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  • 51.
    Jangamreddy, Jaganmohan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. LV Prasad Eye Inst, India.
    Haagdorens, Michel K. C.
    Antwerp Univ Hosp, Belgium; Univ Antwerp, Belgium.
    Mirazul Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Lewis, Philip
    Cardiff Univ, Wales.
    Samanta, Ayan
    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.
    Liszka, Aneta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Kozak Ljunggren, Monika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Buznyk, Oleksiy
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Alarcon, Emilio I.
    Univ Ottawa, Canada.
    Zakaria, Nadia
    Antwerp Univ Hosp, Belgium; Univ Antwerp, Belgium.
    Meek, Keith M.
    Cardiff Univ, Wales.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Univ Montreal, Canada; Univ Montreal, Canada.
    Short peptide analogs as alternatives to collagen in pro-regenerative corneal implants2018Ingår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 69, s. 120-130Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Short collagen-like peptides (CLPs) are being proposed as alternatives to full-length collagen for use in tissue engineering, on their own as soft hydrogels, or conjugated to synthetic polymer for mechanical strength. However, despite intended clinical use, little is known about their safety and efficacy, mechanism of action or degree of similarity to the full-length counterparts they mimic. Here, we show the functional equivalence of a CLP conjugated to polyethylene glycol (CLP-PEG) to full-length recombinant human collagen in vitro and in promoting stable regeneration of corneal tissue and nerves in a pre- clinicalmini-pig model. We also show that these peptide analogs exerted their pro-regeneration effects through stimulating extracellular vesicle production by host cells. Our results support future use of CLP-PEG implants for corneal regeneration, suggesting the feasibility of these or similar peptide analogs in clinical application in the eye and other tissues. Statement of significance Although biomaterials comprising full-length recombinant human collagen and extracted animal collagen have been evaluated and used clinically, these macromolecules provide only a limited number of functional groups amenable to chemical modification or crosslinking and are demanding to process. Synthetic, customizable analogs that are functionally equivalent, and can be readily scaled-up are therefore very desirable for pre-clinical to clinical translation. Here, we demonstrate, using cornea regeneration as our test bed, that collagen-like-peptides conjugated to multifunctional polyethylene glycol (CLP-PEG) when grafted into mini-pigs as corneal implants were functionally equivalent to recombinant human collagen-based implants that were successfully tested in patients. We also show for the first time that these materials affected regeneration through stimulation of extracellular vesicle production by endogenous host cells that have migrated into the CLP-PEG scaffolds. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd.

  • 52.
    Jangamreddy, Jaganmohan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Haagdorens, Michel K. C.
    Antwerp Univ Hosp, Belgium; Univ Antwerp, Belgium.
    Mirazul Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Lewis, Philip
    Cardiff Univ, Wales.
    Samanta, Ayan
    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.
    Liszka, Aneta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Kozak Ljunggren, Monika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Buznyk, Oleksiy
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Alarcon, Emilio I.
    Univ Ottawa Heart Inst, Canada.
    Zakaria, Nadia
    Antwerp Univ Hosp, Belgium; Univ Antwerp, Belgium.
    Meek, Keith M.
    Univ Ottawa Heart Inst, Canada.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Univ Montreal, Canada; Univ Montreal, Canada.
    Short peptide analogs as alternatives to collagen in pro-regenerative corneal implants (vol 69, pg 120, 2018)2019Ingår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 88, s. 556-557Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    n/a

  • 53.
    Kamolz, Lars-Peter
    et al.
    Medical University of Graz, Austria.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Finnerty, Celeste
    University of Texas Medical Branch, TX 77555 USA.
    Kasper, Cornelia
    University of Nat Resources and Life Science, Austria.
    Editorial Material: Skin Regeneration, Repair, and Reconstruction in BIOMED RESEARCH INTERNATIONAL, vol , issue 892031, pp2015Ingår i: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, Vol. 2015, s. 1-, artikel-id 892031Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 54.
    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.

  • 55.
    Koh, Li Buay
    et al.
    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, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Swedish Nanoscience Center, Karolinska Institute, Stockholm , Sweden .
    Mitra, Debbie
    Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
    Noel, Christopher
    Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
    Merett, Kimberley
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
    Odorcic, Silvia
    Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Ögonkliniken US/LiM.
    Jackson, William Bruce
    Ottawa Hospital Research Institute, University of Ottawa Eye Institute, ON, Canada.
    Liedberg, Bo
    Center for Biomimetic Sensor Science, Nanyang Technological University, Singapore.
    Phopase, Jaywant
    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. Swedish Nanoscience Center, Karolinska Institute, Stockholm, Sweden.
    Epoxy Cross-Linked Collagen and Collagen-Laminin Peptide Hydrogels as Corneal Substitutes2013Ingår i: Journal of Functional Biomaterials, ISSN 2079-4983, E-ISSN 2079-4983, Vol. 4, nr 3, s. 162-177Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A bi-functional epoxy-based cross-linker, 1,4-Butanediol diglycidyl ether (BDDGE), was investigated in the fabrication of collagen based corneal substitutes. Two synthetic strategies were explored in the preparation of the cross-linked collagen scaffolds. The lysine residues of Type 1 porcine collagen were directly cross-linked using l,4-Butanediol diglycidyl ether (BDDGE) under basic conditions at pH 11. Alternatively, under conventional methodology, using both BDDGE and 1-Ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) as cross-linkers, hydrogels were fabricated under acidic conditions. In this latter strategy, Cu(BF4)2·XH2O was used to catalyze the formation of secondary amine bonds. To date, we have demonstrated that both methods of chemical cross-linking improved the elasticity and tensile strength of the collagen implants. Differential scanning calorimetry and biocompatibility studies indicate comparable, and in some cases, enhanced properties compared to that of the EDC/NHS controls. In vitro studies showed that human corneal epithelial cells and neuronal progenitor cell lines proliferated on these hydrogels. In addition, improvement of cell proliferation on the surfaces of the materials was observed when neurite promoting laminin epitope, IKVAV, and adhesion peptide, YIGSR, were incorporated. However, the elasticity decreased with peptide incorporation and will require further optimization. Nevertheless, we have shown that epoxy cross-linkers should be further explored in the fabrication of collagen-based hydrogels, as alternatives to or in conjunction with carbodiimide cross-linkers.

  • 56.
    Kozak Ljunggren, Monika
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Elizondo, Rodolfo A.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Edin, Joel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Olsen, David
    FibroGen Incorporated, San Francisco, CA, USA.
    Merrett, Kimberley
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet. Ottawa Hospital Research Institute–Vision Programme, Ottawa, Ontario, Canada.
    Lee, Chang-Jang
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. Ottawa Hospital Research Institute–Vision Programme, Ottawa, Ontario, Canada.
    Salerud, Göran
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Polarek, James
    FibroGen Incorporated, San Francisco, CA, USA.
    Fagerholm, Per
    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.
    Effect of Surgical Technique on Corneal Implant Performance2014Ingår i: Translational Vision Science & Technology, ISSN 2164-2591, Vol. 3, nr 2, s. 1-13Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Our aim was to determine the effect of a surgical technique on biomaterial implant performance, specifically graft retention.

     

    Methods: Twelve mini pigs were implanted with cell-free, 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) cross-linked recombinant human collagen type III (RHCIII) hydrogels as substitutes for donor corneal allografts using overlying sutures with or without human amniotic membrane (HAM) versus interrupted sutures with HAM. The effects of the retention method were compared as well as the effects of collagen concentration (13.7% to 15% RHCIII).

    Results: All implanted corneas showed initial haze that cleared with time, resulting in corneas with optical clarity matching those of untreated controls. Biochemical analysis showed that by 12 months post operation, the initial RHCIII implants had been completely remodeled, as type I collagen, was the major collagenous protein detected, whereas no RHCIII could be detected. Histological analysis showed all implanted corneas exhibited regeneration of epithelial and stromal layers as well as nerves, along with touch sensitivity and tear production. Most neovascularization was seen in corneas stabilized by interrupted sutures.

    Conclusions: This showed that the surgical technique used does have a significant effect on the overall performance of corneal implants, overlying sutures caused less vascularization than interrupted sutures.

    Translational Relevance: Understanding the significance of the suturing technique can aid the selection of the most appropriate procedure when implanting artificial corneal substitutes. The same degree of regeneration, despite a higher collagen content indicates that future material development can progress toward stronger, more resistant implants.

