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  • 1.
    Alarcon, Emilio I
    et al.
    University of Ottawa.
    Udekwu, Klas
    Karolinska Institute.
    Skog, Mårten
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Pacioni, NataliL
    University of Ottawa.
    Stamplecoskie, Kevin G
    University of Ottawa.
    Gonzalez-Bejar, Maria
    University of Ottawa.
    Polisetti, Naresh
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Wickham, Abeni
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Richter-Dahlfors, Agneta
    Karolinska Institute.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmiatrik. Linköpings universitet, Hälsouniversitetet.
    Scaiano, Juan C
    University of Ottawa.
    The biocompatibility and antibacterial properties of collagen-stabilized, photochemically prepared silver nanoparticles2012Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 33, nr 19, s. 4947-4956Artikel i tidskrift (Refereegranskat)
    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.

  • 2.
    Arvidsson, Sara
    et al.
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik.
    Askendal, Agneta
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik.
    Tengvall, Pentti
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik.
    Blood plasma contact activation on silicon titanium and aluminium2007Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 28, s. 1346-1354Artikel i tidskrift (Refereegranskat)
    Abstract [en]

       

  • 3.
    Bayat, Narges
    et al.
    Stockholm University, Sweden.
    Lopes, Viviana
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Schoelermann, Julia
    University of Bergen, Norway.
    Jensen, Lasse
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Cristobal, Susana
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Stockholm University, Sweden; University of Basque Country, Spain.
    Vascular toxicity of ultra-small TiO2 nanoparticles and single walled carbon nanotubes in vitro and in vivo2015Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 63Artikel i tidskrift (Refereegranskat)
    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.

  • 4.
    Benesch, Johan
    et al.
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Tengvall, Pentti
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik.
    Blood protein adsorption onto chitosan2002Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 23, nr 12, s. 2561-2568Artikel i tidskrift (Refereegranskat)
    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.

  • 5.
    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.2013Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 34, nr 5, s. 1546-1561Artikel i tidskrift (Refereegranskat)
    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.

  • 6.
    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 B2011Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 32, nr 1, s. 295-305Artikel i tidskrift (Refereegranskat)
    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.

  • 7.
    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 DNA1988Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 9, nr 1, s. 66-70Artikel i tidskrift (Refereegranskat)
    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.

  • 8.
    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 engineering2007Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 28, nr 1, s. 78-88Artikel i tidskrift (Refereegranskat)
    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.

  • 9.
    Fagerholm, Per
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM.
    Ong, Jeb A.
    Maisonneuve Rosemont Hospital, Montreal, Canada .
    Merrett, Kimberley
    Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM. 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
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold2014Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, nr 8, s. 2420-2427Artikel i tidskrift (Refereegranskat)
    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.

  • 10.
    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
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Tengvall, Pentti
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik.
    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 study2003Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 24, nr 2, s. 197-205Artikel i tidskrift (Refereegranskat)
    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.

  • 11. Hannink, Gerjon
    et al.
    Aspenberg, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Ortopedi och Idrottsmedicin. Östergötlands Läns Landsting, Ortopedicentrum, Ortopedkliniken Linköping.
    Schreurs, B Willem
    Buma, Pieter
    Development of a large titanium bone chamber to study in vivo bone ingrowth2006Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 27, nr 9, s. 1810-1816Artikel i tidskrift (Refereegranskat)
    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.

  • 12.
    Hansson, Kenny
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Tosatti, Samuele
    Isaksson, Joakim
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för teknik och naturvetenskap.
    Wetterö, Jonas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi.
    Textor, Marcus
    Lindahl, Tomas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk kemi.
    Tengvall, Pentti
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik.
    Whole blood coagulation on protein adsorption-resistant PEG and peptide functionalised PEG-coated titanium surfaces2005Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 26, nr 8, s. 861-872Artikel i tidskrift (Refereegranskat)
    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.

  • 13. 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
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik.
    Ex vivo PMA-induced respiratory burst and TNF-a secretion elicited from inflammatory cells on machined and porous blood plasma clot-coated titanium2002Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 23, nr 13, s. 2803-2815Artikel i tidskrift (Refereegranskat)
    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.

  • 14.
    Jansson, Eva
    et al.
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi.
    Tengvall, Pentti
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik.
    In vitro preparation and ellipsometric characterization of thin blood plasma clot films on silicon2001Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 22, nr 13, s. 1803-1808Artikel i tidskrift (Refereegranskat)
    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.

