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  • 101.
    Rafat, Mehrdad
    et al.
    Device Surveillance Division, Medical Devices Bureau, HPFB, Health Canada, Ottawa, Canada.
    Karov, J.
    Device Surveillance Division, Medical Devices Bureau, HPFB, Health Canada, Ottawa, Canada.
    Griffith, May
    Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
    Courtman, D.
    The Ottawa Hospital Research Institute, Ottawa, Canada.
    Arzhangi, Z.
    Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
    Daka, J.N.
    Research and Radiation Directorate, Healthy Environment and Consumer Safety, Health Canada, Ottawa, Canada.
    Development and Safety Evaluation of Nanomaterials for Encapsulation andDelivery of Stem Cells to Dysfunctional Heart Tissue2009Ingår i: Book of Abstracts 2009, Health CanadaScience Forum, Health Canada Science Plan -Implementing Health Canada’s Science and Technology Strategy, 2009Konferensbidrag (Refereegranskat)
    Abstract [en]

    SUMMARY: Tissue-specific delivery of stem cells holds the potential to regenerate damaged heart tissue and to restore its functions after Myocardial Infarction. In this study we describe a novel cell encapsulation technique for target delivery of stem cells to damaged heart tissue. This research is conducted in collaboration with OHRI and UOttawa.

    BACKGROUND/ISSUE(S)/OBJECTIVES: Heart failure is the number one cause of death in developed countries. Stem cell transplantation has drawn a lot of attention as a promising therapy for heart disease. However, extensive cell attrition, and loss at the site of transplantation present a limit to therapeutic efficacy. We have hypothesized that by encapsulating the cells in naturally-derived materials, e.g., collagen and alginate, cells viability, and target delivery can be enhanced. Our main objective is to develop encapsulation techniques for effective delivery of stem cells. The other objective is to develop characterization techniques for safety evaluation of such systems at nano and micro scales.

    DESIGN/METHOD/DESCRIPTION: Novel collagen-alginate microspheres loaded with GFP-BOEC cells (green florescence expressing -blood outgrowth endothelial cells) were developed. The method involves the gelation of a hybrid collagenalginate- cell solution using a drop-wise technique in a calcium chloride bath. Microspheres were washed and transferred to a Petri dish containing  culture medium and incubated at 37°C. Microspheres formation, and morphology (shape and size) and viability of the cells were monitored using a Nikon inverted light microscope.

    OUTPUTS/RESULTS: Light microscopy images suggest successful formation of hybrid collagen-alginate microspheres in a size range of about 1000-2000 μm. The images also show that cells fluoresce an apple green when excited with near UV light implying that most of the cells are viable.

    IMPACTS/OUTCOMES/CONCLUSIONS/IMPLICATIONS/NEXT STEPS: Preliminary results from these experiments reveal that GFP-BOEC cells can be encapsulated in collagen-alginate microspheres. The results suggest that cells are viable over a period of three days. Also, light microscopy techniques were successfully utilized for physical (i.e., shape and size) and biological (i.e., viability) characterizations of microspheres. The next steps will include the use of Mesenchymal Stem Cells instead of GFP-BOEC, fine-tuning of material formulations, and further characterizations, i.e., scanning electron microscopy (SEM). We anticipate that this work will help us to better understand new emerging technologies such as nanotechnology, stem cells therapeutics, and tissue engineering that will ultimately benefit the regulatory process of medical   products that are based on such technologies.

  • 102.
    Rafat, Mehrdad
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Koh, Li Buay
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Liedberg, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Highly elastic epoxycross‐linked collagen hydrogels for corneal tissueengineering2012Ingår i: Acta Ophthalmologica; Special Issue: Abstracts from the 2012 European Association for Vision and Eye Research Conference, Volume 90, Issue Supplement s249, page 0, September 2012, John Wiley & Sons, 2012Konferensbidrag (Refereegranskat)
    Abstract [en]

    Purpose Our objective is to develop novel materials that support the regeneration of diseased or damaged corneas. Despite the promising clinical results that we previously reported on biosynthetic corneas, more robust and elastic materials are required to withstand the adverse host conditions faced for high risk transplantation in severely damaged or diseased corneas. This presentation will provide details on an epoxy cross-linked collagen-based scaffold with enhanced mechanical properties.

    Methods We have developed a range of collagen-based materials as mimics of the cell-free corneal stromal extracellular matrix. In this study, cross-linked polymer networks of collagen hydrogels were prepared using a hybrid of 1,4-butanediol diglycidyl ether (BDDGE) and carbodiimides (e.g. EDC-NHS) as cross-linkers. Briefly, 10w/w% porcine collagen type I was mixed in a T-piece system at various compositions and pH, e.g. pH 5, pH 11, and incorporated with laminin adhesive peptides (YIGSR, and IKVAV). Promising material formulations were tested for their physiochemical properties (e.g. mechanical, optical, water uptake, FTIR, and thermal degradation) and physiological properties (e.g. interactions with corneal cells, and biodegradation).

    Results The hybrid BDDGE hydrogels demonstrated improved mechanical properties and degree of cross-linking while maintaining their optical clarity and biocompatibility compared to controls (e.g. EDC/NHS-crosslinked hydrogels). Incorporation of laminin-derived cell-adhesive peptide (IKVAV) demonstrated significant increase in corneal cells (HCECs) proliferation compared to controls.