  • 57.
    Kozak Ljunggren, Monika
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Animal models ad in vitro alternatives in regenerative medicine: Focus on biomaterials development2014Ingår i: Innovative Strategies in Tissue Engineering / [ed] Mayuri S. Prasad & Paolo Di Nardo, Aalborg, Denmark: River Publishers, 2014, s. 37-51Kapitel i bok, del av antologi (Övrigt vetenskapligt)
  • 58.
    Krishna Tummala, Gopi
    et al.
    Uppsala University, Sweden.
    Joffre, Thomas
    Uppsala University, Sweden.
    Lopes, Viviana R.
    Uppsala University, Sweden.
    Liszka, Aneta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Buznyk, Oleksiy
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. NAMS Ukraine, Ukraine.
    Ferraz, Natalia
    Uppsala University, Sweden.
    Persson, Cecilia
    Uppsala University, Sweden.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Mihranyan, Albert
    Uppsala University, Sweden.
    Hyperelastic Nanocellulose-Reinforced Hydrogel of High Water Content for Ophthalmic Applications2016Ingår i: ACS BIOMATERIALS SCIENCE and ENGINEERING, ISSN 2373-9878, Vol. 2, nr 11, s. 2072-2079Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A nanocellulose-reinforced poly(vinyl alcohol) hydrogel material of exceptionally high water content for ophthalmic applications is presented (amp;gt;90 wt %), which also features a hitherto unprecedented combination of optical, mechanical, viscoelastic, oxygen permeability, and biocompatibility properties. The hydrogel combines the desired softness with remarkable strain-dependent mechanical strength and thereby demonstrates hyperelastic, rubber-like mechanical properties. The observed unusual mechanical behavior is due to both high water content and the combination of relatively stiff cellulose nanowhiskers entangled in a soft polymer matrix of poly(vinyl alcohol) (PVA), thus mimicking the structural characteristics of the corneas main constituents, i.e., water and collagen.

  • 59.
    Kuraitis, D
    et al.
    University of Ottawa.
    Zhang, P
    University of Ottawa.
    Zhang, Y
    University of Ottawa.
    Padavan, D T
    University of Ottawa.
    McEwan, K
    University of Ottawa.
    Sofrenovic, T
    University of Ottawa.
    McKee, D
    University of Ottawa.
    Zhang, J
    University of Western Ontario.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Linköpings universitet, Hälsouniversitetet.
    Cao, X
    University of Ottawa.
    Musaro, A
    University of Roma La Sapienza.
    Ruel, M
    University of Ottawa.
    Suuronen, J
    University of Ottawa.
    A STROMAL CELL-DERIVED FACTOR-1 RELEASING MATRIX ENHANCES THE PROGENITOR CELL RESPONSE AND BLOOD VESSEL GROWTH IN ISCHAEMIC SKELETAL MUSCLE2011Ingår i: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, Vol. 22, s. 109-123Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Although many regenerative cell therapies are being developed to replace or regenerate ischaemic muscle, the lack of vasculature and poor persistence of the therapeutic cells represent major limiting factors to successful tissue restoration. In response to ischaemia, stromal cell-derived factor-1 (SDF-1) is up-regulated by the affected tissue to stimulate stem cell-mediated regenerative responses. Therefore, we encapsulated SDF-1 into alginate microspheres and further incorporated these into an injectable collagen-based matrix in order to improve local delivery. Microsphere-matrix impregnation reduced the time for matrix thermogelation, and also increased the viscosity reached. This double-incorporation prolonged the release of SDF-1, which maintained adhesive and migratory bioactivity, attributed to chemotaxis in response to SDF-1. In vivo, treatment of ischaemic hindlimb muscle with microsphere-matrix led to increased mobilisation of bone marrow-derived progenitor cells, and also improved recruitment of angiogenic cells expressing the SDF-1 receptor (CXCR4) from bone marrow and local tissues. Both matrix and SDF-1-releasing matrix were successful at restoring perfusion, but SDF-1 treatment appeared to play an earlier role, as evidenced by arterioles that are phenotypically older and by increased angiogenic cytokine production, stimulating the generation of a qualitative microenvironment for a rapid and therefore more efficient regeneration. These results support the release of implanted SDF-1 as a promising method for enhancing progenitor cell responses and restoring perfusion to ischaemic tissues via neovascularisation.

  • 60.
    Lagali, Neil
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmiatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmiatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmiatrik. Linköpings universitet, Hälsouniversitetet.
    Editorial Material: Biosynthetic corneas: prospects for supplementing the human donor cornea supply in EXPERT REVIEW OF MEDICAL DEVICES, vol 8, issue 2, pp 127-1302011Ingår i: Expert Review of Medical Devices, ISSN 1743-4440, E-ISSN 1745-2422, Vol. 8, nr 2, s. 127-130Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    n/a

  • 61.
    Lagali, Neil
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmiatrik. Linköpings universitet, Hälsouniversitetet.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Regenerativ medicin. Linköpings universitet, Hälsouniversitetet.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmiatrik. Linköpings universitet, Hälsouniversitetet.
    In vivo confocal microscopy of the cornea to assess tissue regenerative response after biomaterial implantation in humans.2013Ingår i: Corneal Regenerative Medicine: Methods and ProtocolsPart IV / [ed] Bernice Wright; Che J Connon, Humana Press, 2013, Vol. 1014, s. 211-23Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [en]

    Laser-scanning in vivo confocal microscopy (IVCM) of the cornea is becoming an increasingly popular tool to examine the living human cornea with cellular-level detail in both healthy and pathologic states. Here, we describe the use of the IVCM technique to examine the processes of tissue healing and regeneration in the living human eye after biomaterial implantation. The regenerative response can be assessed by performing longitudinal IVCM imaging of a laboratory-made, cell-free biomaterial, after direct implantation into a pathologic eye as a primary alternative to human donor tissue transplantation.

  • 62.
    Lagali, Neil
    et al.
    University of Ottawa Eye Institute.
    Griffith, May
    Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada.
    Fagerholm, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    Merrett, Kimberley
    University of Ottawa Eye Institute.
    Huynh, Melissa
    University of Ottawa Eye Institute.
    Munger, Rejean
    University of Ottawa Eye Institute.
    Innervation of tissue-engineered recombinant human collagen-based corneal substitutes: A comparative in vivo confocal microscopy study2008Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 49, nr 9, s. 3895-3902Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. To compare reinnervation in recombinant human collagen-based corneal substitutes with allografts during a 1-year postimplantation follow-up period in pigs. A retrospective comparison to innervation in porcine collagen-based biosynthetic grafts was also performed. METHODS. Pigs received a corneal allograft or a substitute made of either recombinant human type-I or -III collagen. In vivo confocal microscopic examination of the central cornea of surgical and untouched control eyes before surgery and at 2, 6, and 12 months after surgery was performed to quantify the number, density, and diameter of nerves at various corneal depths. RESULTS. By 12 months after surgery, the number and density of regenerated nerves in the anterior and deep anterior corneal stroma recovered to preoperative and control levels in both types of substitute grafts and in the allografts. In the subepithelial and subbasal regions, however, significantly fewer nerves were detected relative to those in control subjects at 12 months, regardless of graft type ( P < 0.05), similar to the behavior of porcine collagen-based biosynthetic grafts. An absence of thick stromal nerve trunks (diameter, > 10 mu m) in all grafts, irrespective of material type, indicated that nerve regeneration in grafts was accompanied by persistent morphologic changes. CONCLUSIONS. Nerve regeneration in recombinant human collagen-based biosynthetic corneal grafts proceeded similarly to that in allograft tissue, demonstrating the suitability of recombinant human collagen constructs as nerve-friendly corneal substitutes. Furthermore, only minor differences were noted between type-I and -III collagen grafts, indicating an insensitivity of nerve regeneration to initial collagen type.

  • 63.
    Lagali, N.S.
    et al.
    University of Ottawa Eye Institute, University of Ottawa, Ottawa, ON, Canada.
    Griffith, M.
    University of Ottawa Eye Institute, University of Ottawa, Ottawa, ON, Canada, Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
    Shinozaki, N.
    TDC Eye Bank and Cornea Centre, Ichikawa General Hospital, Chiba, Japan.
    Fagerholm, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    Munger, R.
    University of Ottawa Eye Institute, University of Ottawa, Ottawa, ON, Canada, University of Ottawa Eye Institute, Ottawa Hospital-General Campus, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada.
    Innervation of tissue-engineered corneal implants in a porcine model: A 1-year in vivo confocal microscopy study2007Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 48, nr 8, s. 3537-3544Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. To examine the pattern of nerve regeneration within tissue-engineered corneal substitutes grafted into host porcine corneas over a 1-year postoperative period. METHODS. Biodegradable corneal substitutes from cross-linked collagen were implanted into the left eyes of 12 pigs by deep lamellar keratoplasty. Regeneration of severed nerves into the central implant region was investigated with in vivo confocal microscopy. Both implant-recipient and control (right) eyes were examined before surgery and 2, 6, 10, and 12 months after surgery, to quantify the number, density, diameter, and branching of nerve fiber bundles at various corneal depths. Transmission electron microscopy was used to confirm the presence of nerve bundles. RESULTS. Two months after surgery, corneal nerve ingrowth was observed within the deep anterior stroma, with a number and density of regenerated nerves significantly higher than in nonsurgical control eyes (P < 0.01). Nerves within the superficial anterior stroma regenerated by 6 to 10 months after surgery, and the first subbasal epithelial nerves were seen 10 months after surgery. After 1 year, subbasal nerve density recovered to preoperative levels. Nerve fibers in the deep anterior stroma remained significantly thinner relative to control eyes after 1 year (P < 0.001), where both superficial anterior and subbasal nerve diameter did not change relative to control eyes. CONCLUSIONS. The pattern of reinnervation within tissue-engineered corneal substitutes has been quantified in vivo. Innervation proceeded rapidly in the deep anterior stroma, followed by repopulation of more superficial regions. One year after surgery, nerve density within the tissue-engineered cornea increased or remained unchanged relative to controls in all corneal regions examined. Copyright © Association for Research in Vision and Ophthalmology.