  • 15.
    Klenkler, BJ
    et al.
    Department of Chemical Engineering, McMaster University, Hamilton, ON, Canada.
    Griffith, May
    Department of Ophthalmology, University of Ottawa, Ottawa, ON, Canada.
    Becerril, C
    Department of Ophthalmology, University of Ottawa, Ottawa, ON, Canada.
    West-Mays, JA
    Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
    Sheardown, H
    Department of Chemical Engineering, McMaster University, Hamilton, ON, Canada.
    EGF-grafted PDMS surfaces in artificial cornea applications2005Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 26, nr 35, s. 7286-7296Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Lack of epithelial cell coverage has remained a persistent problem in the design of an artificial cornea. In this work, polydimethylsiloxane (PDMS) surfaces were modified with epidermal growth factor (EGF) to improve the growth of corneal epithelial cells. The EGF was covalently tethered to PDMS substrates aminated by plasma polymerization of allylamine via a homobifunctional polyethylene glycol (PEG) spacer. Surface modification was confirmed by contact angle and X-ray photoelectron spectroscopy measurements. By varying the ratio of EGF to PEG from 1:50 to 1:5, EGF amounts from 40 to 90ng/cm(2) could be bound, as determined by surface plasmon resonance (SPR) and I-125 radiolabelling. Human corneal epithelial cells on the various modified surfaces were cultured both in the presence and absence of EGF in the culture medium to determine the effect of covalently bound EGF on the cells. The results demonstrated that covalently bound EGF on the surfaces is active with respect to promoting epithelial cell coverage. This was significant when compared to unmodified controls. (c) 2005 Elsevier Ltd. All rights reserved.

  • 16.
    Li, F
    et al.
    University of Ottawa Eye Institute and National Research Council, Ottawa, Canada.
    Griffith, M
    University of Ottawa Eye Institute, Ottawa, Canada.
    Li, Z
    National Research Council, Ottawa, Canada.
    Tanodekaew, S
    National Research Council, Ottawa, Canada and National Science and Technology Development Center, Pathumthani, Thailand.
    Sheardown, H
    Department of Chemical Engineering, McMaster University, Hamilton, Canada.
    Hakim, M
    University of Ottawa Eye Institute and National Research Council, Ottawa, Canada.
    Carlsson, DJ
    University of Ottawa Eye Institute and National Research Council, Ottawa, Canada.
    Recruitment of multiple cell lines by collagen-synthetic copolymer matrices in corneal regeneration2005Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 26, nr 16, s. 3093-3104Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Collagen hydrogel matrices with high optical clarity have been developed from collagen 1, cross-linked with a copolymer based on N-isopropylacrylamide, acrylic acid and acryloxysuccinimide. The controlled reaction of collagen amine groups with this copolymer under neutral pH and aqueous conditions gave robust, optically clear hydrogels and prevented the excessive collagen fibrillogenesis that can lead to collagen opacity. These sterile, non-cytotoxic hydrogels allowed epithelial cell overgrowth and both stromal cell and nerve neurite ingrowth from the host tissue. This regenerative ability appeared to result from the high glucose permeability, nanoporosity and the presence of cell adhesion factors, RGD in collagen and the laminin pentapeptide, YIGSR, grafted onto the copolymer. Under physiological conditions, optical clarity superior to the human cornea and tensile performance adequate for suturing were obtained from some formulations. (C) 2004 Elsevier Ltd. All rights reserved.

  • 17.
    Liu, Lei
    et al.
    Department of Ophthalmology, Institute of Medical Science, Foresterhill, University of Aberdeen, Aberdeen, Scotland, UK.
    Kuffova, Lucia
    Department of Ophthalmology, Institute of Medical Science, Foresterhill, University of Aberdeen, Aberdeen, Scotland, UK.
    Griffith, May
    University of Ottawa Eye Institute, Ottawa Health Research Institute-Vision Centre, Ottawa, ON, Canada.
    Dang, Zexu
    Department of Ophthalmology, Institute of Medical Science, Foresterhill, University of Aberdeen, Aberdeen, Scotland, UK.
    Muckersie, Elizabeth
    Department of Ophthalmology, Institute of Medical Science, Foresterhill, University of Aberdeen, Aberdeen, Scotland, UK.
    Liu, Yuwen
    National Research Council Canada, Ottawa, ON, Canada.
    McLaughlin, Christopher R.
    University of Ottawa Eye Institute, Ottawa Health Research Institute-Vision Centre, Ottawa, ON, Canada.
    Forrester, John V.
    Department of Ophthalmology, Institute of Medical Science, Foresterhill, University of Aberdeen, Aberdeen, Scotland, UK.
    Immunological responses in mice to full-thickness corneal grafts engineered from porcine collagen2007Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 28, nr 26, s. 3807-3814Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Tissue-engineered (TE) corneas were fabricated from porcine collagen cross-linked with 1-ethyl-3-(3-dimethyl aminoproplyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS), and were transplanted into BALB/c mice orthotopically using a full-thickness penetrating keratoplasty (PKP) procedure. The biocompatibility was evaluated by assessing both local and systemic immune responses. Myeloid cells including granulocytes and macrophages were the main infiltrating cells in recipient cornea and in retro-TE corneal membrane which developed 7-10 days post surgery. Sodium citrate was found to be effective in reducing fibrin accumulation in anterior chamber post grafting at early time points, but it did not prevent formation of the retro-TE corneal membrane. No significant T cell activation was observed in the submandibular draining lymph nodes (SMDLN) by flow cytometry. Anti-porcine type I collagen IgG antibodies were detected in the serum of grafted mice from 2 weeks post grafting and the concentration of antibodies increased with time. Overall, porcine collagen-EDC/NHS TE corneas were tolerated well in murine recipients, causing mainly a self-limiting local innate immune response and a low-grade humoral response with little evidence of sustained T cell activation. Retro-TE corneal membrane formation was the main complication and barrier to clarity.

