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      Gelatin-Based Materials in Ocular Tissue Engineering

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          Abstract

          Gelatin has been used for many years in pharmaceutical formulation, cell culture and tissue engineering on account of its excellent biocompatibility, ease of processing and availability at low cost. Over the last decade gelatin has been extensively evaluated for numerous ocular applications serving as cell-sheet carriers, bio-adhesives and bio-artificial grafts. These different applications naturally have diverse physical, chemical and biological requirements and this has prompted research into the modification of gelatin and its derivatives. The crosslinking of gelatin alone or in combination with natural or synthetic biopolymers has produced a variety of scaffolds that could be suitable for ocular applications. This review focuses on methods to crosslink gelatin-based materials and how the resulting materials have been applied in ocular tissue engineering. Critical discussion of recent innovations in tissue engineering and regenerative medicine will highlight future opportunities for gelatin-based materials in ophthalmology.

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          The retinal pigment epithelium in health and disease.

          J R Sparrow, D. Hicks, C Hamel (2010)
          Retinal pigment epithelial cells (RPE) constitute a simple layer of cuboidal cells that are strategically situated behind the photoreceptor (PR) cells. The inconspicuousness of this monolayer contrasts sharply with its importance [1]. The relationship between the RPE and PR cells is crucial to sight; this is evident from basic and clinical studies demonstrating that primary dysfunctioning of the RPE can result in visual cell death and blindness. RPE cells carry out many functions including the conversion and storage of retinoid, the phagocytosis of shed PR outer segment membrane, the absorption of scattered light, ion and fluid transport and RPE-PR apposition. The magnitude of the demands imposed on this single layer of cells in order to execute these tasks, will become apparent to the reader of this review as will the number of clinical disorders that take origin from these cells.
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            Microfabrication of complex porous tissue engineering scaffolds using 3D projection stereolithography.

            Robert Gauvin, Ying-Chieh Chen, Jin Lee … (2012)
            The success of tissue engineering will rely on the ability to generate complex, cell seeded three-dimensional (3D) structures. Therefore, methods that can be used to precisely engineer the architecture and topography of scaffolding materials will represent a critical aspect of functional tissue engineering. Previous approaches for 3D scaffold fabrication based on top-down and process driven methods are often not adequate to produce complex structures due to the lack of control on scaffold architecture, porosity, and cellular interactions. The proposed projection stereolithography (PSL) platform can be used to design intricate 3D tissue scaffolds that can be engineered to mimic the microarchitecture of tissues, based on computer aided design (CAD). The PSL system was developed, programmed and optimized to fabricate 3D scaffolds using gelatin methacrylate (GelMA). Variation of the structure and prepolymer concentration enabled tailoring the mechanical properties of the scaffolds. A dynamic cell seeding method was utilized to improve the coverage of the scaffold throughout its thickness. The results demonstrated that the interconnectivity of pores allowed for uniform human umbilical vein endothelial cells (HUVECs) distribution and proliferation in the scaffolds, leading to high cell density and confluency at the end of the culture period. Moreover, immunohistochemistry results showed that cells seeded on the scaffold maintained their endothelial phenotype, demonstrating the biological functionality of the microfabricated GelMA scaffolds. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              Relationship between triple-helix content and mechanical properties of gelatin films.

              K Rubini, S Panzavolta, Mohammad Babaee Bigi (2004)
              This paper reports a study on the influence of the renaturation level of gelatin on the mechanical and swelling properties of gelatin films. Films at different renaturation level were obtained from gelatin samples with different Bloom index. It was verified that the triple-helix content, calculated from the values of the enthalpy of denaturation associated to the endothermal transition at about 41 degrees C of gelatin, increases with the Bloom index. The d.s.c. data are further supported by the results of the X-ray diffraction investigation carried out on the same samples. The increase of triple-helix content provokes a significant reduction in the degree of swelling, and a remarkable improvement of the mechanical properties of the films. The elastic Young's modulus, E, increases linearly with the renaturation level, from 3.6 to 12.0 MPa. Crosslinking with GTA 1% remarkably reduces the degree of swelling of all the samples, and induces a further increase of the Young's modulus, which reaches values up to 27 MPa.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Materials (Basel)
                Journal ID (iso-abbrev): Materials (Basel)
                Journal ID (publisher-id): Materials
                Title: Materials
                Publisher: MDPI
                ISSN (Electronic): 1996-1944
                Publication date Collection: April 2014
                Publication date (Electronic): 17 April 2014
                Volume: 7
                Issue: 4
                Pages: 3106-3135
                Affiliations
                [1 ]School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK; E-Mails: paxjr@ 123456nottingham.ac.uk (J.B.R.); lisa.white@ 123456nottingham.ac.uk (L.J.W.)
                [2 ]Department of Drug Chemistry and Technologies, “Sapienza” University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy; E-Mail: settimio.pacelli@ 123456uniroma1.it
                [3 ]Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent ST4 7QB, UK; E-Mail: a.j.el.haj@ 123456keele.ac.uk
                [4 ]Academic Ophthalmology, Division of Clinical Neuroscience, University of Nottingham, Nottingham NG7 2RD, UK; E-Mails: harminder.dua@ 123456nottingham.ac.uk (H.S.D.); andrew.hopkinson@ 123456nottingham.ac.uk (A.H.)
                Author notes
                [†]

                Authors contributed equally to this work.

                [* ]Author to whom correspondence should be addressed; E-Mail: felicity.rose@ 123456nottingham.ac.uk ; Tel.: +44-115-846-7856.
                Article
                Publisher ID: materials-07-03106
                DOI: 10.3390/ma7043106
                PMC ID: 5453355
                PubMed ID: 28788609
                SO-VID: 6b543322-b63c-49f6-b8d7-1ec97852d730
                Copyright © © 2014 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 04 February 2014
                Date revision received : 17 March 2014
                Date accepted : 24 March 2014
                Categories
                Subject: Review

                Keywords: gelatin,tissue engineering,ophthalmology,biocompatibility,cornea,retinal epithelium
                Data availability:
                Keywords: gelatin, tissue engineering, ophthalmology, biocompatibility, cornea, retinal epithelium

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