  • 64.
    Lee, Chyan-Jang
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Buznyk, Oleksiy
    Filatov Institute of Eye Diseases and Tissue Therapy, Odessa, Ukraine .
    Kuffova, Lucia
    University of Aberdeen, Scotland .
    Rajendran, Vijayalakshmi
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet. University of Aberdeen, Scotland.
    Forrester, John V.
    University of Aberdeen, Scotland.
    Phopase, Jaywant
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Skog, Mårten
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Ahlqvist, Jenny
    Vironova AB, Stockholm, Sweden.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Cathelicidin LL-37 and HSV-1 Corneal Infection: Peptide Versus Gene Therapy2014Ingår i: Translational Vision Science & Technology, ISSN 2164-2591, Vol. 3, nr 3, s. 1-14Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: To evaluate the potential utility of collagen-based corneal implants with anti?Herpes Simplex Virus (HSV)-1 activity achieved through sustained release of LL-37, from incorporated nanoparticles, as compared with cell-based delivery from model human corneal epithelial cells (HCECs) transfected to produce endogenous LL-37. Methods: We tested the ability of collagen-phosphorylcholine implants to tolerate the adverse microenvironment of herpetic murine corneas. Then, we investigated the efficacy of LL-37 peptides delivered through nanoparticles incorporated within the corneal implants to block HSV-1 viral activity. In addition, LL-37 complementary DNA (cDNA) was transferred into HCECs to confer viral resistance, and their response to HSV-1 infection was examined. Results: Our implants remained in herpetic murine corneas 7 days longer than allografts. LL-37 released from the implants blocked HSV-1 infection of HCECs by interfering with viral binding. However, in pre-infected HCECs, LL-37 delayed but could not prevent viral spreading nor clear viruses from the infected cells. HCECs transfected with the LL-37 expressed and secreted the peptide. Secreted LL-37 inhibited viral binding in vitro but was insufficient to protect cells completely from HSV-1 infection. Nevertheless, secreted LL-37 reduced both the incidence of plaque formation and plaque size. Conclusion: LL-37 released from composite nanoparticle-hydrogel corneal implants and HCEC-produced peptide, both showed anti?HSV-1 activity by blocking binding. However, while both slowed down virus spread, neither was able on its own to completely inhibit the viruses. Translational Relevance: LL-37 releasing hydrogels may have potential utility as corneal substitutes for grafting in HSV-1 infected corneas, possibly in combination with LL-37 producing therapeutic cells.

  • 65.
    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.

  • 66.
    Li, Fengfu
    et al.
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Carlsson, David J.
    National Research Council Canada, Ottawa, Ontario Canada.
    Lohmann, Chris
    Universitäts-Augenklink, University of Regensburg, Regensburg, Germany.
    Bueckert, Donna
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Munger, Rejean
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Griffith, May
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Corneal implantation with collagen-copolymer matrices2005Ingår i: Key Engineering Materials, ISSN 1013-9826, E-ISSN 1662-9795, Vol. 288-289, s. 389-392Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A transparent matrix composed of collagen and poly(N, N-dimethylacrylamide-coacryloxysuccimide), 8mm in diameter and 350 mu m thick was implanted into pigs corneas using the lamellar keratoplasty (LKP) technique. No adverse immune or inflammatory reaction was observed during 4 month implantation period. Regenerated nerve filaments were observed in the subepithelial region and stroma by confacal microscopy. The endothelium of the operated eye was not touched by LKP and remained similar to that of the contra lateral (not operated) eye. The implant remained transparent over the four-month post-operative period, and clinical topography showed reconstitution of a smooth cornea surface. These preliminary results indicated that a new, functional cornea was re-established from the implanted biosynthetic matrix. This bio-synthetic matrix may have applications in other tissue engineering areas,, especially where innervation is important.

  • 67.
    Li, Fengfu
    et al.
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada and National Research Council, Ottawa, Ontario, Canada.
    Carlsson, David
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada and National Research Council, Ottawa, Ontario, Canada.
    Lohmann, Chris
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada and Universitäts-Augenklinik, University of Regensburg, Regensburg, Germany.
    Suuronen, Erik
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Vascotto, Sandy
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Kobuch, Karin
    Universitäts-Augenklinik, University of Regensburg, Regensburg, Germany.
    Sheardown, Heather
    Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada.
    Munger, Rejean
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Nakamura, Masatsugu
    Santen Pharmaceutical Company, Ltd., Ikoma-Shi, Japan .
    Griffith, May
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Cellular and nerve regeneration within a biosynthetic extracellular matrix for corneal transplantation2003Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 100, nr 26, s. 15346-15351Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Our objective was to determine whether key properties of extracellular matrix (ECM) macromolecules can be replicated within tissue-engineered biosynthetic matrices to influence cellular properties and behavior. To achieve this, hydrated collagen and N-isopropylacrylamide copolymer-based ECMs were fabricated and tested on a corneal model. The structural and immunological simplicity of the cornea and importance of its extensive innervation for optimal functioning makes it an ideal test model. In addition, corneal failure is a clinically significant problem. Matrices were therefore designed to have the optical clarity and the proper dimensions, curvature, and biomechanical properties for use as corneal tissue replacements in transplantation. In vitro studies demonstrated that grafting of the laminin adhesion pentapeptide motif, YIGSR, to the hydrogels promoted epithelial stratification and neurite in-growth. Implants into pigs corneas demonstrated successful in vivo regeneration of host corneal epithelium, stroma, and nerves. In particular, functional nerves were observed to rapidly regenerate in implants. By comparison, nerve regeneration in allograft controls was too slow to be observed during the experimental period, consistent with the behavior of human cornea transplants. Other corneal substitutes have been produced and tested, but here we report an implantable matrix that performs as a physiologically functional tissue substitute and not simply as a prosthetic device. These biosynthetic ECM replacements should have applicability to many areas of tissue engineering and regenerative medicine, especially where nerve function is required.

  • 68.
    Li, Fengfu
    et al.
    Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario K1H8L6, Canada / University of Ottawa Eye Institute, 501 Smyth Road, Ottawa, Ontario K1H8L6, Canada.
    Hurley, Bernard
    Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario K1H8L6, Canada / University of Ottawa Eye Institute, 501 Smyth Road, Ottawa, Ontario K1H8L6, Canada.
    Liu, Yun
    Centre for Catalysis Research and Innovation, and Department of Chemistry, University of Ottawa, 10 Marie Curie, Ottawa, Ontario K1N 6N5, Canada.
    Leonard, Brian
    Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario K1H8L6, Canada / University of Ottawa Eye Institute, 501 Smyth Road, Ottawa, Ontario K1H8L6, Canada.
    Griffith, May
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario K1H8L6, Canada / University of Ottawa Eye Institute, 501 Smyth Road, Ottawa, Ontario K1H8L6, Canada.
    Controlled release of bevacizumab through nanospheres for extended treatment of age-related macular degeneration.2012Ingår i: The open ophthalmology journal, ISSN 1874-3641, Vol. 6, s. 54-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bevacizumab (Avastin(®)) has been used by ophthalmologists in many countries as an off-label drug for the treatment of wet age-related macular degeneration (AMD). Due to its short half-life necessitating frequent intravitreal injection, a method for sustained delivery is in need. We demonstrated that bevacizumab could be released in a sustained fashion over 90 days from nano- and microspheres fabricated from poly(DL-lactide-co-glycolide) and poly(ethylene glycol)-b-poly(D,L-lactic acid), respectively. The drug release rate could be adjusted by alteration of the drug/polymer ratio. The use of such nano- and microspheres as bevacizumab delivery vehicles may improve the treatment of wet AMD.

  • 69.
    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.

  • 70.
    Liu, Wenguang
    et al.
    University of Ottawa.
    Deng, Chao
    University of Ottawa.
    McLaughlin, Christopher R
    University of Ottawa.
    Fagerholm, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    Lagali, Neil S
    University of Ottawa.
    Heyne, Belinda
    University of Ottawa.
    Scaiano, Juan C
    University of Ottawa.
    Watsky, Mitchell A
    University of Tennessee.
    Kato, Yasuhiro
    Tokyo Dental College.
    Munger, Rejean
    University of Ottawa.
    Shinozaki, Naoshi
    Tokyo Dental College.
    Li, Fengfu
    University of Ottawa.
    Griffith, May
    University of Ottawa.
    Collagen-phosphorylcholine interpenetrating network hydrogels as corneal substitutes2009Ingår i: BIOMATERIALS, ISSN 0142-9612, Vol. 30, nr 8, s. 1551-1559Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A biointeractive collagen-phospholipid corneal Substitute was fabricated from interpenetrating polymeric networks comprising 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide and N-hydroxysuccinimide crosslinked porcine atelocollagen, and poly(ethylene glycol) diacrylate crosslinked 2-methacryloyloxyethyl phosphorylcholine (MPC). The resulting hydrogels showed ail overall increase in mechanical strength beyond that of either original component and enhanced stability against enzymatic digestion (by collagenase) or UV degradation. More strikingly, these hydrogels retained the full biointeractive, cell friendly properties of collagen in promoting corneal cell and nerve in-growth and, regeneration (despite MPCs known anti-adhesive properties). Measurements of refractive indices, white light transmission and backscatter showed the optical properties of collagen-MPC are comparable or superior to those of the human cornea.In addition, the glucose and albumin permeability were comparable to those Of human corneas. Twelve-month post-implantation results of collagen-MPC hydrogels into mini-pigs showed regeneration of corneal tissue (epithelium, stroma) as well as the tear film and sensory nerves. We also show that porcine collagen can be Substituted with recombinant human collagen, resulting in a fully-synthetic implant that is free from the potential risks of disease transmission (e.g. prions) present in animal Source materials.

