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Inorganic and Structural Chemistry.
    Kupferschmidt, Natalia
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Inorganic and Structural Chemistry.
    Terasaki, Osamu
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Schmidtchen, Artur
    Malmsten, Martin
    Vallet-Regí, Maria
    Incorporation of antimicrobial compounds in mesoporous silica film monolith2009In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 30, no 29, p. 5729-5736Article in journal (Refereed)
    Abstract [en]

    : Incorporation of the antimicrobial peptide LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES), as well as low molecular weight antimicrobial chlorhexidine, into mesoporous silica was obtained using an EISA one-pot synthesis method. FTIR confirmed efficient encapsulation of both LL-37 and chlorhexidine into mesoporous silica, while XRD and TEM showed that antimicrobial agent incorporation can be achieved without greatly affecting the structure of the mesoporous silica. The modified mesoporous silica released LL-37 and chlorhexidine slowly, reaching maximum release after about 200 h. The release rate could also be controlled through incorporation of SH groups in the pore walls, adding to pore hydrophobicity and reducing the release rate by about 50% compared to the unmodified mesoporous silica. Mesoporous silica containing either LL-37 or chlorhexidine displayed potent bactericidal properties against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. While chlorhexidine-loaded mesoporous silica displayed an accompanying high toxicity, as judged from hemolysis, LDH release, and MTT assay, the corresponding material containing LL-37 showed very low toxicity by all these assays, comparable to that observed for mesoporous silica in the absence of antibacterial drug, as well as to the negative controls in the respective assays. Mesoporous silica containing LL-37 therefore holds potential as an implantable material or a surface coating for such materials, as it combines potent bactericidal action with low toxicity, important features for controlling implant-related infections, e.g., for multi-resistant pathogens or for cases where access to the infection site of systemically administered antibiotics is limited due to collagen capsule formation or other factors.

     

  • 48. Izquierdo-Barba, Isabel
    et al.
    Vallet-Regí, María
    Kupferschmidt, Natalia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Terasaki, Osamu
    Schmidtchen, Artur
    Malmsten, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Incorporation of antimicrobial compounds in mesoporous silica film monolith2009In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 30, no 29, p. 5729-5736Article in journal (Refereed)
    Abstract [en]

    Incorporation of the antimicrobial peptide LL-37 (LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES), as well as low molecular weight antimicrobial chlorhexidine, into mesoporous silica was obtained using an EISA one-pot synthesis method. FTIR confirmed efficient encapsulation of both LL-37 and chlorhexidine into mesoporous silica, while XRD and TEM showed that antimicrobial agent incorporation can be achieved without greatly affecting the structure of the mesoporous silica. The modified mesoporous silica released LL-37 and chlorhexidine slowly, reaching maximum release after about 200 h. The release rate could also be controlled through incorporation of SH groups in the pore walls, adding to pore hydrophobicity and reducing the release rate by about 50% compared to the unmodified mesoporous silica. Mesoporous silica containing either LL-37 or chlorhexidine displayed potent bactericidal properties against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. While chlorhexidine-loaded mesoporous silica displayed an accompanying high toxicity, as judged from hemolysis, LDH release, and MTT assay, the corresponding material containing LL-37 showed very low toxicity by all these assays, comparable to that observed for mesoporous silica in the absence of antibacterial drug, as well as to the negative controls in the respective assays. Mesoporous silica containing LL-37 therefore holds potential as an implantable material or a surface coating for such materials, as it combines potent bactericidal action with low toxicity, important features for controlling implant-related infections, e.g., for multi-resistant pathogens or for cases where access to the infection site of systemically administered antibiotics is limited due to collagen capsule formation or other factors.

  • 49. Jansson, E.
    et al.
    Kalltorp, M.
    Källtorp, M., Institute of Anatomy and Cell Biology, Göteborg University, Box 420, SE-405 30 Göteborg, Sweden.
    Thomsen, P.
    Institute of Anatomy and Cell Biology, Göteborg University, Box 420, SE-405 30 Göteborg, Sweden.
    Tengvall, Pentti
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    Ex vivo PMA-induced respiratory burst and TNF-a secretion elicited from inflammatory cells on machined and porous blood plasma clot-coated titanium2002In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 23, no 13, p. 2803-2815Article in journal (Refereed)
    Abstract [en]

    The release of inflammatory mediators around implants and normal wounds may differ due to the presence of the solid surface. In this study, machined and sub-micron porous titanium implants with and without a 100nm thick blood plasma clot were inserted subcutaneously in rat for 3 or 24h. The cell recruitment to the interfaces, in vivo secretion of TNF-a and the ex vivo PMA-induced production of reactive oxygen species were subsequently investigated. The thin plasma clot coating gave rise to an increased ex vivo PMA-stimulated oxygen radical production by implant-associated cells at both implantation times, and an increased cell recruitment at 24h. The total TNF-a secretion was highest at sham sites and plasma clot-coated porous titanium at 24h. After 24h, the cell-type pattern in the exudate around the porous plasma-coated implant was more similar to that found at sham sites than that adjacent to the non-coated implants. No differences were observed between the machined Ti and the machined sub-micron porous Ti. © 2002 Elsevier Science Ltd. All rights reserved.

  • 50.
    Jansson, Eva
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology.
    Tengvall, Pentti
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    In vitro preparation and ellipsometric characterization of thin blood plasma clot films on silicon2001In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 22, no 13, p. 1803-1808Article in journal (Refereed)
    Abstract [en]

    The wound-healing process around implants differs from that of a normal healing without the inserted material. In this work, the composition of a natural wound surface was mimicked through clotting of a thin human blood plasma film with approximate ellipsometric thickness of 100nm onto differently pretreated silicon surfaces. Their stability was investigated by incubations in sodium dodecyl sulphate (SDS) solutions. The enzymatic clot degradation was induced through addition of human tissue plasminogen activator (t-PA) to the plasma and the surface protein remnants after the degradation were analyzed with polyclonal antibodies. The results show that the plasma films were not SDS resistant on hydrophilic silicon. However, stability was obtained after preparation on hydrophobic silicon or when albumin or fibrinogen was immobilized to silicon before the plasma incubations. Different surfaces bound different polyclonal antibodies after the clot film degradation. The methods indicate a simple means to improve or reestablish a normal tissue inflammatory response around biomaterials. Copyright © 2001 Elsevier Science Ltd.

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