    Conclusion The hybrid BDDGE-crosslinked collagen-based hydrogels have the potential for use as tissue-engineered corneal substitutes.

  • 103.
    Rafat, Mehrdad
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM.
    Koulikovska, Marina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM.
    In vivo integrity of intra‐corneal bioengineered discs in rabbit models2013Ingår i: Acta Ophthalmologica; Special Issue: Abstracts from the 2013 European Association for Vision and Eye Research Conference, August 2013 Volume 91, Issue Supplement s252, John Wiley & Sons, 2013Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Background: We have previously reported the successful integration and safety of bioengineered materials as corneal substitutes in human models. Despite the promising results as corneal implants, more elastic and robust materials are required for use as thin intra-corneal lenses to withstand surgical manipulation for corrective surgery and improved vision. Most of the existing corneal inlays are made of synthetic materials. Here we describe the potential of bioengineerd materials for vision correction. Objectives: to develop bioengineered materials as inlays within the corneal tissue as well as evaluating the in vivo integrity and integration of the materials in rabbit models. Methods: Bioengineered inlays were prepared from collagen and tested for their physical and biological propertis. A femtosecond laser was used to cut 100 mircon thick discs of mid-stromal tissue from corneas of 20 rabbits and replaced with bioengineered inlays. Results: The new materials demonstrated improved mechanical properties while maintaining their clarity and biocompatibility. The bioengineered inlays retained their shapes, thickness, and clarity 8 weeks post-surgery in rabbits.

  • 104.
    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.

  • 105.
    Rafat, Mehrdad
    et al.
    Department of Chemical Engineering, University of Ottawa, Ottawa, Canada.
    Matsuura, T.
    Department of Chemical Engineering, University of Ottawa, Ottawa, Canada.
    Griffith, May
    Department of Chemical Engineering, University of Ottawa, Ottawa, Canada.
    Surface Modification and Characterization of Artificial Cornea for Reduced Endothelialization2006Konferensbidrag (Övrigt vetenskapligt)
  • 106.
    Rafat, Mehrdad
    et al.
    Department of Chemical Engineering, University of Ottawa and University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Matsuura, Takeshi
    Department of Chemical Engineering, University of Ottawa, Ottawa, Ontario, Canada.
    Li, Fengfu
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Griffith, May
    University of Ottawa Eye Institute and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
    Surface modification of collagen-based artificial cornea for reduced endothelialization2009Ingår i: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, Vol. 88A, nr 3, s. 755-768Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Our objective was to develop collagen-based hydrogels as tissue substitutes for corneal transplantation The design of the full-thickness corneal grafts includes prevention of cell migration onto the posterior surface of the implants, using a plasma-assisted surface modification technique. Briefly, the hydrogel materials were Subjected to ammonia plasma functionalization followed by grafting of alginate macromolecules to the target surface. The treated materials Surfaces showed observable decreases in endothelial cell attachment. The decrease in cell attachment and adhesion was dependant upon the concentration of alginate and plasma radio frequency (RF) power. High concentrations of alginate 5%, (w/v) and high I F power of 100 W produced surfaces with minimal cell attachment. The plasma-alginate treatment did not adversely affect the optical or swelling properties of the constructs. Contact angle measurement analysis revealed that the posterior surface hydrophilicity significantly increased after the treatment. The grafting of alginate to the implants surfaces was confirmed by fourier transform infrared spectroscopy. Both of the untreated and alginate grafted corneal materials were found to be superior to human cornea in optical and swelling properties.

  • 107.
    Rafat, Mehrdad
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Mondal, Debasish
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Islam, M.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Liedberg, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Nanoparticles incorporated collagen hydrogels for sustained release of EGF2013Ingår i: Acta Ophthalmologica; Special Issue: Abstracts from the 2013 European Association for Vision and Eye Research Conference, Volume 91, Issue Supplement s252, page 0, August 2013, John Wiley & Sons, 2013Konferensbidrag (Refereegranskat)
    Abstract [en]

    Therapeutic biomolecules such as growth factors are essential for enhancing the regeneration of damaged tissues by inducing cell signaling activities such as cell migration, proliferation, and differentiation. Nevertheless, they have short half-lives in physiological conditions due to fast deactivation and degradation by enzymes and other physical and chemical reactions. Therefore, there is a great need for the suitable target delivery of nanoparticles to improve the release kinetics of growth factors as well as their therapeutic effectiveness. The main objective of this study was to develope and characterize a sustained delivery system consisting of an EGF-encapslated chitosan nanoparticles and collagen hydrogel carrier system to achieve a sustained release of EGF. In this study, we made EGF-loaded chitosan nanoparticles, which could be incorporated into an engineered collagen hydrogel scaffold. The particles were spherical in the size range of 60–100 nm. The release kinetics of EGF showed the release of growth factors in a sustained manner. Live-dead staining of human corneal epithelial (HCEC) cells was done to evaluate the cytotoxicity of the nanoparticles.

