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      LiQD Cornea: Pro-regeneration collagen mimetics as patches and alternatives to corneal transplantation

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          Abstract

          LiQD Cornea is a liquid in situ gelling, pro-regeneration hydrogel for treating corneal blindness and repairing perforations.

          Abstract

          Transplantation with donor corneas is the mainstay for treating corneal blindness, but a severe worldwide shortage necessitates the development of other treatment options. Corneal perforation from infection or inflammation is sealed with cyanoacrylate glue. However, the resulting cytotoxicity requires transplantation. LiQD Cornea is an alternative to conventional corneal transplantation and sealants. It is a cell-free, liquid hydrogel matrix for corneal regeneration, comprising short collagen-like peptides conjugated with polyethylene glycol and mixed with fibrinogen to promote adhesion within tissue defects. Gelation occurs spontaneously at body temperature within 5 min. Light exposure is not required—particularly advantageous because patients with corneal inflammation are typically photophobic. The self-assembling, fully defined, synthetic collagen analog is much less costly than human recombinant collagen and reduces the risk of immune rejection associated with xenogeneic materials. In situ gelation potentially allows for clinical application in outpatient clinics instead of operating theaters, maximizing practicality, and minimizing health care costs.

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          Most cited references26

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          Bone Marrow-Derived Macrophages (BMM): Isolation and Applications

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            An SV40-immortalized human corneal epithelial cell line and its characterization.

            The authors attempted to immortalize human corneal epithelial cells; it is difficult to propagate primary human corneal epithelial cells because of scarcity of available tissue. However, cell immortalization by virus is always accompanied by shedding of free virus. The current study was performed to establish a cell line that produces no free viral particle. Primary cultured human corneal epithelial cells were infected with a recombinant sv40-adenovirus vector and were cloned three times to obtain a continuously growing cell line. Morphologic, cytologic, and biochemical characteristics of this cell line were analyzed. This cell line continued to grow for more than 400 generations, exhibiting a cobblestone-like appearance similar to normal corneal epithelial cells in culture. Transmission electron microscopy showed the evidence for the characteristic features of epithelial cells, including desmosome formation and development of microvilli. It expressed cornea-specific, 64-kD cytokeratin in addition to five major insoluble proteins. By enzymatic analysis using NADP as a coenzyme and a gas chromatograph mass spectrometer, this cell line was found to possess 8.71 IU/mg protein of aldehydedehydrogenase activity. When this cell line was grown at air-liquid interface on collagen type I gel, it differentiated in a multilayered fashion. The authors have established an SV40-immortalized human corneal epithelial cell line with properties similar to normal corneal epithelial cells.
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              Management of corneal perforation.

              Corneal perforation may be associated with prolapse of ocular tissue and requires prompt diagnosis and treatment. Although infectious keratitis is an important cause, corneal xerosis and collagen vascular diseases should be considered in the differential diagnosis, especially in cases that do not respond to conventional medical therapy. Although medical therapy is a useful adjunct, a surgical approach is required for most corneal perforations. Depending on the size and location of the corneal perforation, treatment options include gluing, amniotic membrane transplantation, and corneal transplantation. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Sci Adv
                Sci Adv
                SciAdv
                advances
                Science Advances
                American Association for the Advancement of Science
                2375-2548
                June 2020
                17 June 2020
                : 6
                : 25
                : eaba2187
                Affiliations
                [1 ]Centre de Recherche Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada.
                [2 ]Department of Ophthalmology and Institute of Biomedical Engineering, Université de Montréal, Montréal, QC, Canada.
                [3 ]Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, ON, Canada.
                [4 ]Department of Ophthalmology, Visual Optics and Visual Rehabilitation, University of Antwerp, Antwerp, Belgium.
                [5 ]Centre for Vision Research, The Westmead Institute for Medical Research, and Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
                [6 ]Institute for Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
                [7 ]School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK.
                [8 ]Laboratory of Cell Biology and Histology, University of Antwerp, Antwerp, Belgium.
                [9 ]FibroGen Inc., San Francisco, CA, USA.
                [10 ]NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK.
                Author notes
                [*]

                These authors contributed equally to this work.

                []Corresponding author. Email: may.griffith@ 123456umontreal.ca (M. Griffith); bruce.allan@ 123456ucl.ac.uk (B.D.A.)
                Author information
                http://orcid.org/0000-0002-1181-9420
                http://orcid.org/0000-0003-3534-050X
                http://orcid.org/0000-0003-1568-556X
                http://orcid.org/0000-0002-6688-0480
                http://orcid.org/0000-0002-6116-1524
                http://orcid.org/0000-0003-4253-998X
                http://orcid.org/0000-0001-8465-1764
                http://orcid.org/0000-0002-8503-4482
                http://orcid.org/0000-0003-1222-6720
                Article
                aba2187
                10.1126/sciadv.aba2187
                7299624
                32917640
                25508165-a628-401b-bd69-a966147bbd1d
                Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                History
                : 14 November 2019
                : 08 May 2020
                Funding
                Funded by: doi http://dx.doi.org/10.13039/100014461, NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research;
                Award ID: BRC-1215-20002
                Funded by: Euronanomedicine II - Swedish Research Council;
                Award ID: IKE-2014-00597
                Funded by: Euronanomedicine III-Fonds de la recherche en sante du Quebec;
                Award ID: 278653
                Funded by: Westmead Charitable Trust Early Career Research Fellowship;
                Award ID: CC368629-8245
                Funded by: Vision Health Research Network-FRQS;
                Award ID: RNI-2017-03
                Categories
                Research Article
                Research Articles
                SciAdv r-articles
                Health and Medicine
                Custom metadata
                Penchie Limbo

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