  • 18.
    Liu, Wenguang
    et al.
    Deptartment of Cellular and Molecular Medicine University of Ottawa, Ottawa, Ontario, Canada.
    Merrett, Kimberley
    University of Ottawa Eye Institute, 501 Smyth Road, Ottawa, Ontario K1H8L6, Canada.
    Griffith, May
    Deptartment of Cellular and Molecular Medicine University of Ottawa, Ottawa, Ontario, Canada.
    Fagerholm, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US.
    Dravida, Subhadra
    Dravida.
    Heyne, Belinda
    Deptartment of Chemistry University of Ottawa, Ottawa, Ontario, Canada.
    Scaiano, Juan C.
    Deptartment of Chemistry University of Ottawa, Ottawa, Ontario, Canada.
    Watsky, Mitchell A.
    Deptartment of Physiology University of Tennessee Health Science Center, Memphis, TN, USA.
    Shinozaki, Naoshi
    Cornea Centre and Eye Bank Tokyo Dental College, Chiba, Japan.
    Lagali, Neil
    University of Ottawa Eye Institute, 501 Smyth Road, Ottawa, Ontario K1H8L6, Canada.
    Munger, Rejean
    University of Ottawa Eye Institute, 501 Smyth Road, Ottawa, Ontario K1H8L6, Canada.
    Li, Fengfu
    University of Ottawa Eye Institute, 501 Smyth Road, Ottawa, Ontario K1H8L6, Canada.
    Recombinant human collagen for tissue engineered corneal substitutes2008Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 29, nr 9, s. 1147-1158Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We successfully fabricated transparent, robust hydrogels as corneal substitutes from concentrated recombinant human type I and type III collagen solutions crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). White light transmission through these gels is comparable or superior to that of human corneas. Hydrogels from both type I and type III collagens supported in vitro epithelium and nerve over-growth. While both these biocompatible hydrogels have adequate tensile strength and elasticity for surgical manipulation, type III collagen hydrogels tended to be mechanically superior. Twelve-month post-implantation results of type I recombinant collagen-based corneal substitutes into mini-pigs showed retention of optical clarity, along with regeneration of corneal cells, nerves and tear film. For clinical use, implants based on fully characterized, recombinant human collagen eliminate the risk of pathogen transfer or xenogeneic immuno-responses posed by animal collagens. © 2007 Elsevier Ltd. All rights reserved.

  • 19.
    McLaughlin, CR
    et al.
    Univ Ottawa, Ottawa Hosp, Inst Eye, Ottawa, ON K1H 8L6 Canada.
    Carmen, AM
    Univ Miguel Hernandez, CSIC, Inst Neurociencias Alicante, Alacant 03550, Spain.
    Carmen, C
    Univ Miguel Hernandez, CSIC, Inst Neurociencias Alicante, Alacant 03550, Spain.
    Liu, WG
    Tianjin Univ, Sch Mat Sci & Engn, Tianjin 300072, Peoples R China.
    Belmonte, C
    Univ Miguel Hernandez, CSIC, Inst Neurociencias Alicante, Alacant 03550, Spain.
    Griffith, May
    Univ Ottawa, Ottawa Hosp, Inst Eye, Ottawa, ON K1H 8L6 Canada.
    Gallar, J
    Univ Miguel Hernandez, CSIC, Inst Neurociencias Alicante, Alacant 03550, Spain.
    Regeneration of functional nerves within full thickness collagen-phosphorylcholine corneal substitute implants in guinea pigs2010Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 31, nr 10, s. 2770-2778Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Our objective was to evaluate promotion of tissue and nerve regeneration by extracellular matrix (ECM) Mimics, using corneal implantation as a model system. Porcine type I collagen and 2-methacryloyloxyethyl phosphorylcholine (MPC) were crosslinked using 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) and moulded into appropriate corneal dimensions to serve as substitutes for natural corneal ECK These were implanted as full thickness grafts by penetrating keratoplasty into the corneas Of guinea pigs after removal of the host tissue, and tracked over eight months, by clinical examination, slit-lamp biomicroscopy, and esthesiometry. Histopathology and ex vivo nerve terminal impulse recordings were performed at three months and at eight months. The implants promoted regeneration of corneal cells, nerves and the tear film, while retaining optical clarity. After three months, electrophysiological recordings showed evidence of mechano-nociceptors, and polymodal units inside the implants, while cold-sensitive units were present only on the peripheral host cornea. Following eight months, the incidence of nerve activity and the frequency of spontaneous firing were higher than in control eyes as reported for regenerating fibers. Active cold nerve terminals also innervated the implant area. We show that ECM mimetic materials can promote regeneration of corneal cells and functional nerves. The simplicity in fabrication and demonstrated functionality shows potential for ECM substitutes in future clinical applications. (C) 2009 Elsevier Ltd. All rights reserved.