  • 108.
    Rajendran, Vijayalakshmi
    et al.
    University of Aberdeen, Scotland.
    Netukova, Magdalena
    Charles University of Prague, Czech Republic.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. University of Montreal, Canada.
    Forrester, John V.
    University of Aberdeen, Scotland; University of Western Australia, Australia; Lions Eye Institute, Australia.
    Kuffova, Lucia
    University of Aberdeen, Scotland.
    Mesenchymal stem cell therapy for retro-corneal membrane - A clinical challenge in full-thickness transplantation of biosynthetic corneal equivalents2017Ingår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 64, s. 346-356Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 109.
    Ravichandran, Ranjithkumar
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska högskolan.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Phopase, Jaywant
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska högskolan.
    Applications of self-assembling peptide scaffolds in regenerative medicine: the way to the clinic2014Ingår i: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 2, nr 48, s. 8466-8478Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Peptides that self-assemble into well-defined nanofibrous networks provide a prominent alternative to traditional biomaterials for fabricating scaffolds for use in regenerative medicine and other biomedical applications. Such scaffolds can be generated by decorating a peptide backbone with other bioactives such as cell specific adhesion peptides, growth factors and enzyme cleavable sequences. They can be designed to mimic the three-dimensional (3D) structural features of native ECM and can therefore also provide insight into the ECM-cell interactions needed for development of scaffolds that can serve as regeneration templates for specific target tissues or organs. This review highlights the potential application of self-assembling peptides in regenerative medicine.

  • 110.
    Ravichandran, Ranjithkumar
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Islam, M. M.
    Karolinska Institute, Sweden.
    Alarcon, E. I.
    University of Ottawa, Canada; Fac Med, Canada.
    Samanta, Ayan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Wang, S.
    Uppsala University, Sweden.
    Lundström, Patrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Hilborn, J.
    Uppsala University, Sweden.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Phopase, Jaywant
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Correction: Functionalised type-1 collagen as a hydrogel building block for bio-orthogonal tissue engineering applications (vol 4, pg 318, 2016)2017Ingår i: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 5, nr 26, s. 5284-5284Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 111.
    Ravichandran, Ranjithkumar
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Islam, M. M.
    Karolinska Institute, Sweden; .
    Alarcon, E. I.
    University of Ottawa, Canada; .
    Samanta, Ayan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Wang, S.
    Uppsala University, Sweden.
    Lundström, Patrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Hilborn, J.
    Uppsala University, Sweden.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Phopase, Jaywant
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Functionalised type-I collagen as a hydrogel building block for bio-orthogonal tissue engineering applications2016Ingår i: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 4, nr 2, s. 318-326Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this study, we derivatized type I collagen without altering its triple helical conformation to allow for facile hydrogel formation via the Michael addition of thiols to methacrylates without the addition of other crosslinking agents. This method provides the flexibility needed for the fabrication of injectable hydrogels or pre-fabricated implantable scaffolds, using the same components by tuning the modulus from Pa to kPa. Enzymatic degradability of the hydrogels can also be easily fine-tuned by variation of the ratio and the type of the crosslinking component. The structural morphology reveals a lamellar structure mimicking native collagen fibrils. The versatility of this material is demonstrated by its use as a pre-fabricated substrate for culturing human corneal epithelial cells and as an injectable hydrogel for 3-D encapsulation of cardiac progenitor cells.

  • 112.
    Ron-Doitch, Sapir
    et al.
    Hebrew University of Jerusalem, Israel.
    Sawodny, Beate
    Fraunhofer IGB, Germany.
    Kuehbacher, Andreas
    Fraunhofer IGB, Germany.
    Nordling David, Mirjam M.
    Hebrew University of Jerusalem, Israel.
    Samanta, Ayan
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi.
    Phopase, Jaywant
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Burger-Kentischer, Anke
    Fraunhofer IGB, Germany.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Golomb, Gershon
    Hebrew University of Jerusalem, Israel.
    Rupp, Steffen
    Fraunhofer IGB, Germany.
    Reduced cytotoxicity and enhanced bioactivity of cationic antimicrobial peptides liposomes in cell cultures and 3D epidermis model against HSV2016Ingår i: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 229, s. 163-171Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cationic antimicrobial peptides (AMPs) are part of the innate immunity, and act against a wide variety of pathogenic microorganisms by perturbation of the microorganisms plasma membrane. Although attractive for clinical applications, these agents suffer from limited stability and activity in vivo, as well as non-specific interaction with host biological membranes, leading to cytotoxic adverse effects. We hypothesized that encapsulation of AMPs within liposomes could result in reduced cytotoxicity, and with enhanced stability as well as bioactivity against herpes simplex virus 1 (HSV-1). We formulated nano-sized liposomal formulations of LL-37 and indolicidin, and their physicochemical properties, cellular uptake, in vitro cytotoxicity and antiviral efficacy have been determined. Lower cytotoxicity of LL-37 liposomes was found in comparison to indolicidin liposomes attributed to the superior physicochemical properties, and to the different degree of interaction with the liposomal membrane. The disc-like shaped LL-37 liposomes (106.8 +/- 10.1 nm, shelf-life stability of N1 year) were taken up more rapidly and to a significantly higher extent than the free peptide by human keratinocyte cell line (HaCaT), remained intact within the cells, followed by release of the active peptide within the cytoplasm and migration of the vesicles lipids to the plasma membrane. LL-37 liposomes were found significantly less toxic than both the free agent and liposomal indolicidin. In the new 3D epidermis model (immortalized primary keratinocytes) liposomal LL-37 treatment (N20 mu M), but not free LL-37, efficiently protected the epidermis, inhibiting HSV-1 infection. This positive antiviral effect was obtained with no cytotoxicity even at very high concentrations (400 mu M). Thus, the antiviral activity of encapsulated LL-37 was significantly improved, expanding its therapeutic window. Liposomal LL-37 appears to be a promising delivery system for HSV therapy. (C) 2016 Elsevier B.V. All rights reserved.