  • 71.
    Liu, Wenguang
    et al.
    Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
    Griffith, May
    Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.
    Li, Fengfu
    University of Ottawa Eye Institute and Ottawa Health Research Institute, Ottawa, ON, Canada.
    Alginate microsphere-collagen composite hydrogel for ocular drug delivery and implantation2008Ingår i: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 19, nr 11, s. 3365-3371Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A composite collagen hydrogel containing protein encapsulated alginate microspheres was developed for ocular applications. Bovine serum albumin (BSA) served as a drug model. The composite hydrogel retained optical clarity and mechanical robustness of control hydrogels without microspheres. A sustained release of BSA was achieved during an 11-day period in neutral phosphate buffer. The composite hydrogel supported human corneal epithelial cell growth and had adequate mechanical strength and excellent optical clarity for possible use as therapeutic lens for drug delivery and/or use as corneal substitute for transplantation into patients who have corneal diseases.

  • 72.
    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.

  • 73.
    Liu, Y
    et al.
    National Research Council Canada, Ottawa, Canada.
    Griffith, M
    University of Ottawa, Eye Institute, Ottawa, Canada.
    Watsky, MA
    University of Tennessee Health Center, Memphis, Tennessee.
    Forrester, JV
    University of Aberdeen, Department of Ophthalmology, Institute of Medical Science, Aberdeen, Scotland.
    Kuffova, L
    University of Aberdeen, Department of Ophthalmology, Institute of Medical Science, Aberdeen, Scotland.
    Grant, D
    University of Ottawa, Eye Institute, Ottawa, Canada.
    Merrett, K
    National Research Council Canada and University of Ottawa, Eye Institute, Ottawa, Canada.
    Carlsson, DJ
    University of Ottawa, Department of Ophthalmology, Ottawa, Canada.
    Properties of porcine and recombinant human collagen matrices for optically clear tissue engineering applications2006Ingår i: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 7, nr 6, s. 1819-1828Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Porcine and recombinant human atelocollagen I solutions were cross-linked with a water soluble carbodiimide at various stoichiometries and collagen concentrations (5-20 w/w %). The resulting hydrogels were clear and, when used as cell growth matrices, allowed cell and nerve visualization in vitro and in vivo. We have previously reported that, after six months of implantation in pigs and rabbits corneas, these robust hydrogels allowed regeneration of host cells and nerves to give optically clear corneas with no detected loss in thickness, indicating stable engraftment. Here, the biocompatible hydrogel formulations leading to this novel in vivo performance were characterized for amine consumption, gel hydration, thermal properties, optical clarity, refractive index, nutrient diffusion, biodegradation, tensile measurements, and average pore diameters. Gels with excellent in vitro (epithelial overgrowth, neurite penetration) and in vivo performance (clarity, touch sensitivity regeneration) had 4-11 nm pores, yet had glucose and albumin diffusive coefficients similar to mammalian corneas and allowed neurite extension through the gels.

  • 74. Liu, Yuwen
    et al.
    Gan, Lisha
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi.
    Carlsson, David J
    Fagerholm, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US.
    Lagali, Neil
    University of Ottawa.
    Watsky, Mitchell A
    Munger, Rejean
    Hodge, William G
    Priest, David
    Griffith, May
    A simple, cross-linked collagen tissue substitute for corneal implantation2006Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 47, nr 5, s. 1869-1875Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. To develop a simple corneal substitute from crosslinked collagen. METHODS. Porcine type I collagen (10%, pH 5), was mixed with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The final homogenous solution was molded to corneal dimensions, cured, and then implanted into rabbits and minipigs by lamellar keratoplasty. The implants were followed for up to 6 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, topography and esthesiometry for nerve function. Histopathologic examinations were also performed on rabbit corneas harvested after 6 months. RESULTS. Cross-linked collagen (refractive index, 1.35) had optical clarity superior to human corneas. Implanted into rabbit and porcine corneas, only 1 of 24 of the surgical corneas showed a slight haze at 6 months after surgery. All other implants showed no adverse reactions and remained optically clear. Topography showed a smooth surface and a profile similar to that of the contralateral nonsurgical eye. The implanted matrices promoted regeneration of corneal cells, tear film, and nerves. Touch sensitivity was restored, indicating some restoration of function. The corneas with implants showed no significant loss of thickness and demonstrated stable host- graft integration. CONCLUSIONS. Collagen can be adequately stabilized, using water soluble carbodiimides as protein cross-linking reagents, in the fabrication of corneal matrix substitutes for implantation. The simple cross-linking methodology would allow for easy fabrication of matrices for transplantation in centers where there is a shortage of corneas, or where there is need for temporary patches to repair perforations in emergency situations. Copyright © Association for Research in Vision and Ophthalmology.

  • 75.
    Mak, Wing Cheung
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska fakulteten.
    Cheung, K.Y.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Orban, Jenny
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska fakulteten.
    Lee, C-J
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska fakulteten.
    Turner, Anthony
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska fakulteten.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Theranostic Contact Lens for Modulation and Detection of Viral Infection2017Ingår i: 26th Anniversary World Congress on Biosensors (Biosensors), Elsevier, 2017Konferensbidrag (Övrigt vetenskapligt)
  • 76.
    Mak, Wing Cheung
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensor- och aktuatorsystem. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Magne, B.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Cheung, Kitt
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Atanasova, Diana
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. University of Montreal, Canada.
    Thermo-rheological responsive microcapsules for time-dependent controlled release of human mesenchymal stromal cells2017Ingår i: Biomaterials Science, ISSN 2047-4830, E-ISSN 2047-4849, Vol. 5, nr 11, s. 2241-2250Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human mesenchymal stromal cells (hMSCs) are adult-source cells that have been extensively evaluated for cell-based therapies. hMSCs delivered by intravascular injection have been reported to accumulate at the sites of injury to promote tissue repair and can also be employed as vectors for the delivery of therapeutic genes. However, the full potential of hMSCs remains limited as the cells are lost after injection due to anoikis and the adverse pathologic environment. Encapsulation of cells has been proposed as a means of increasing cell viability. However, controlling the release of therapeutic cells over time to target tissue still remains a challenge today. Here, we report the design and development of thermo-rheological responsive hydrogels that allow for precise, time dependent controlled-release of hMSCs. The encapsulated hMSCs retained good viability from 76% to 87% dependent upon the hydrogel compositions. We demonstrated the design of different blended hydrogel composites with modulated strength (S parameter) and looseness of hydrogel networks (N parameter) to control the release of hMSCs from thermoresponsive hydrogel capsules. We further showed the feasibility for controlled-release of encapsulated hMSCs within 3D matrix scaffolds. We reported for the first time by a systematic analysis that there is a direct correlation between the thermo-rheological properties associated with the degradation of the hydrogel composite and the cell release kinetics. This work therefore provides new insights into the further development of smart carrier systems for stem cell therapy.

  • 77.
    Mak, Wing Cheung
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Olesen, Kim
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Sivlér, Petter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Lee, Chyan-Jang
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Moreno- Jimenzen, Inés
    Southampton General Hospital, Southampton, Hampshire SO16 6YD, UK .
    Edin, Joel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Courtman, David
    Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada.
    Skog, Mårten
    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.
    Controlled delivery of human cells by temperature responsive microcapsules2015Ingår i: Journal of Functional Biomaterials, ISSN 2079-4983, E-ISSN 2079-4983, Vol. 6, nr 2, s. 439-453Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cell therapy is one of the most promising areas within regenerative medicine. However, its full potential is limited by the rapid loss of introduced therapeutic cells before their full effects can be exploited, due in part to anoikis, and in part to the adverse environments often found within the pathologic tissues that the cells have been grafted into. Encapsulation of individual cells has been proposed as a means of increasing cell viability. In this study, we developed a facile, high throughput method for creating temperature responsive microcapsules comprising agarose, gelatin and fibrinogen for delivery and subsequent controlled release of cells. We verified the hypothesis that composite capsules combining agarose and gelatin, which possess different phase transition temperatures from solid to liquid, facilitated the destabilization of the capsules for cell release. Cell encapsulation and controlled release was demonstrated using human fibroblasts as model cells, as well as a therapeutically relevant cell line—human umbilical vein endothelial cells (HUVECs). While such temperature responsive cell microcapsules promise effective, controlled release of potential therapeutic cells at physiological temperatures, further work will be needed to augment the composition of the microcapsules and optimize the numbers of cells per capsule prior to clinical evaluation.