  • 20.
    Merrett, Kimberley
    et al.
    Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
    Liu, Wenguang
    Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
    Mitra, Debbie
    Department of Chemistry, Centre for Catalysis Research and Innovation, University of Ottawa, Ottawa, ON, Canada.
    Camm, Kenneth D.
    Department of Chemistry, Centre for Catalysis Research and Innovation, University of Ottawa, Ottawa, ON, Canada.
    McLaughlin, Christopher R.
    Department of Cellular and Molecular Medicine, University of Ottawa, and University of Ottawa Eye Institute, Ottawa, ON, Canada.
    Liu, Yuwen
    University of Ottawa Eye Institute, Ottawa, ON, Canada.
    Watsky, Mitchell A.
    Department of Physiology, University of Tennessee Health Sciences Centre, Memphis, TN, USA.
    Li, Fengfu
    University of Ottawa Eye Institute, Ottawa, ON, Canada.
    Griffith, May
    Department of Cellular and Molecular Medicine, University of Ottawa, and University of Ottawa Eye Institute, Ottawa, ON, Canada.
    Fogg, Deryn E.
    Department of Chemistry, Centre for Catalysis Research and Innovation, University of Ottawa, Ottawa, ON, Canada.
    Synthetic neoglycopolymer-recombinant human collagen hybrids as biomimetic crosslinking agents in corneal tissue engineering2009Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 30, nr 29, s. 5403-5408Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Saturated neoglycopolymers, prepared via tandem ROMP-hydrogenation (ROMP = ring-opening metathesis polymerization) of carbohydrate-functionalized norbornenes, are investigated as novel collagen crosslinking agents in corneal tissue engineering. The neoglycopolymers were incorporated into recombinant human collagen type III (RHC III) as collagen crosslinking agents and glycosaminoglycan (GAG) mimics. The purely synthetic nature of these composites is designed to reduce susceptibility to immunological and allergic reactions, and to circumvent the transmission of animal infectious diseases. The collagen-neoglycopolymer biomaterials exhibit higher stability to collagenase-induced biodegradation than the control materials, composites of RHC III crosslinked using EDC/NHS (EDC = 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide; NHS = N-hydroxysuccinimide). Even at this proof of concept stage, the thermal stability, enzymatic resistance, and permeability of the neoglycopolymer hydrogels are comparable or superior to those of these fully optimized control materials, which have successfully been tested clinically. Tensile strength is adequate for transplantation, but lower than that of the optimized control materials.

  • 21. Nimeri, G
    et al.
    Öhman, Lena
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Infektionsmedicin. Östergötlands Läns Landsting, Medicincentrum, Infektionskliniken i Östergötland.
    Elwing, H
    Wetterö, Jonas
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi.
    Bengtsson, Torbjörn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi.
    The influence of plasma proteins and platelets on oxygen radical production and F-actin distribution in neutrophils adhering to polymer surfaces2002Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 23, nr 8, s. 1785-1795Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is well known that blood cell interactions with artificial surfaces might have deleterious effects on host tissue, however, the mechanisms involved are far from understood. In this study, neutrophil-platelet interaction on uncoated or protein-coated polymer surfaces was investigated. Cell spreading, reorganization of actin filaments and release of oxygen metabolites (measured as luminol-amplified chemiluminescence) were used as criteria for cell activation on positively charged, hydrophilic 1,2-diaminocyclohexane, and negatively charged, hydrophobic hexamethylene-disiloxane. The model surfaces were made by radio frequency plasma discharge polymerization. Neutrophil contact with the uncoated polymers induced a prolonged generation of oxygen radicals. Precoating of the polymer surfaces with human serum albumin (HSA) or fibrinogen, markedly reduced neutrophil activation, whereas coating with human immunoglobulin G (IgG), a well-known opsonin, resulted in significantly higher levels of cell activation. Consequently, protein coating overruled the activating effects of the polymer surfaces. The presence of unstimulated or thrombin-stimulated platelets markedly increased the reactivity of neutrophils against fibrinogen- and IgG-coated surfaces. However, neutrophils remained relatively unreactive in the presence of platelets on HSA-treated surfaces. Comparison of the different types of surfaces used, reveals a correlation between the degree of cell spreading, reorganization of the actin cytoskeleton and the amount of oxygen radicals produced. Our results suggest that the acute inflammatory reaction on a biomaterial surface is highly dependent on the nature and composition of the first adsorbed protein layer and the extent of platelet activation.

  • 22.
    Nordgren, Anders
    Linköpings universitet, Institutionen för religion och kultur.
    Moral imagination in tissue engineering research on animal models2004Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 25, s. 1723-1734Artikel i tidskrift (Refereegranskat)
  • 23.
    Rafat, Mehrdad
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Ottawa Hospital Research Institute, Ottawa Hospital, General Division, Ottawa, Canada.
    Cléroux, Carolyne A.
    Ottawa Hospital Research Institute, Ottawa Hospital, General Division, Ottawa, Canada.
    Fong, Wai Gin
    Ottawa Hospital Research Institute, Ottawa Hospital, General Division, Ottawa, Canada.
    Baker, Adam N.
    Ottawa Hospital Research Institute, Ottawa Hospital, General Division, Ottawa, Canada.
    Leonard, Brian C.
    Ottawa Hospital Research Institute, Ottawa Hospital, General Division, Ottawa, Canada.
    O'Connor, Michael D.
    Ottawa Hospital Research Institute, Ottawa Hospital, General Division, Ottawa, Canada.
    Tsilfidis, Catherine
    Ottawa Hospital Research Institute, Ottawa Hospital, General Division, Ottawa, Canada.
    PEG-PLAmicroparticles for encapsulation and delivery of Tat-EGFP to retinal cells2010Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 31, nr 12, s. 3414-3421Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The efficient and controlled delivery of genes and proteins to retinal cells remains a challenge. In this study, we evaluated polyethylene glycol-polylactic acid (PEG–PLA) microparticles for encapsulation and delivery of a Transactivator of transcription-enhanced green fluorescent protein fusion (Tat-EGFP) to retinal cells. Our main objective was to develop a microparticle system that delivers Tat-EGFP with an initial rapid release (within 24 h) followed by a sustained release. We prepared four different formulations of Tat-EGFP encapsulated PEG–PLA particles to investigate the effects of protein and polymer concentrations on particle morphology and protein release, using scanning electron microscopy (SEM) and fluorometry techniques. The optimum formulation was selected based on higher protein release, and smaller particle size. The optimum formulation was then tested in vitro for cell biocompatibility and protein internalization, and in vivo for cellular toxicity following sub-retinal injections into rat eyes. The results suggest that PEG–PLA microparticles can deliver proteins in cell culture allowing protein internalization in as little as 1 h. In vivo, protein was shown to localize within the photoreceptor layer of the retina, and persist for at least 9 weeks with no observed toxicity.