  • 113.
    Samarawickrama, Chameen
    et al.
    Moorfields Eye Hosp NHS Fdn Trust, England; UCL Inst Ophthalmol, England; Univ Sydney, Australia.
    Samanta, Ayan
    Uppsala Univ, Sweden; LV Prasad Eye Inst, India.
    Liszka, Aneta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    Buznyk, Oleksiy
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. NAMS Ukraine, Ukraine.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. LV Prasad Eye Inst, India; Univ Montreal, Canada; Univ Montreal, Canada.
    Allan, Bruce
    Moorfields Eye Hosp NHS Fdn Trust, England; UCL Inst Ophthalmol, England.
    Collagen-Based Fillers as Alternatives to Cyanoacrylate Glue for the Sealing of Large Corneal Perforations2018Ingår i: Cornea, ISSN 0277-3740, E-ISSN 1536-4798, Vol. 37, nr 5, s. 609-616Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

  • 114.
    Shimmura, Shigeto
    et al.
    Department of Ophthalmology, Tokyo Dental College, Ichikawa General Hospital Cornea Center, Ichikawa, Chiba, Japan.
    Doillon, Charles J.
    Laval University Medical Center (CHUL), Laval University, Quebec, Canada.
    Griffith, May
    University of Ottawa Eye Institute, University of Ottawa, Ottawa, Ontario, Canada.
    Nakamura, Masatsugu
    Santen Pharmaceutical Co. Ltd., Nara R&D Center, Ikoma-shi, Nara, Japan.
    Gagnon, Edith
    Laval University Medical Center (CHUL), Laval University, Quebec, Canada.
    Usui, Akemi
    Department of Ophthalmology, Tokyo Dental College, Ichikawa General Hospital Cornea Center, Ichikawa, Chiba, Japan.
    Shinozaki, Naoshi
    Department of Ophthalmology, Tokyo Dental College, Ichikawa General Hospital Cornea Center, Ichikawa, Chiba, Japan.
    Tsubota, Kazuo
    Department of Ophthalmology, Tokyo Dental College, Ichikawa General Hospital Cornea Center, Ichikawa, Chiba, Japan.
    Collagen-poly(N-isopropylacrylamide)-based membranes for corneal stroma scaffolds2003Ingår i: Cornea, ISSN 0277-3740, E-ISSN 1536-4798, Vol. 22, nr 7, s. S81-S88Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To investigate the feasibility of using the biocompatibility of collagen-based blended biomaterials as cell-delivery systems in ocular surface reconstruction in vivo. Methods: Collagen-based composites that were blended with synthetic acrylamide-based polymers [poly(N-isopropylacrylamide), pNIPAAm] were transplanted into corneal pockets of white rabbits, with a 3-mm epithelial window. Epithelial cells were allowed to migrate onto the polymer. Transplanted eyes were examined daily for up to 30 days, after which animals; were killed for histologic examination. lm- munohistochemistry was performed for vimentin, a-smooth muscle actin (alpha-SMA), CD4, and CD8. Gold-chloride staining was performed to observe neuronal regrowth. Human amniotic membranes (AMs) and sham-operated corneas served as controls. All animals received topical antibiotics (levofloxacin) without the use of steroids or other immunosuppressive agents. Results: The pNIPAAm polymer allowed smooth epitheliatization of the cornea, which was similar to the epithelialization observed in sham controls and AM-transplanted eyes. Histology revealed that epithelium overlying the polymer was bundled into several layers, without the orientation observed with AM and sham controls. The polymer gradually thinned and was gradually replaced by host tissue. Vimentin- and alpha-SMA-positive cells were found in stromal pockets up to 1 month following polymer transplantation. These cells were responsible for slight subepithelial haze near the wound edge. CD4- and CD8-positive lymphocytes were also observed in the vicinity of the polymer. Gold-chloride staining showed nerve regrowth in the wound edge after 1 month and subepithelial branches after 3 months. Conclusion: Collagen-pNIPAAm blended polymers may he effective as biomaterials to be used in the early stages of lamellar stromal replacement.

  • 115.
    Simpson, Madeline J.
    et al.
    University of Ottawa, ON, Canada.
    Poblete, Horacio
    Center for Bioinformatics and Molecular Simulation, Universidad de Talca, Chile.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. University of Ottawa Eye Institute, ON, Canada.
    Alarcon, Emilio I.
    University of Ottawa, ON, Canada.
    Scaiano, Juan C.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. University of Ottawa, ON, Canada .
    Impact of Dye-Protein Interaction and Silver Nanoparticles on Rose Bengal Photophysical Behavior and Protein Photocrosslinking2013Ingår i: Photochemistry and Photobiology, ISSN 0031-8655, E-ISSN 1751-1097, Vol. 89, nr 6, s. 1433-1441Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The role of recombinant Type-I human collagen in the free form or forming AgNP@collagen on the photophysical and photochemical behavior of rose Bengal was analyzed. The formation of dye aggregates on the protein surface was experimentally observed and corroborated by docking calculations. The formation of such aggregates is believed to change the main oxidative mechanism from Type-II (singlet oxygen) to Type-I (free radical) photosensitization. Remarkably, the presence of AgNP in the form of AgNP@collagen altered the dynamics of dye triplet deactivation, effectively preventing the dye degradation and reducing the extent of protein crosslinked. Both crosslinked rHC and AgNP@collagen were able to support fibroblasts proliferation, but only the material containing silver was resistant to S. epidermidis infection.