  • 78.
    Mak, Wing Cheung
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensor- och aktuatorsystem. Linköpings universitet, Tekniska fakulteten.
    Olesen, Kim
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Sivlér, Petter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Lee, Chyan-Jang
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Moreno-Jimenez, Ines
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Bone & Joint Research Group, Stem Cells & Regeneration Institute of Developmental Sciences, Southampton General Hospital, UK.
    Edin, Joel
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Courtman, D.
    Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Canada.
    Skog, Mårten
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Correction: W.C. Mak, et al. Controlled Delivery of Human Cells by Temperature Responsive Microcapsules. J. Funct. Biomater. 2015, 6, 439-4532018Ingår i: Journal of Functional Biomaterials, ISSN 2079-4983, E-ISSN 2079-4983, Vol. 9, nr 2, artikel-id 26Artikel i tidskrift (Övrigt vetenskapligt)
  • 79.
    McLaughlin, Christopher
    et al.
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Fagerholm, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmiatrik. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US.
    Muzakare, Lea
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Lagali, Neil
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Forrester, John
    Department of Ophthalmology University of Aberdeen, Aberdeen, Scotland, United Kingdom.
    Kuffova, Lucia
    Department of Ophthalmology University of Aberdeen, Aberdeen, Scotland, United Kingdom.
    Rafat, Mehrdad
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Liu, Yuwen
    National Research Council Canada, Ottawa, Ontario, Canada.
    Shinozaki, Naoshi
    Tokyo Dental College-Ichikawa General Hospital Cornea Centre, Ichikawa, Chiba, Japan.
    Vascotto, Sandy
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Munger, Rejean
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Griffith, May
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Regeneration of Corneal Cells and Nerves in an Implanted Collagen Corneal Substitute2008Ingår i: Cornea, ISSN 0277-3740, E-ISSN 1536-4798, Vol. 27, nr 5, s. 580-589Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: Our objective was to evaluate promotion of tissue regeneration by extracellular matrix (ECM) mimics, by using corneal implantation as a model system.

    METHODS: Carbodiimide cross-linked porcine type I collagen was molded into appropriate corneal dimensions to serve as substitutes for natural corneal ECM. These were implanted into corneas of mini-pigs after removal of the host tissue, and tracked over 12 months, by clinical examination, slit-lamp biomicroscopy, in vivo confocal microscopy, topography, and esthesiometry. Histopathology and tensile strength testing were performed at the end of 12 months. Other samples were biotin labeled and implanted into mice to evaluate matrix remodeling.

    RESULTS: The implants promoted regeneration of corneal cells, nerves, and the tear film while retaining optical clarity. Mechanical testing data were consistent with stable, seamless host-graft integration in regenerated corneas, which were as robust as the untreated fellow corneas. Biotin conjugation is an effective method for tracking the implant within the host tissue.

    CONCLUSIONS: We show that a simple ECM mimetic can promote regeneration of corneal cells and nerves. Gradual turnover of matrix material as part of the natural remodeling process allowed for stable integration with host tissue and restoration of mechanical properties of the organ. The simplicity in fabrication and shown functionality shows potential for ECM   

  • 80.
    McLaughlin, Christopher R.
    et al.
    University of Ottawa Eye Inst., Ottawa, ON, Canada and Department of Cellular and Molecular Medicine, Univ. of Ottawa, Ottawa, ON, Canada.
    Tsai, Ray J-F
    Taipei Eye Center, Taipei Medical University, Taipei, Taiwan.
    Latorre, Malcolm A.
    University of Ottawa Eye Inst., Ottawa, ON, Canada and Department of Physics, Univ. of Ottawa, Ottawa ON, Canada.
    Griffith, May
    University of Ottawa Eye Inst., Ottawa, ON, Canada and Department of Cellular and Molecular Medicine, Univ. of Ottawa, Ottawa, ON, Canada.
    Bioengineered corneas for transplantation and in vitro toxicology2009Ingår i: Frontiers in Bioscience, ISSN 1093-9946, E-ISSN 1093-4715, Vol. 14, s. 3326-3337Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bioengineered corneas have been designed to replace partial or the full-thickness of defective corneas, as an alternative to using donor tissues. They range from prosthetic devices that solely address replacement of the corneas function, to tissue engineered hydrogels that permit regeneration of host tissues. In cases where corneal stem cells have been depleted by injury or disease, most frequently involving the superficial epithelium, tissue engineered lamellar implants reconstructed with stem cells have been transplanted. In situ methods using ultraviolet A (UVA) crosslinking have also been developed to strengthen weakened corneas. In addition to the clinical need, bioengineered corneas are also rapidly gaining importance in the area of in vitro toxicology, as alternatives to animal testing. More complex, fully innervated, physiologically active, three-dimensional organotypic models are also being tested.

  • 81.
    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.

  • 82.
    Merrett, K
    et al.
    Department of Chemical Engineering, University of Ottawa, Ottawa ON, Canada.
    Griffith, CM
    University of Ottawa Eye Institute, Ottawa ON, Canada.
    Deslandes, Y
    ICPET, National Research Council of Canada, Ottawa ON, Canada.
    Pleizier, G
    ICPET, National Research Council of Canada, Ottawa ON, Canada.
    Dube, MA
    Department of Chemical Engineering, University of Ottawa, Ottawa ON, Canada.
    Sheardown, H
    Departments of Chemical Engineering and Pathology and Molecular Medicine, McMaster University, Hamilton ON, Canada.
    Interactions of corneal cells with transforming growth factor beta 2-modified poly dimethyl siloxane surfaces2003Ingår i: Journal of Biomedical Materials Research, ISSN 0021-9304, E-ISSN 1097-4636, Vol. 67A, nr 3, s. 981-993Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The downgrowth of corneal epithelial cells at the interface of an artificial cornea and the host eye tissue poses a significant problem to be overcome in developing a successful implant. As a means of inhibiting the proliferation of corneal epithelial cells on the stromal surface of the implant, we examined the immobilization of transforming growth factor beta-2 (TGF-beta2) via a bifunctional poly ethylene glycol (PEG) spacer to poly dimethyl siloxane (PDMS) surfaces. Growth factor immobilization was confirmed by modification with I-125-labeled TGF-beta2. The modified surfaces were also characterized by advancing water contact angles, X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Although the amount of growth factor covalently bound to the surface was difficult to quantify apparently due to strong interactions between the growth factor and the PEG layer and high levels of adsorption, differences in the modified surfaces, suggestive of the presence of a significant amount of TGF-beta2, were found. In vitro interactions of the modified surfaces with human corneal epithelial and stromal cells were examined. Growth factor surface concentrations as well as culture in the absence and presence of serum and other adhesive proteins were examined. Corneal stromal and epithelial cells cultured on the TGF-beta2-modified surfaces consistently gave results opposite to those expected. Likely, the most notable and surprising result was the almost complete lack of adhesion of the stromal cells, with coverages averaging between 3 and 5%. In comparison, corneal epithelial cell growth appeared to be promoted by the presence of the immobilized growth factor, with cell coverages averaging 50 - 60% at 7 days of culture. A TGF-beta2 concentration effect was noted with both cell types in the absence of serum, with increases in the coverage at higher TGF-beta2 concentrations. The observed cell growth appeared to be the result of interactions between the cells and active growth factor, because the addition of antiTGF-beta2 to the culture medium reduced cell coverage to levels similar to those noted on control surfaces. Therefore, although TGF-beta2-modified surfaces may not be suitable as corneal epithelial cell inhibiting surfaces, interactions of surface immobilized growth factor and corneal cells are complex and should be further examined.

  • 83. Merrett, Kimberley
    et al.
    Fagerholm, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Oftalmologi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Ögonkliniken US/LiM.
    McLaughlin, Christopher R.
    Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada.
    Dravida, Subhadra
    Lagali, Neil
    University of Ottawa.
    Shinozaki, Naoshi
    Tokyo Dent Coll, Cornea Ctr & Eye Bank, Chiba, Japan.
    Watsky, Mitchell A.
    Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA.
    Munger, Rejean
    Kato, Yasuhiro
    Tokyo Dent Coll, Cornea Ctr & Eye Bank, Chiba, Japan.
    Li, Fengfu
    Marmo, Christopher J.
    CooperVision Inc, Pleasanton, CA USA.
    Griffith, May
    Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada.
    Tissue-engineered recombinant human collagen-based corneal substitutes for implantation: Performance of type I versus type III collagen2008Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 49, nr 9, s. 3887-3894Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. To compare the efficacies of recombinant human collagens types I and III as corneal substitutes for implantation. METHODS. Recombinant human collagen (13.7%) type I or III was thoroughly mixed with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. The final homogenous solution was either molded into sheets for in vitro studies or into implants with the appropriate corneal dimensions for transplantation into minipigs. Animals with implants were observed for up to 12 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, and fundus examination. Histopathologic examinations were also performed on corneas harvested after 12 months. RESULTS. Both cross-linked recombinant collagens had refractive indices of 1.35, with optical clarity similar to that in human corneas. Their chemical and mechanical properties were similar, although RHC-III implants showed superior optical clarity. Implants into pig corneas over 12 months show comparably stable integration, with regeneration of corneal cells, tear film, and nerves. Optical clarity was also maintained in both implants, as evidenced by fundus examination. CONCLUSIONS. Both RHC-I and -III implants can be safely and stably integrated into host corneas. The simple cross-linking methodology and recombinant source of materials makes them potentially safe and effective future corneal matrix substitutes.

  • 84.
    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.