  • 24.
    Rafat, Mehrdad
    et al.
    Department of Chemical Engineering University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
    Li, Fengfu
    University of Ottawa Eye Institute, Ottawa, Ontario K1H 8L6, Canada.
    Fagerholm, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmiatrik. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US.
    Lagali, Neil S.
    University of Ottawa Eye Institute, Ottawa, Ontario K1H 8L6, Canada.
    Watsky, Mitchell A.
    University of Tennessee Health Center, Memphis, TN, USA.
    Munger, Rejean
    University of Ottawa Eye Institute, Ottawa, Ontario K1H 8L6, Canada.
    Matsuura, Takeshi
    Department of Chemical Engineering University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
    Griffith, May
    University of Ottawa Eye Institute, Ottawa, Ontario K1H 8L6, Canada.
    PEG-stabilized carbodiimide crosslinked collagen-chitosan hydrogels for corneal tissue engineering2008Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 29, nr 29, s. 3960-3972Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Implantable biomaterials that mimic the extracellular matrix (ECM) in key physical and physiological functions require components and microarchitectures that are carefully designed to maintain the correct balance between biofunctional and physical properties. Our goal was to develop hybrid polymer networks (HPN) that combine the bioactive features of natural materials and physical characteristics of synthetic ones to achieve synergy between the desirable mechanical properties of some components with the biological compatibility and physiological relevance of others. In this study, we developed collagen-chitosan composite hydrogels as corneal implants stabilized by either a simple carbodiimide cross-linker or a hybrid cross-linking system comprised of a long-range bi-functional cross-linker (e.g. poly(ethylene glycol) dibutyraldehyde (PEG-DBA)), and short-range amide-type cross-linkers (e.g. 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), and N-hydroxysuccinimide (NHS)). Optimum hybrid hydrogel demonstrated significantly enhanced mechanical strength and elasticity by 100 and 20%, respectively, compared to its non-hybrid counterpart. It demonstrated excellent optical properties, optimum mechanical properties and suturability, and good permeability to glucose and albumin. It had excellent biocompatibility and when implanted into pig corneas for 12 months, allowed seamless host-graft integration with successful regeneration of host corneal epithelium, stroma, and nerves. © 2008 Elsevier Ltd. All rights reserved.

  • 25.
    Rafat, Mehrdad
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska fakulteten.
    Xeroudaki, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM. Linköpings universitet, Medicinska fakulteten.
    Koulikovska, Marina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM. Linköpings universitet, Medicinska fakulteten.
    Sherrell, Peter
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska fakulteten.
    Groth, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM. Linköpings universitet, Medicinska fakulteten.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM. Linköpings universitet, Medicinska fakulteten.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM.
    Composite core-and-skirt collagen hydrogels with differential degradation for corneal therapeutic applications2016Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 83, s. 142-155Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Scarcity of donor tissue to treat corneal blindness and the need to deliver stem cells or pharmacologic agents to ensure corneal graft survival are major challenges. Here, new composite collagen-based hydrogels are developed as implants to restore corneal transparency while serving as a possible reservoir for cells and drugs. The composite hydrogels have a centrally transparent core and embedded peripheral skirt of adjustable transparency and degradability, with the skirt exhibiting faster degradation in vitro. Both core and skirt supported human epithelial cell populations in vitro and the skirt merged homogeneously with the core material to smoothly distribute a mechanical load in vitro. After in vivo transplantation in rabbit corneas over three months, composites maintained overall corneal shape and integrity, while skirt degradation could be tracked in vivo and non-invasively due to partial opacity. Skirt degradation was associated with partial collagen breakdown, thinning, and migration of host stromal cells and macrophages, while the central core maintained integrity and transparency as host cells migrated and nerves regenerated.

    IMPACT:

    This study indicates the feasibility of a collagen-based composite hydrogel to maintain corneal stability and transparency while providing a degradable peripheral reservoir for cell or substance release.