  • 116.
    Suuronen, E.J.
    et al.
    Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Canada.
    Muzakare, L.
    Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
    Doillon, C.J.
    Oncology and Molecular Endocrinology Research Center CHUL and Laval University, Quebec City, Canada.
    Kapila, V.
    Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Canada.
    Li, F.
    University of Ottawa Eye Institute, University of Ottawa, Ottawa, Canada.
    Ruel, M.
    Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Canada.
    Griffith, M.
    Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
    Promotion of angiogenesis in tissue engineering: Developing multicellular matrices with multiple capacities2006Ingår i: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 29, nr 12, s. 1148-1157Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    One of the aims of tissue engineering is to be able to develop multi-tissue organs in the future. This requires the optimization of conditions for the differentiation of multiple cell types and maintenance of the differentiated phenotype within complex engineered tissues. The goal of this study was to develop prototype tissue engineered matrices to support the simultaneous growth of different cell types with a particular focus on the angiogenic process. We examined two different matrix compositions for the promotion of blood vessel and tube formation. A fibrin-based matrix with the addition of a combination of growth factors supported vascular growth and the invasion of inflammatory cells. Using this fibrin matrix, in combination with a collagen-based hydrogel, a simple in vitro model of the cornea with adjacent sclera was developed that was complete with innervation and vascular structures. In addition, we showed that collagen-based matrices were effective in delivering mononuclear endothelial progenitor cells to ischemic tissue in vivo, and allowing these cells to incorporate into vascular structures. It is anticipated that with further development, these matrices have potential for use as delivery matrices for cell transplantation and for in vitro study purposes of multiple cell types.

  • 117.
    Suuronen, Erik J.
    et al.
    University of Ottawa Eye Institute, Ottawa Health Research Institute—Vision Centre, and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
    McLaughlin, Christopher R.
    University of Ottawa Eye Institute, Ottawa Health Research Institute—Vision Centre, and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
    Stys, Peter K.
    Ottawa Health Research Institute — Division of Neuroscience, University of Ottawa, Ottawa, ON, Canada.
    Nakamura, Masatsugu
    Santen Pharmaceutical Company Ltd., Ikoma-shi, Nara,, Japan.
    Munger, Rejean
    University of Ottawa Eye Institute, Ottawa Health Research Institute—Vision Centre, and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
    Griffith, May
    University of Ottawa Eye Institute, Ottawa Health Research Institute—Vision Centre, and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
    Functional innervation in tissue engineered models for in vitro study and testing purposes2004Ingår i: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 82, nr 2, s. 525-533Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The biotechnology industry is rapidly expanding and the emerging field of tissue engineering is projected to have a high impact in the near future. Recently the field of cellular, drug, and prosthetic delivery has melded with the field of tissue engineering to make simulated tissues. In addition to their roles as tissue substitutes for transplantation, these simulated tissues may provide more accurate models and environments for toxicology testing and the study of peripheral nerves. The current study demonstrates the importance of innervation, in general, for the function of engineered tissues. We observe that the presence of nerves in a tissue engineered (TE) human cornea model enhances the growth of the epithelium and the formation of its protective mucin layer. Innervation also confers protection to the epithelium from chemical insult, as determined by the level of post-treatment epithelial cell death. We demonstrate differential responses of the nerves to chemical stimuli by changes in intracellular sodium as measured by 2-photon microscopy. The 2-photon imaging techniques also allow for the visualization and study of the fine sensory axon fibers within the 3-dimensional tissue. This work demonstrates a role for innervation in the protective quality and function of the engineered tissue, and the potential to use the nerves themselves as indicators of the severity of an insult. These results are important to consider for the development of any optimized TE models for in vitro study and testing purposes.

  • 118.
    Suuronen, Erik J.
    et al.
    University of Ottawa Eye Institute, Ottawa Health Research Institute-Vision Centre, and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
    Nakamura, Masatsugu
    Santen Pharmaceutical Company Ltd., Ikoma-shi, Nara, Japan.
    Watsky, Mitchell A.
    Department of Physiology, University of Tennessee Health Science Centre, Memphis, Tennessee, USA.
    Stys, Peter K.
    Ottawa Health Research Institute, Division of Neuroscience, University of Ottawa, Ottawa, Canada;.
    Muller, Linda J.
    Department of Morphology, The Netherlands Ophthalmic Research Institute, Amsterdam, The Netherlands.
    Munger, Rejean E.
    Tokyo Dental College-Ichikawa General Hospital Cornea Centre, Ichikawa, Chiba, Japan.
    Shinozaki, Naoshi
    Tokyo Dental College-Ichikawa General Hospital Cornea Centre, Ichikawa, Chiba, Japan.
    Griffith, May
    University of Ottawa Eye Institute, Ottawa Health Research Institute-Vision Centre, and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
    Innervated human corneal equivalents as in vitro models for nerve-target cell interactions2003Ingår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 17, s. 170-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A sensory nerve supply is crucial for optimal tissue function. However, the mechanisms for successful innervation and the signaling pathways between nerves and their target tissue are not fully understood. Engineered tissue substitutes can provide controllable environments in which to study tissue innervation. We have therefore engineered human corneal substitutes that promote nerve in-growth in a pattern similar to in vivo re-innervation. We demonstrate that these nerves (a) are morphologically equivalent to natural corneal nerves; (b) make appropriate contact with target cells; (c) can generate action potentials; (d) respond to chemical and physical stimuli; and (e) play an important role in the overall functioning of the bioengineered tissue. This model can be used for studying the more general topics of nerve ingrowth or regeneration and the interaction between nerves and their target cells and, more specifically, the role of nerves in corneal function. This model could also be used as an in vitro alternative to animals for safety and efficacy testing of chemicals and drugs.