  • 85.
    Merrett, Kimberly
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Kozak Ljunggren, Monika
    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.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Rafat, Mehrdad
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Collagen Type I: A Promising Scaffold Material for Tissue Engineering and Regenerative Medicine2012Ingår i: Type I collagen: biological functions, synthesis & medicinal applications / [ed] Maria Eduarda Henriques and Marcio Pinto, Nova Science Publishers, Inc., 2012, s. 1-43Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [en]

    It is now recognized that biological macromolecules such as components of the extracellular matrix (ECM) are important as instructive templates in Regenerative Medicine applications. They are now increasingly used in the development of a new generation of bio-mimetic materials that allow for restoration of function when the self-renewal capacity of a tissue or organ cannot overcome degeneration caused by disease, injury or age-related wear. For example, macromolecules derived from connective tissue have been isolated, chemically modified, and used in medical applications ranging from tissue repair and reconstruction to drug and cell delivery systems. Common ECM macromolecules of vertebrates include collagen, proteoglycans, elastin, and other cell-interactive proteins such as fibronectin and laminin. Of these, type I collagen is the most abundant ECM macromolecule and is the primary scaffolding material that maintains the 3-dimensional structure of tissues and organs within the body. It also provides the micro-environmental milieu for cellular attachment, migration, and proliferation.

    Animal-derived collagen is frequently used in tissue engineering applications due to its biocompatibility, but there are significant concerns about the immunogenicity of xenogeneic material as well as the possibility of pathogen transmission. Most recently, synthetic collagens and recombinant human collagens have been produced for medical application. Regardless of the source, however, macromolecules require processing and chemical treatment in order to improve their stability both in vitro and in vivo. This is most commonly achieved by cross-linking using a variety of agents. Cross-linking also allows for the development of “tailor-made” collagen-based biomaterials that possess specific properties for tissue engineering. Chemical cross-linkers such as glutaraldehyde and epoxy compounds are frequently used but their cytotoxicities have limited their clinical application. This has led to the use of zero-length cross-linkers such as carbodiimides and naturally derived agents such as genipin. Enzymatic cross-linking is becoming an attractive method to induce in situ biomaterial formation due to the mildness of the reaction. Naturally occurring enzymes such as transglutaminase are now commonly used. Photosensitizers used in combination with ultra-violet light irradiation can be used as exogenous cross-linkers. For example, riboflavin in combination with ultra-violet light is used clinically to augment the properties of collagen-based tissues such as the sclera and the cornea.

    Collagen type I is a good candidate for tissue engineering and in vivo delivery systems for cells, proteins, and drugs. Important to its versatile and functional nature are its chemotactic properties, which promote cellular proliferation and differentiation, richness in cross-linking sites, and biodegradability. Collagen based delivery matrices have been reported to improve the results of cell delivery by improving cell viability.

  • 86.
    Moelzer, Christine
    et al.
    Univ Aberdeen, Scotland.
    Shankar, Sucharita P.
    Univ Aberdeen, Scotland; UCB Pharma, England.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Univ Montreal, Canada.
    Mirazul Islam, Mohammad Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Harvard Med Sch, MA 02115 USA; Harvard Med Sch, MA 02115 USA.
    Forrester, John V
    Univ Aberdeen, Scotland.
    Kuffova, Lucia
    Univ Aberdeen, Scotland.
    Activation of dendritic cells by crosslinked collagen hydrogels (artificial corneas) varies with their composition2019Ingår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Activated T cells are known to promote fibrosis, a major complication limiting the range of polymeric hydrogels as artificial corneal implants. As T cells are activated by dendritic cells (DC), minimally activating hydrogels would be optimal. In this study, we evaluated the ability of a series of engineered (manufactured/fabricated) and natural collagen matrices to either activate DC or conversely induce DC apoptosis in vitro. Bone marrow DC were cultured on a series of singly and doubly crosslinked hydrogels (made from recombinant human collagen III [RHCIII] or collagen mimetic peptide [CMP]) or on natural collagen-containing matrices, Matrigel(TM) and de-cellularised mouse corneal stroma. DC surface expression of major histocompatibility complex Class II and CD86 as well as apoptosis markers were examined. Natural matrices induced low levels of DC activation and maintained a "tolerogenic" phenotype. The same applied to singly crosslinked CMP-PEG gels. RHCIII gels singly crosslinked using either N-(3-dimethylaminopropyl)-N -ethylcarbodiimide with the coinitiator N-hydroxy succinimide (EDC-NHS) or N-cyclohexyl-N-(2-morpholinoethyl)carbodiimide metho-p-toulenesulfonate with NHS (CMC-NHS) induced varying levels of DC activation. In contrast, however, RHCIII hydrogels incorporating an additional polymeric network of 2-methacryloyloxyethyl phosphorylcholine did not activate DC but instead induced DC apoptosis, a phenomenon observed in natural matrices. This correlated with increased DC expression of leukocyte-associated immunoglobulin-like receptor-1. Despite low immunogenic potential, viable tolerogenic DC migrated into and through both natural and manufactured RHCIII gels. These data show that the immunogenic potential of RHCIII gels varies with the nature and composition of the gel. Preclinical evaluation of hydrogel immunogenic/fibrogenic potential is recommended.

  • 87.
    Molzer, Christine
    et al.
    Univ Aberdeen, Scotland.
    Shankar, Sucharita P.
    Univ Aberdeen, Scotland; UCB Pharma, England.
    Masalski, Vlad
    Univ Aberdeen, Scotland.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Univ Montreal, Canada; Maisonneuve Rosemont Hosp Res Ctr, Canada.
    Kuffova, Lucia
    Univ Aberdeen, Scotland.
    Forrester, John V
    Univ Aberdeen, Scotland.
    TGF-beta 1-activated type 2 dendritic cells promote wound healing and induce fibroblasts to express tenascin c following corneal full-thickness hydrogel transplantation2019Ingår i: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We showed previously that 1-ethyl-3-(3-dimethylamino-propyl)-carbodiimide hydrochloride (EDC) cross-linked recombinant human collagen III hydrogels promoted stable regeneration of the human cornea (continued nerve and stromal cell repopulation) for over 4 years. However, as EDC cross linking kinetics were difficult to control, we additionally tested a sterically bulky carbodiimide. Here, we compared the effects of two carbodiimide cross linkers-bulky, aromatic N-cyclohexyl-N0-(2-morpholinoethyl)-carbodiimide (CMC), and nonbulky EDC-in a mouse corneal graft model. Murine corneas undergoing full-thickness implantation with these gels became opaque due to dense retro-corneal membranes (RCM). Corneal epithelial cytokeratin 12 and alpha smooth muscle actin indicative of functional tissue regeneration and wound contraction were observed in RCM surrounding both hydrogel types. However, quantitatively different levels of infiltrating CD11c(+) dendritic cells (DC) were found, suggesting a hydrogel-specific innate immune response. More DC infiltrated the stroma surrounding EDC-N-hydroxysuccinimide (NHS) hydrogels concurrently with higher fibrosis-associated tenascin c expression. The opposite was true for CMC-NHS gels that had previously been shown to be more tolerising to DC. In vitro studies showed that DC cultured with transforming growth factor beta 1 (TGF-beta 1) induced fibroblasts to secrete more tenascin c than those cultured with lipopolysaccharide and this effect was blocked by TGF-beta 1 neutralisation. Furthermore, tenascin c staining was found in 40- to 50 mu m long membrane nanotubes formed in fibroblast/DC cocultures. We suggest that TGF-beta 1 alternatively activated (tolerising) DC regulate fibroblast-mediated tenascin c secretion, possibly via local production of TGF-beta 1 in early wound contraction, and that this is indirectly modulated by different hydrogel chemistries.

  • 88.
    Mondal, Debasish
    et al.
    Singapore Eye Research Institute, Singapore.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Venkatraman, Subbu S.
    Nanyang Technology University, Singapore.
    Polycaprolactone-based biomaterials for tissue engineering and drug delivery: Current scenario and challenges2016Ingår i: International Journal of Polymeric Materials, ISSN 0091-4037, E-ISSN 1563-535X, Vol. 65, nr 5, s. 255-265Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recently, poly (epsilon-caprolactone) (PCL) has gained a lot of attention, and shown great potential in biomedical applications. Among synthetic polymers, PCL is one of the easiest to process and manipulate into a large range of shapes and sizes due to its low melting temperature and its superior viscoelastic properties. In this review article the authors focus mainly on the properties of PCL-based biomaterials relevant to drug delivery and tissue engineering applications. The authors provide an insight into the recent developments and challenges of PCL-based biomaterials as a critical component of new therapeutic strategies for many diseases.