  • 26.
    Suska, F
    et al.
    Gothenburg Univ, Sahlgrenska Acad, Inst Surg Sci, Dept Biomat, SE-40530 Gothenburg, Sweden Linkoping Univ, Appl Phys Lab, SE-58183 Linkoping, Sweden.
    Esposito, M
    Gothenburg Univ, Sahlgrenska Acad, Inst Surg Sci, Dept Biomat, SE-40530 Gothenburg, Sweden Linkoping Univ, Appl Phys Lab, SE-58183 Linkoping, Sweden.
    Gretzer, C
    Gothenburg Univ, Sahlgrenska Acad, Inst Surg Sci, Dept Biomat, SE-40530 Gothenburg, Sweden Linkoping Univ, Appl Phys Lab, SE-58183 Linkoping, Sweden.
    Kalltorp, M
    Gothenburg Univ, Sahlgrenska Acad, Inst Surg Sci, Dept Biomat, SE-40530 Gothenburg, Sweden Linkoping Univ, Appl Phys Lab, SE-58183 Linkoping, Sweden.
    Tengvall, Pentti
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik.
    Thomsen, P
    Gothenburg Univ, Sahlgrenska Acad, Inst Surg Sci, Dept Biomat, SE-40530 Gothenburg, Sweden Linkoping Univ, Appl Phys Lab, SE-58183 Linkoping, Sweden.
    IL-1 alpha, IL-1 beta and TNF-alpha secretion during in vivo/ex vivo cellular interactions with titanium and copper (vol 24, pg 461, 2003)2003Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 24, nr 9, s. 1683-1683Övrigt (Övrigt vetenskapligt)
  • 27.
    Suska, F.
    et al.
    Department of Biomaterials, Institute of Surgical Sciences, Sahlgrenska Academy at Göteborg University, SE-405 30 Göteborg, Sweden.
    Esposito, M.
    Department of Biomaterials, Institute of Surgical Sciences, Sahlgrenska Academy at Göteborg University, SE-405 30 Göteborg, Sweden.
    Gretzer, C.
    Department of Biomaterials, Institute of Surgical Sciences, Sahlgrenska Academy at Göteborg University, SE-405 30 Göteborg, Sweden.
    Kalltorp, M.
    Källtorp, M., Department of Biomaterials, Institute of Surgical Sciences, Sahlgrenska Academy at Göteborg University, SE-405 30 Göteborg, Sweden.
    Tengvall, Pentti
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik.
    Thomsen, P.
    Department of Biomaterials, Institute of Surgical Sciences, Sahlgrenska Academy at Göteborg University, SE-405 30 Göteborg, Sweden.
    IL-1a, IL-1ß and TNF-a secretion during in vivo/ex vivo cellular interactions with titanium and copper2003Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 24, nr 3, s. 461-468Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Titanium (Ti) and copper (Cu) were used to evaluate cytokine secretion around materials with different chemical properties. Ti disks were coated with Cu or left uncoated. The disks were inserted subcutaneously in rats for 1, 3, 12, 18, 24 and 48h. Interleukin-1a (IL-1a), IL-1ß and tumor necrosis factor-a (TNF-a) concentrations were measured in vivo around the materials, in sham operated sites, and after ex vivo incubation of surface adherent cells. Ti and Cu revealed distinct cytokine expression patterns. Cu recruited cells showed higher and prolonged release of IL-1a than Ti at longer times (>24h), whereas Ti exhibited a transient IL-1a response at earlier periods (<24h). An early enhanced secretion of TNF-a characterized Ti. Low amounts of IL-1ß were found around both materials. Sham site recruited cells produced lower levels of cytokines. The results after ex vivo incubations were similar to those in vivo. This study shows that material chemical properties influence early cytokine production. The Ti-associated transient rise of IL-1a and TNF-a may be of importance for the early tissue response around biocompatible materials, while a delayed high IL-1a expression could be a marker of inflammation induced by toxic materials. © 2002 Elsevier Science Ltd. All rights reserved.

  • 28.
    Suska, Felicia
    et al.
    Dept. of Biomaterials, Inst. of Surgical Sciences Sahlgrenska Academy at Göteborg University.
    Gretzer, Christina
    Dept. of Biomaterials, Inst. of Surgical Sciences Sahlgrenska Academy at Göteborg University.
    Esposito, Marco
    Dept. of Biomaterials, Inst. of Surgical Sciences Sahlgrenska Academy at Göteborg University.
    Emanuelsson, Lena
    Dept. of Biomaterials, Inst. of Surgical Sciences Sahlgrenska Academy att Göteborg University.
    Wennerberg, Ann
    Dept. of Biomaterials, Inst. of Surgical Sciences Sahlgrenska Academy at Göteborg University.
    Tengvall, Pentti
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik.
    Thomsen, Peter
    Dept. of Biomaterials, Inst. of Surgical Sciences Sahlgrenska Academy at Göteborg University.
    In vivo cytokine secretion and NF-κB activation around titanium and copper implants2005Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 26, nr 5, s. 519-527Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The early biological response at titanium (Ti), copper (Cu)-coated Ti and sham sites was evaluated in an in vivo rat model. Material surface chemical and topographical properties were characterized using Auger electron spectroscopy, energy dispersive X-ray spectroscopy and interferometry, respectively. The number of leukocytes, cell types and cell viability (release of lactate dehydrogenase) were determined in the implant-interface exudate. The contents of activated nuclear transcription factor NF-κB, interleukin-6 (IL-6) and interleukin-10 (IL-10) were determined by enzyme linked immunosorbent assay. An increase in the number of leukocytes, in particular, polymorphonuclear leukocytes, was observed between 12 and 48h around Cu. A marked decrease of exudate cell viability was found around Cu after 48h. The total amounts of activated NF-κB after 12h was highest in Ti exudates whereas after 48h the highest amount of NF-κB was detected around Cu. The levels of cytokine IL-6 were consistently high around Cu at both time periods. No differences in IL-10 contents were detected, irrespective of material/sham and time. The results show that materials with different toxicity grades (titanium with low and copper with high toxicity) exhibit early differences in the activation of NF-κB, extracellular expression and secretion of mediators, causing major differences in inflammatory cell accumulation and death in vivo. © 2004 Elsevier Ltd. All rights reserved.