  • 119.
    Suuronen, Erik J.
    et al.
    Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
    Sheardown, Heather
    Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada.
    Newman, Kimberley D.
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    McLaughlin, Christopher R.
    Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada and University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Griffith, May
    Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada and University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Building in vitro models of organs2005Ingår i: INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 244, Vol. 244, s. 137-173Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Tissue-engineering techniques are being used to build in vitro models of organs as substitutes for human donor organs for transplantation as well as in vitro toxicology testing (as alternatives to use of animals). Tissue engineering involves the fabrication of scaffolds from materials that are biologically compatible to serve as cellular supports and microhabitats in order to reconstitute a desired tissue or organ. Three organ systems that are currently the foci of tissue engineering efforts for both transplantation and in vitro toxicology testing purposes are discussed. These are models of the cornea, nerves (peripheral nerves specifically), and cardiovascular components. In each of these organ systems, a variety of techniques and materials are being used to achieve the same end results. In general, models that are designed with consideration of the developmental and cellular biology of the target tissues or organs have tended to result in morphologically and physiologically accurate models. Many of the models, with further development and refinement, have the potential to be useful as functional substitute tissues and organs for transplantation or for in vitro toxicology testing.

  • 120.
    Suuronen, Erik J.
    et al.
    Division of Cardiac Surgery, University of Ottawa, Ottawa, Ontario, Canada.
    Veinot, John P.
    Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario, Canada.
    Wong, Serena
    Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
    Kapila, Varun
    Division of Cardiac Surgery, University of Ottawa, Ottawa, Ontario, Canada.
    Price, Joel
    Division of Cardiac Surgery, University of Ottawa, Ottawa, Ontario, Canada.
    Griffith, May
    Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
    Mesana, Thierry G.
    Division of Cardiac Surgery, University of Ottawa, Ottawa, Ontario, Canada.
    Ruel, Marc
    Division of Cardiac Surgery and Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
    Tissue-engineered injectable collagen-based matrices for improved cell delivery and vascularization of ischemic tissue using CD133+progenitors expanded from the peripheral blood2006Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 114, s. I138-I144Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background-The use of stem and/or progenitor cells to achieve potent vasculogenesis in humans has been hindered by low cell numbers, implant capacity, and survival. This study investigated the expansion of CD133(+) cells and the use of an injectable collagen-based tissue engineered matrix to support cell delivery and implantation within target ischemic tissue. Methods and Results-Adult human CD133(+) progenitor cells from the peripheral blood were generated and expanded by successive removal and culture of CD133(-) cell fractions, and delivered within an injectable collagen-based matrix into the ischemic hindlimb of athymic rats. Controls received injections of phosphate-buffered saline, matrix, or CD133(+) cells alone. Immunohistochemistry of hindlimb muscle 2 weeks after treatment revealed that the number of CD133(+) cells retained within the target site was greater than 2-fold greater when delivered by matrix than when delivered alone (P less than 0.01). The transplanted CD133(+) cells incorporated into vascular structures, and the matrix itself also was vascularized. Rats that received matrix and CD133(+) cells demonstrated greater intramuscular arteriole and capillary density than other treatment groups (P less than 0.05 and P less than 0.01, respectively). Conclusions-Compared with other experimental approaches, treatment of ischemic muscle tissue with generated CD133(+) progenitor cells delivered in an injectable collagen-based matrix significantly improved the restoration of a vascular network. This work demonstrates a novel approach for the expansion and delivery of blood CD133(+) cells with resultant improvement of their implantation and vasculogenic capacity.

  • 121.
    Tengdelius, Mattias
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Cheung, Kitt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Univ Montreal, Canada; Univ Montreal, Canada.
    Påhlsson, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Improved antiviral properties of chain end lipophilic fucoidan-mimetic glycopolymers synthesized by RAFT polymerization2018Ingår i: European Polymer Journal, ISSN 0014-3057, E-ISSN 1873-1945, Vol. 98, s. 285-294Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sulfated polysaccharides and synthetic glycopolymers are promising candidates as antiviral drugs but have failed in clinical trials most likely due to lack of virucidal activity. However, studies have shown that incorporation of lipophilic end groups to oligosaccharide chains is a mean to gain the desired virucidal properties. Here, we describe the introduction of lipophilic end groups to sulfated alpha-L-fucoside-pendant polymethacrylamides, also known as fucoidan-mimetic glycopolymers, by RAFT polymerization. RAFT agents bearing octadecyl, dioctadecyl and cholesteryl groups were used to synthesize lipoglycopolymers of different chain lengths. Short lipoglycopolymers bearing lipophilic end groups showed an improved ability to block viral entry and infection of cells compared to glycopolymers without lipophilic end groups. Short lipoglycopolymers bearing octadecyl or dioctadecyl end groups, also completely stopped the spreading of the viral infection. However, these lipoglycopolymers did not show actual virucidal properties. Nevertheless, we have described a first step towards obtaining virucidal synthetic glycopolymers for clinical use.