  • 89.
    Newman, K.D.
    et al.
    University Ottawa Eye Institute, Ottawa Hospital, General Campus, Ottawa, Ontario, Canada.
    McLaughlin, C.R.
    University Ottawa Eye Institute, Ottawa Hospital, General Campus, Ottawa, Ontario, Canada.
    Carlsson, D.
    National Research Council, Ottawa, Ontario, Canada.
    Li, F.
    University Ottawa Eye Institute, Ottawa Hospital, General Campus, Ottawa, Ontario, Canada.
    Liu, Y.
    National Research Council, Ottawa, Ontario, Canada.
    Griffith, M.
    University Ottawa Eye Institute, Ottawa Hospital, General Campus, Ottawa, Ontario, Canada.
    Bioactive hydrogel-filament scaffolds for nerve repair and regeneration2006Ingår i: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 29, nr 11, s. 1082-1091Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The design of novel biomaterials is crucial for the advancement of tissue engineering in nerve regeneration. In this study we developed and evaluated novel biosynthetic scaffolds comprising collagen crosslinked with a terpolymer of poly(N-isopropylacrylamide) (PNiPAAm) as conduits for nerve growth. These collagen-terpolymer (collagen-TERP) scaffolds grafted with the laminin pentapeptide YIGSR were previously used as corneal substitutes in pigs and demonstrated enhanced nerve regeneration compared to allografts. The purpose of this project was to enhance neuronal growth on the collagen-TERP scaffolds through the incorporation of supporting fibers. Neuronal growth on these matrices was assessed in vitro using isolated dorsal root ganglia as a nerve source. Statistical significance was assessed using a one-way ANOVA. The incorporation of fibers into the collagen-TERP scaffolds produced a significant increase in neurite extension (p less than 0.05). The growth habit of the nerves varied with the type of fiber and included directional growth of the neurites along the surface of certain fiber types. Furthermore, the presence of fibers in the collagen-TERP scaffolds appeared to influence neurite morphology and function; neurites grown on fibers-incorporated collagen-TERP scaffolds expressed higher levels of Na channels compared to the scaffolds without fiber. Overall, our results suggest that incorporation of supporting fibers enhanced neurite outgrowth and that surface properties of the scaffold play an important role in promoting and guiding nerve regeneration. More importantly, this study demonstrates the potential value of tissue engineered collagen-TERP hybrid scaffolds as conduits in peripheral nerve repair.

  • 90.
    Nokhbeh, M. Reza
    et al.
    Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Faculty of Medicine, Ottawa, ON, Canada.
    Hazra, Samir
    Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Faculty of Medicine, Ottawa, ON, Canada.
    Alexander, David A.
    Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Faculty of Medicine, Ottawa, ON, Canada.
    Khan, Ahmar
    Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Faculty of Medicine, Ottawa, ON, Canada.
    McAllister, Morgan
    Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Faculty of Medicine, Ottawa, ON, Canada.
    Suuronen, Erik J.
    Department of Cellular and Molecular Medicine, University of Ottawa, Faculty of Medicine, Ottawa, ON, Canada and University of Ottawa Eye Institute, Ottawa, ON, Canada.
    Griffith, May
    Department of Cellular and Molecular Medicine, University of Ottawa, Faculty of Medicine, Ottawa, ON, Canada and University of Ottawa Eye Institute, Ottawa, ON, Canada.
    Dimock, Kenneth
    Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Faculty of Medicine, Ottawa, ON, Canada.
    Enterovirus 70 binds to different glycoconjugates containing alpha 2,3-linked sialic acid on different cell lines2005Ingår i: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 79, nr 11, s. 7087-7094Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Enterovirus 70 (EV70), the causative agent of acute hemorrhagic conjunctivitis, exhibits a restricted tropism for conjunctival and corneal cells in vivo but infects a wide spectrum of mammalian cells in culture. Previously, we demonstrated that human CD55 is a receptor for EV70 on HeLa cells but that EV70 also binds to sialic acid-containing receptors on a variety of other human cell lines. Virus recognition of sialic acid attached to underlying glycans by a particular glycosidic linkage may contribute to host range, tissue tropism, and pathogenesis. Therefore, we tested the possibility that EV70 binds to andalpha; 2,3-linked sialic acid, like other viruses associated with ocular infections. Through the use of linkage-specific sialidases, sialyltransferases, and lectins, we show that EV70 recognizes andalpha; 2,3-linked sialic acid on human corneal epithelial cells and on U-937 cells. Virus attachment to both cell lines is CD55 independent and sensitive to benzyl N-acetyl-andalpha;-D-galactosaminide, an inhibitor of O-linked glycosylation. Virus binding to corneal cells, but not U-937 cells, is inhibited by proteinase K, but not by phosphatidylinositol-specific phospholipase C treatment. These results are consistent with the idea that a major EV70 receptor on corneal epithelial cells is an O-glycosylated, non-glycosyl phosphatidylinositol-anchored membrane glycoprotein containing andalpha; 2,3-linked sialic acid, while sialylated receptors on U-937 cells are not proteinaceous.

  • 91.
    Ong, Jeb A.
    et al.
    Maisonneuve Rosemt Hospital, Canada; University of Montreal, Canada.
    Auvinet, Edouard
    University of Montreal, Canada.
    Forget, Karolyn J.
    Maisonneuve Rosemt Hospital, Canada.
    Lagali, Neil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Ögonkliniken US/LiM.
    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.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Maisonneuve Rosemt Hospital, Canada.
    Meunier, Jean
    University of Montreal, Canada; University of Montreal, Canada.
    Brunette, Isabelle
    Maisonneuve Rosemt Hospital, Canada; University of Montreal, Canada.
    3D Corneal Shape After Implantation of a Biosynthetic Corneal Stromal Substitute2016Ingår i: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 57, nr 6, s. 2355-2365Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE. The current and projected shortage of transplantable human donor corneas has prompted the development of long-term alternatives to human donor tissue for corneal replacement. The biosynthetic stromal substitutes (BSS) characterized herein represent a potentially safe alternative to donor organ transplantation for anterior corneal stromal diseases. The goal of this phase 1 safety study was to characterize the three-dimensional (3D) corneal shape of the first 10 human patients implanted with a BSS and assess its stability over time. METHODS. Ten patients underwent anterior lamellar keratoplasty using a biosynthetic corneal stromal implant for either advanced keratoconus or central corneal scarring. Surgeries were performed at Linkoping University Hospital, between October and November 2007. Serial corneal topographies were performed on all eyes up to a 4-year follow-up when possible. Three-dimensional shape average maps were constructed for the 10 BSS corneas and for 10 healthy controls. Average 3D shape corneal elevation maps, difference maps, and statistics maps were generated. RESULTS. The biosynthetic stromal substitutes implants remained stably integrated into the host corneas over the 4-year follow-up period, without signs of wound dehiscence or implant extrusion. The biosynthetic stromal substitutes corneas showed steeper surface curvatures and were more irregular than the healthy controls. CONCLUSIONS. Corneal astigmatism and surface steepness were observed 4 years after BSS implantation, while the implants remained stably integrated in the host corneas. Future studies will indicate if biomaterials technology will allow for the optimization of postoperative surface irregularity after anterior stromal replacement, a new window of opportunity that is not available with traditional corneal transplantation techniques.

  • 92.
    Orban, Jenny
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska högskolan.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Turner, Anthony
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska högskolan.
    Viter, R
    Linköpings universitet, Hälsouniversitetet.
    Bechelany, M
    Linköpings universitet, Hälsouniversitetet.
    Mak, Martin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska högskolan.
    Surface nanoengineered contact lens as a wearable point-of-care diagnostics platform2014Ingår i: 24th Anniversary World Congress on Biosensors – Biosensors 2014, Elsevier, 2014Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Detection of biomarkers is essential for disease prevention, diagnosis, and prognosis of early stage treatment. Ocular fluid is an extracellular fluid excreted from the tear gland. Several important markers from ocular fluid have been identified having significant clinical diagnostic value for various diseases. The contact lens is disposable, relatively cheap and serves as a platform to obtain direct intimate contact with ocular fluid and is therefore an attractive and a promising platform for point-of-care diagnostic tests. Here, we present an innovative concept of a wearable contact lens biosensor with nanoengineered biorecognition architecture based on a Layer-by-Layer (LbL) technique on the contact lens surface. This technique enables us to deposit multiple layers of biomolecules to create biorecognition layer under a mild aqueous physiological temperature and pH conditions. The fabrication of the biorecognition layer is simply through physical adsorption and has no restrictions with respect to the substrate size and topology (i.e. contact lens). The thickness of the resulting biorecognition layer is only hundreds of nanometers, and hence has minimal influence on the overall thickness of the contact lens, thus preserving the optical properties of the contact lens for vision correction. We have demonstrated that eye inflammation biomarkers such as interleukin (IL) can be captured in vitro with the contact lens, thus facilitating colorimetric affinity bioassays to measure the amount of interleukin. An in vitro ocular model composed of hydrogel-based artificial cornea and microfluidics was developed to study the performance of the contact lens biosensing platform. The contact  platform was able to detect IL-1α down to the physiological concentration, which is in the range of pg mL-1. There is a recent trend away from handheld devices towards wearable systems, illustrated by popular technology such as “Google glasses” and the “i-Watch”. We believe that the concept of wearable diagnostics holds significant promise as the next generation point-of-care diagnostic platform and that this contact lens-based approach is a convenient platform for a number of important applications.