  • 29.
    Suska, Felicia
    et al.
    Dept. of Biomaterials, Inst. of Surgical Sciences Sahlgrenska Academy at Göteborg University.
    Gretzer, Christina
    Dept. of Biomaterials, Inst. of Surgical Sciences Sahlgrenska Academy at Göteborg University.
    Esposito, Marco
    Dept. of Biomaterials, Inst. of Surgical Sciences Sahlgrenska Academy at Göteborg University.
    Tengvall, Pentti
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik.
    Thomsen, Peter
    Dept. of Biomaterials, Inst. of Surgical Sciences Sahlgrenska Academy at Göteborg University.
    Monocyte viability on titanium and copper coated titanium2005Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 26, nr 30, s. 5942-5950Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The role of apoptosis/cell death in the inflammatory response at the implanted materials is unexplored. Two surfaces with different cytotoxic potential and in vivo outcomes, titanium (Ti) and copper (Cu) were incubated in vitro with human monocytes and studied using a method to discriminate apoptotic and necrotic cells (Annexin V/PI staining). Further, staurosporine, a potent inducer of apoptosis, was added to the surface adherent monocytes. Lactate dehydrogenase (a marker of cell membrane injury) and TNF-α and IL-10, cytokines, previously suggested to play a major role in the monocyte apoptosis, were assayed in the culture medium. The results demonstrated that Ti surfaces displayed enhanced monocyte survival and production of IL-10 and TNF-α. Cu adherent cells exhibited apoptotic signs as early as 1 h after incubation. In contrast to Ti, after 48 h the predominance of apoptotic cells switched to apoptotic/necrotic cells on Cu surfaces. Staurosporine treatment of Ti adherent cells mediated similar type of cell death. LDH and cytokine contents were low around Cu surfaces, partly explained by interference between Cu ions and LDH and cytokines. This study suggests that material properties rapidly influence the onset of human monocyte apoptosis and progression to late apoptosis/necrosis. Early detection of apoptosis and cell death may be important for the understanding of the biological response to implanted materials. © 2005 Elsevier Ltd. All rights reserved.

  • 30.
    Svennersten, Karl
    et al.
    Karolinska Institutet.
    Bolin, Maria H.
    Linköpings universitet, Institutionen för teknik och naturvetenskap. Linköpings universitet, Tekniska högskolan.
    Jager, Edwin W.H.
    Linköpings universitet, Institutionen för teknik och naturvetenskap. Linköpings universitet, Tekniska högskolan.
    Berggren, Magnus
    Linköpings universitet, Institutionen för teknik och naturvetenskap. Linköpings universitet, Tekniska högskolan.
    Richter-Dahlfors, Agneta
    Karolinska Institutet.
    Electrochemical modulation of epithelia formation using conducting polymers2009Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 30, nr 31, s. 6257-6264Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Conducting polymers are soft, flexible materials, exhibiting material properties that can be reversibly changed by electrochemically altering the redox state. Surface chemistry is an important determinant for the molecular events of cell adhesion. Therefore, we analyzed whether the redox state of the conducting polymer PEDOT:Tosylate can be used to control epithelial cell adhesion and proliferation. A functionalized cell culture dish comprising two adjacent electrode surfaces was developed. Upon electronic addressing, reduced and oxidized surfaces are created within the same device. Simultaneous analysis of how a homogenous epithelial MDCK cell population responded to the electrodes revealed distinct surface-specific differences. Presentation of functional fibronectin on the reduced electrode promoted focal adhesion formation, involving αvβ3 integrin, cell proliferation, and ensuing formation of polarized monolayers. In contrast, the oxidized surface harbored only few cells with deranged morphology showing no indication of proliferation. This stems from the altered fibronectin conformation, induced by the different surface chemistry of the PEDOT:Tosylate electrode in the oxidized state. Our results demonstrate a novel use of PEDOT:Tosylate as a cell-hosting material in multiple-electrode systems, where cell adhesion and proliferation can be controlled by electrochemical modulation of surface properties.