  • 122.
    Tengdelius, Mattias
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Gurav, Deepanjali
    Uppsala University, Sweden; Savitri Bai Phule Pune University, India.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Påhlsson, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Oommen, Oommen P.
    Uppsala University, Sweden.
    Synthesis and anticancer properties of fucoidan-mimetic glycopolymer coated gold nanoparticles2015Ingår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 51, nr 40, s. 8532-8535Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Gold nanoparticles coated with fucoidan-mimetic glycopolymers were synthesized that displayed good colloidal stability and promising anti-cancer properties. Fucoidan mimetic glycopolymers on their own were nontoxic, while glycopolymer coated gold nanoparticles displayed selective cytotoxicity to human colon cancer cell lines (HCT116) while it was non-toxic to mouse fibroblast cells (NIH3T3).

  • 123.
    Tengdelius, Mattias
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Kardeby, Caroline
    University of Örebro, Sweden.
    Falker, Knut
    University of Örebro, Sweden.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Påhlsson, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Grenegard, Magnus
    University of Örebro, Sweden.
    Fucoidan-Mimetic Glycopolymers as Tools for Studying Molecular and Cellular Responses in Human Blood Platelets2017Ingår i: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195, Vol. 17, nr 2, artikel-id UNSP 1600257Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The marine sulfated polysaccharide fucoidan displays superior ability to induce platelet aggregation compared to other sulfated polysaccharides. As such, it is an attractive tool for studying molecular and cellular responses in activated platelets. The heterogeneous structure, however, poses a problem in such applications. This study describes the synthesis of sulfated alpha-L-fucoside-pendant poly(methacryl amides) with homogeneous structures. By using both thiol-mediated chain transfer and reversible addition-fragmentation chain transfer polymerization techniques, glycopolymers with different chain lengths are obtained. These glycopolymers show platelet aggregation response and surface changes similar to those of fucoidan, and cause platelet activation through intracellular signaling as shown by extensive protein tyrosine phosphorylation. As the platelet activating properties of the glycopolymers strongly mimic those of fucoidan, this study concludes these fucoidan-mimetic glycopolymers are unique tools for studying molecular and cellular responses in human blood platelets.

  • 124.
    Tengdelius, Mattias
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Lee, Chyan-Jang
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Grenegård, Magnus
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Påhlsson, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Synthesis and biological evaluation of fucoidan-mimetic glycopolymers through cyanoxyl-mediated free-radical polymerization2014Ingår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 15, nr 7, s. 2359-2368Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The sulfated marine polysaccharide fucoidan has been reported to have health benefits ranging from antivirus and anticancer properties to modulation of high blood pressure. Hence, they could enhance the biological function of materials for biomedical applications. However, the incorporation of fucoidan into biomaterials has been difficult, possibly due to its complex structure and lack of suitable functional groups for covalent anchoring to biomaterials. We have developed an approach for a rapid synthesis of fucoidanmimetic glycopolymer chains through cyanoxyl-mediated free-radical polymerization, a method suitable for chain-end functionalizing and subsequent linkage to biomaterials. The resulting sulfated and nonsulfated methacrylamido alpha-L-fucoside glycopolymers fucoidan-mimetic properties were studied in HSV-1 infection and platelet activation assays. The sulfated glycopolymer showed similar properties to natural fucoidan in inducing platelet activation and inhibiting HSV-1 binding and entry to cells, thus indicating successful syntheses of fucoidan-mimetic glycopolymers.

  • 125.
    Vignoni, Mariana
    et al.
    University of Ottawa, Canada.
    de Alwis Weerasekera, Hasitha
    University of Ottawa, Canada .
    Simpson, Madeline J.
    University of Ottawa, Canada .
    Phopase, Jaywant
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska högskolan.
    Mah, Thien-Fah
    University of Ottawa, Canada .
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Alarcon, Emilio I.
    University of Ottawa, Canada .
    Scaiano, Juan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    LL37 peptide@silver nanoparticles: combining the best of the two worlds for skin infection control2014Ingår i: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 6, nr 11, s. 5725-5728Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Capping silver nanoparticles with LL37 peptide eradicates the anti-proliferative effect of silver on primary skin cells, but retains the bactericidal properties of silver nanoparticles with activities comparable to silver nitrate or silver sulfadiazine. In addition, LL37 capped silver nanoparticles have anti-biofilm formation activity.