  • 93.
    Orban, Jenny
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska högskolan.
    Turner, Anthony
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska högskolan.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Mak, Martin
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biosensorer och bioelektronik. Linköpings universitet, Tekniska högskolan.
    Wearable contact lens biosensors with nanoengineered biorecognition layer2013Ingår i: BioSensing Technologies, 2013 / [ed] Richard Luxton, Amsterdam: Elsevier, 2013Konferensbidrag (Övrigt vetenskapligt)
  • 94.
    Paaske Utheim, Tor
    et al.
    Oslo University Hospital, Norway; University of Oslo, Norway; Vestre Viken HF Trust, Norway; Buskerud and Vestfold University of Coll, Norway.
    Islam, Rakibul
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Fostad, Ida G.
    University of Oslo, Norway.
    Eidet, Jon R.
    Oslo University Hospital, Norway.
    Sehic, Amer
    University of Oslo, Norway.
    Olstad, Ole K.
    Oslo University Hospital, Norway.
    Dartt, Darlene A.
    Harvard University, MA USA.
    Messelt, Edward B.
    University of Oslo, Norway.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Pasovic, Lara
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Storage Temperature Alters the Expression of Differentiation-Related Genes in Cultured Oral Keratinocytes2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 3, s. e0152526-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose Storage of cultured human oral keratinocytes (HOK) allows for transportation of cultured transplants to eye clinics worldwide. In a previous study, one-week storage of cultured HOK was found to be superior with regard to viability and morphology at 12 degrees C compared to 4 degrees C and 37 degrees C. To understand more of how storage temperature affects cell phenotype, gene expression of HOK before and after storage at 4 degrees C, 12 degrees C, and 37 degrees C was assessed. Materials and Methods Cultured HOK were stored in HEPES-and sodium bicarbonate-buffered Minimum Essential Medium at 4 degrees C, 12 degrees C, and 37 degrees C for one week. Total RNA was isolated and the gene expression profile was determined using DNA microarrays and analyzed with Partek Genomics Suite software and Ingenuity Pathway Analysis. Differentially expressed genes (fold change &gt; 1.5 and P &lt; 0.05) were identified by one-way ANOVA. Key genes were validated using qPCR. Results Gene expression of cultures stored at 4 degrees C and 12 degrees C clustered close to the unstored control cultures. Cultures stored at 37 degrees C displayed substantial change in gene expression compared to the other groups. In comparison with 12 degrees C, 2,981 genes were differentially expressed at 37 degrees C. In contrast, only 67 genes were differentially expressed between the unstored control and the cells stored at 12 degrees C. The 12 degrees C and 37 degrees C culture groups differed most significantly with regard to the expression of differentiation markers. The Hedgehog signaling pathway was significantly downregulated at 37 degrees C compared to 12 degrees C. Conclusion HOK cultures stored at 37 degrees C showed considerably larger changes in gene expression compared to unstored cells than cultured HOK stored at 4 degrees C and 12 degrees C. The changes observed at 37 degrees C consisted of differentiation of the cells towards a squamous epithelium-specific phenotype. Storing cultured ocular surface transplants at 37 degrees C is therefore not recommended. This is particularly interesting as 37 degrees C is the standard incubation temperature used for cell culture.

  • 95.
    Polisetti, Naresh
    et al.
    University of Erlangen-Nürnberg, Erlangen, Germany.
    Islam, Mohammad Mirazul
    Swedish Medical Nanoscience Center, Karolinska Institute, Stockholm, Sweden.
    Griffith, May
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi.
    The artificial cornea2013Ingår i: Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029, Vol. 1014, s. 45-52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human corneal transplantation to date suffers from the shortage of good-quality donor tissue, and in some conditions, allografting is contraindicated. A range of artificial replacements to donor allograft corneas have been developed. These range from keratoprostheses (KPro) that replace basic corneal functions of light transmission and protection to regenerative medicine strategies for regenerating one or more layers of the human cornea. This chapter reviews the advances made in developing artificial corneas or more accurately, artificial alternatives to donor allograft corneas for ocular application.

  • 96.
    Polisetti, Naresh
    et al.
    University of Erlangen-Nürnberg, Erlangen, Germany.
    McLaughlin, Christopher R.
    Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada.
    Vemuganti, Geeta K.
    School of Medical Sciences, University of Hyderabad, Andhra Pradesh, India.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Biomaterials-Enabled Regenerative Medicine in Corneal Applications2013Ingår i: Regenerative Medicine: From Protocol to Patient / [ed] Steinhoff, Gustav, Springer Netherlands, 2013, 2, s. 557-580Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [en]

    This book details the latest scientific and clinical knowledge in regenerative medicine. Coverage includes biology of tissue regeneration, stem cell science and technology, tissue engineering, biomaterials and nanotechnology, and regulation and ethics.

  • 97.
    Pupkaite, Justina
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. University of Ottawa, Canada.
    Ahumada, Manuel
    University of Ottawa, Canada.
    Mclaughlin, Sarah
    University of Ottawa, Canada.
    Temkit, Moho
    University of Ottawa, Canada.
    Alaziz, Sura
    University of Ottawa, Canada.
    Seymour, Richard
    University of Ottawa, Canada.
    Ruel, Marc
    University of Ottawa, Canada.
    Kochevar, Irene
    Harvard Medical Sch, MA USA.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Suuronen, Erik J.
    University of Ottawa, Canada.
    Alarcon, Emilio I.
    University of Ottawa, Canada.
    Collagen-Based Photoactive Agent for Tissue Bonding2017Ingår i: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 9, nr 11, s. 9265-9270Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Using a combination of methacrylated, collagen and the photosensitizer rose Bengal, a new light-activated biomimetic material for tissue sutureless bonding was developed. This formulation was cross-linked using green light. In vivo tests in mice demonstrate the suitability of the material for sutureless wound closure.

  • 98.
    Rafat, Mehrdad
    et al.
    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.
    Merret, K,
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. 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.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Collagen-based bioengineered corneas: a material development update2011Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Purpose

    Our overall objective is to develop novel biomimetic materials that support the regeneration of diseased or damaged corneal tissue. This presentation will provide an update on such materials developed in our group.

    Methods

    We have developed a range of collagen-based materials as mimics of the cell-free corneal stromal extracellular matrix. Promising material formulations were tested pre-clinically for their physical properties (e.g. mechanical, optical, water uptake, etc.) and physiological properties (e.g. interactions with corneal cells, biodegradation, in vivo implantation in animals etc.). One of the early formulations was clinically tested in the corneas of 10 patients, results of which will be discussed.

    Results

    More recently, our team of Canadian and Swedish researchers reported the successful implantation of cell-free, bioengineered corneas into patients with keratoconus and central scarring in a Phase 1 clinical trial. These implants acted as stable scaffolds that promoted functional regeneration of corneal cells and nerves. At 24 months post-operative, six of the ten patients could see four times further than before the operation. With the help of rigid contact lenses – the results in all ten patients were similar to what the traditional corneal transplant with human donor tissue would be, with one patient achieving 20/20 vision and two others with 20/25 vision.

    Conclusions

    Despite the promising clinical results, more robust and elastic materials are required to withstand the adverse host conditions faced for high risk transplantation in severely damaged or diseased corneas as well as for full-thickness corneal implants. Examples of next generation biomaterials that have been implanted into animal models as partial and full-thickness grafts that allow regeneration of nerve sub-types and show resistance to neovascularization will be shown.

  • 99.
    Rafat, Mehrdad
    et al.
    Department of Chemical Engineering, University of Ottawa and 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.
    Hakim, Malik
    Department of Chemical Engineering, University of Ottawa and University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Muzakare, Lea
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Li, Frank
    University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
    Khulbe, K.C.
    Department of Chemical Engineering, University of Ottawa, Ottawa, Ontario, Canada.
    Matsuura, Takeshi
    Department of Chemical Engineering, University of Ottawa, Ottawa, Ontario, Canada.
    Plasma surface modification and characterization of collagen-based artificial cornea for enhanced epithelialization2007Ingår i: Journal of Applied Polymer Science, ISSN 0021-8995, E-ISSN 1097-4628, Vol. 106, nr 3, s. 2056-2064Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Argon plasma treatment enhanced the attachment of epithelial cells to a collagen-based artificial cornea crosslinked using glutaraldehyde (GA) and glutaraldehyde-polyethylene oxide dialdehyde (GA-PEODA) systems. The epithelialization of untreated and treated surfaces was evaluated by the seeding and growth of human corneal epithelial cells. Characterization of polymer surface properties such as surface hydrophilicity and roughness was also made by contact angle measurement and atomic force microscopy, respectively. Contact angle analysis revealed that the surface hydrophilicity significantly increased after the treatment. In addition, AFM characterization showed an increase in surface roughness through argon plasma treatment. Based on the biological and surface analysis, argon plasma treatment displays promising potential for biocompatibility enhancement of collagen-based artificial corneas. It was also found that the cell attachment to artificial cornea surfaces was influenced by the combined effects of surface chemistry (i.e., surface energy), polymer surface morphology (i.e., surface roughness), and polar interactions between functional groups at the polymer surface and cell membrane proteins.

  • 100.
    Rafat, Mehrdad
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Filosofiska fakulteten.
    Hackett, Joanne
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. 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.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Artificial Cornea2011Ingår i: Ocular Periphery and Disorders / [ed] Darlene A. Dartt, Peter Bex, Patricia D'Amore, Reza Dana, Linda Mcloon, Jerry Niederkorn, Elsevier, 2011, s. 311-317Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [en]

    This selection of articles from the Encyclopedia of the Eye is the first single-volume overview presenting articles on the function, biology, physiology, and pathology of the structures of the ocular periphery, as well as the related disorders and their treatment. The peripheral structures are implicated in a number of important diseases, including optic neuritis, thyroid eye disease, and strabismus. The volume offers a basic science background of these topics rather than a strictly clinical focus.

    *The first single volume to integrate comparative studies into a comprehensive resource on the neuroscience of the ocular periphery

    *Chapters are carefully selected from the Encyclopedia of the Eye by the world's leading vision researchers

    *The best researchers in the field provide their conclusions in the context of the latest experimental results

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