  • 31.
    Tosatti, S.
    et al.
    Lab. for Surf. Sci. and Technology, Department of Materials, Swiss Fed. Inst. Technol. (ETH) Z., CH-8092 Zurich, Switzerland.
    De, Paul S.M.
    De Paul, S.M., Lab. for Surf. Sci. and Technology, Department of Materials, Swiss Fed. Inst. Technol. (ETH) Z., CH-8092 Zurich, Switzerland, Solvias AG, Klybeckstrasse 191, CH-4002 Basel, Switzerland.
    Askendal, Agneta
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi.
    VandeVondele, S.
    Institute for Biomedical Engineering, Department of Materials, ETH and University of Zurich, CH-8092 Zurich, Switzerland.
    Hubbell, J.A.
    Institute for Biomedical Engineering, Department of Materials, ETH and University of Zurich, CH-8092 Zurich, Switzerland.
    Tengvall, Pentti
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik.
    Textor, M.
    Lab. for Surf. Sci. and Technology, Department of Materials, Swiss Fed. Inst. Technol. (ETH) Z., CH-8092 Zurich, Switzerland.
    Peptide functionalized poly(L-lysine)-g-poly(ethylene glycol) on titanium: Resistance to protein adsorption in full heparinized human blood plasma2003Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 24, nr 27, s. 4949-4958Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The graft copolymer poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) and its RGD- and RDG-functionalized derivatives (PLL-g-PEG/PEG-peptide) were assembled from aqueous solutions on titanium (oxide) surfaces. The polymers were characterized by NMR in order to determine quantitatively the grafting ratio, g (Lys monomer units/PEG side chains), and the fraction of the PEG side chains carrying the terminal peptide group. The titanium surfaces modified with the polymeric monomolecular adlayers were exposed to full heparinized blood plasma. The adsorbed masses were measured by in situ ellipsometry. The different PLL-g-PEG-coated surfaces showed, within the detection limit of the ellipsometric technique, no statistically significant protein adsorption during exposure to plasma for 30min at 22°C or 37°C, whereas clean, uncoated titanium surfaces adsorbed approximately 350ng/cm2 of plasma proteins. The high degree of resistance of the PEGylated surface to non-specific adsorption makes peptide-modified PLL-g-PEG a useful candidate for the surface modification of biomedical devices such as implants that are capable of eliciting specific interactions with integrin-type cell receptors even in the presence of full blood plasma. The results refer to short-term blood plasma exposure that cannot be extrapolated a priori to long-term clinical performance. © 2003 Elsevier Ltd. All rights reserved.

  • 32.
    Wetterö, Jonas
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Tekniska högskolan.
    Askendal, Agneta
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik. Linköpings universitet, Tekniska högskolan.
    Bengtsson, Torbjörn
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Tengvall, Pentti
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik. Linköpings universitet, Tekniska högskolan.
    On the binding of complement to solid artificial surfaces in vitro2002Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 23, nr 4, s. 981-991Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Since the realization of a complement activation capacity by artificial surfaces upon contact with blood, a common belief has evolved that charged nucleophilic surface groups such as amine (–NH2) and hydroxyl (–OH) react with and eventually bind to the internal thioester in complement factor 3 (C3). A covalent amide or ester linkage is thereby supposed to form between C3b and the surface itself. In this report, we present complement surface binding data by null-ellipsometry for two nucleophilic surfaces (–NH2 and –OH), for surfaces with immunoglobulin G (IgG) covalently bound, and for IgG spontaneously pre-adsorbed to hydrophobic silicon. The results reveal that the plasma proteins that were deposited during complement activation became eluted by sodium dodecyl sulfate. Hence the direct covalent binding between C3 and solid nucleophilic surfaces seems to be only of moderate importance, at least during shorter serum incubations. This strongly suggests that the prevalent covalent linkage model between solid artificial surfaces and C3b is not accurate. Instead we suggest a more pronounced role for C3 associations to other adsorbed proteins and/or electrostatic and hydrophobic protein–surface interactions.

  • 33.
    Wetterö, Jonas
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Tekniska högskolan.
    Tengvall, Pentti
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik. Linköpings universitet, Tekniska högskolan.
    Bengtson, Torbjörn
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Platelets stimulated by IgG-coated surfaces bind and activate neutrophils through a selectin-dependent pathway2003Ingår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 24, nr 9, s. 1559-1573Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Blood platelets bind rapidly to foreign surfaces and interact with adsorbed proteins and neutrophil granulocytes. We demonstrate by use of luminol-amplified chemiluminescence under stirred and non-stirred conditions that platelets at IgG-coated surfaces amplify the neutrophil extracellular release of reactive oxygen species (ROS). The neutrophil response involved tyrosine phosphorylation, but was only in part induced by neutrophil Fcγ-receptor stimulation. The platelet mediated effects were contact-dependent since the respiratory burst was inhibited when the IgG-stimulated platelets were removed by filtration, but not when they were fixed in paraformaldehyde. Bodipyphallacidin-staining of filamentous actin (F-actin) revealed that an actin-dependent platelet adhesion supported the subsequent adhesion and spreading of neutrophils. The neutrophil ROS-response was lowered when the interaction between platelet P-selectin (CD62P) and neutrophil P-selectin glycoprotein ligand-l (PSGL-1 or CD162) was inhibited. The blocking of L-selectin (CD62L) or blocking of the interaction between platelet glycoprotein (Gp) IIb/IIIa and neutrophil complement receptor 3 (CR3) showed no effect. We conclude that platelet activation on immobilized IgG trigger a contact-dependent “frustrated” phagocytosis by neutrophils, associated with a release of toxic ROS.

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