  • 126.
    Wand, Kerstin
    et al.
    Technical University of Munich, Germany.
    Neuhann, Raphael
    Technical University of Munich, Germany.
    Ullmann, Andrea
    Technical University of Munich, Germany.
    Plank, Katharina
    Technical University of Munich, Germany.
    Baumann, Michael
    MLase AG, Germany.
    Ritter, Roland
    Technolas PV Bausch and Lomb, Germany.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Lohmann, Chris P.
    Technical University of Munich, Germany.
    Kobuch, Karin
    Technical University of Munich, Germany.
    Riboflavin-UV-A Crosslinking for Fixation of Biosynthetic Corneal Collagen Implants2015Ingår i: Cornea, ISSN 0277-3740, E-ISSN 1536-4798, Vol. 34, nr 5, s. 544-549Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To evaluate riboflavin-UV-A crosslinking as an alternative suture-free fixation method for biosynthetic corneal collagen implants. Methods: A range of cell-free corneal implants consisting of recombinant human collagen type III were examined. In vitro, the implants were crosslinked with different riboflavin solutions and irradiations. Ex vivo, the biosynthetic corneal implants were placed on the anterior cornea of porcine and rabbit eyes after performing deep anterior lamellar keratoplasty with a trephine, femtosecond laser, or excimer laser. UV-A crosslinking was performed with isotonic or hypotonic riboflavin at either standard or rapid procedure. The corneas were excised, fixed in PFA 4%, and embedded in paraffin. Crosslinking effects on the implants and the adhesion between implant and corneal bed were evaluated by slit-lamp biomicroscopy, optical coherence tomography (OCT) images, and histologically. Results: After the crosslinking procedure, the implants showed different degrees of thinning. The accuracy of cutting the corneal bed was highest with the excimer laser. Good adhesion of the implant in the corneal bed could be demonstrated in OCT images. This was more accurate in porcine eyes than in rabbit eyes. Histologically, crosslinks between implant and corneal stroma were demonstrated. There was no difference between standard and rapid crosslinking procedures. Conclusions: Riboflavin-UV-A crosslinking as a fixation method for biosynthetic corneal collagen implants was demonstrated to be promising. It can reduce suture-related complications such as haze formation and surface irregularity. Stability of the implants, especially shrinkage after riboflavin-UV-A crosslinking, needs to be further evaluated. Biostability, integration, and long-term outcome are further evaluated in in vivo animal experiments.

  • 127.
    Wickham, Abeni M.
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska högskolan.
    Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Karolinska Institutet, Stockholm, Sweden.
    Mondal, Debasish
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Phopase, Jaywant
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska högskolan.
    Sadhu, Veera
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Tamás, Éva
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Thorax-kärlkliniken i Östergötland.
    Polisetti, Naresh
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Richter-Dahlfors, Agneta
    Karolinska Institutet, Stockholm, Sweden.
    Liedberg, Bo
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska högskolan. Nanyang Technological University, Singapore.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Karolinska Institutet, Stockholm, Sweden.
    Polycaprolactone–thiophene-conjugated carbon nanotube meshes as scaffolds for cardiac progenitor cells2014Ingår i: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981, Vol. 102, nr 7, s. 1553-1561Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The myocardium is unable to regenerate itself after infarct, resulting in scarring and thinning of the heart wall. Our objective was to develop a patch to buttress and bypass the scarred area, while allowing regeneration by incorporated cardiac stem/progenitor cells (CPCs). Polycaprolactone (PCL) was fabricated as both sheets by solvent casting, and fibrous meshes by electrospinning, as potential patches, to determine the role of topology in proliferation and phenotypic changes to the CPCs. Thiophene-conjugated carbon nanotubes (T-CNTs) were incorporated to enhance the mechanical strength. We showed that freshly isolated CPCs from murine hearts neither attached nor spread on the PCL sheets, both with and without T-CNT. As electrospun meshes, however, both PCL and PCL/T-CNT supported CPC adhesion, proliferation, and differentiation. The incorporation of T-CNT into PCL resulted in a significant increase in mechanical strength but no morphological changes to the meshes. In turn, proliferation, but not differentiation, of CPCs into cardiomyocytes was enhanced in T-CNT containing meshes. We have shown that changing the topology of PCL, a known hydrophobic material, dramatically altered its properties, in this case, allowing CPCs to survive and differentiate. With further development, PCL/T-CNT meshes or similar patches may become a viable strategy to aid restoration of the postmyocardial infarction myocardium.

  • 128.
    Zhang, Peng
    et al.
    School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, China.
    Yang, Jianhai
    School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, China.
    Li, Wenchen
    School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, China.
    Wang, Wei
    School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, China.
    Liu, Changjun
    School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, China.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Linköpings universitet, Hälsouniversitetet.
    Liu, Wenguang
    School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, China.
    Cationic polymer brush grafted-nanodiamond via atom transfer radical polymerization for enhanced gene delivery and bioimaging2011Ingår i: JOURNAL OF MATERIALS CHEMISTRY, ISSN 0959-9428, Vol. 21, nr 21, s. 7755-7764Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A novel cationic nanodiamond-polymer brush was synthesized by 2-bromoisobutyrate-modified nanodiamond (ND) surface-initiated atomic transfer radical polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA). Elemental analysis, FTIR, HRTEM, TGA and zeta potential analysis were used to confirm the successful synthesis of ND-polymer brushes. It was shown that the ND-brushes were capable of condensing plasmid DNA into stable nanoparticles, protecting DNA from enzyme degradation. Transfection studies demonstrated that the ND-brushes could not only efficiently deliver plasmids into COS-7 cells, but also mediate higher expression than PEI25k with lower cytotoxicity. The green fluorescence of ND-brushes could also be detected by laser scanning confocal microscopy, making the nanodiamond-polymer brushes an excellent multifunctional gene vector with not only high transfection efficiency but allowing for bioimaging.

123 101 - 128 av 128
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