In vitro effect of a corrosive hostile ocular surface on candidate biomaterials for keratoprosthesis skirt
Identifieur interne : 001713 ( Pmc/Checkpoint ); précédent : 001712; suivant : 001714In vitro effect of a corrosive hostile ocular surface on candidate biomaterials for keratoprosthesis skirt
Auteurs : Xiao Wei Tan [Singapour] ; Andri Riau [Singapour] ; Zhi Long Shi [Singapour] ; Anna C S. Tan [Singapour] ; Koon Gee Neoh [Singapour] ; Khiam Aik Khor [Singapour] ; Roger W. Beuerman [Singapour] ; Donald Tan [Singapour] ; Jodhbir S. Mehta [Singapour]Source :
- The British Journal of Ophthalmology [ 0007-1161 ] ; 2012.
Abstract
Keratoprosthesis (KPro) devices are prone to long-term corrosion and microbiological assault. The authors aimed to compare the inflammatory response and material dissolution properties of two candidate KPro skirt materials, hydroxyapatite (HA) and titania (TiO2) in a simulated in vitro cornea inflammation environment.
Lipopolysaccharide-stimulated cytokine secretions were evaluated with human corneal fibroblasts on both HA and TiO2. Material specimens were subjected to electrochemical and long-term incubation test with artificial tear fluid (ATF) of various acidities. Topography and surface roughness of material discs were analysed by scanning electron microscopy and atomic force microscopy.
There were less cytokines secreted from human corneal fibroblasts seeded on TiO2 substrates as compared with HA. TiO2 was more resistant to the corrosion effect caused by acidic ATF in contrast to HA. Moreover, the elemental composition of TiO2 was more stable than HA after long-term incubation with ATF.
TiO2 is more resistant to inflammatory degradation and has a higher corrosion resistance as compared with HA, and in this regard may be a suitable material to replace HA as an osteo-odonto-keratoprosthesis skirt. This would reduce resorption rates for KPro surgery.
Url:
DOI: 10.1136/bjophthalmol-2012-301633
PubMed: 22802307
PubMed Central: 3432489
Affiliations:
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Tan</name><affiliation wicri:level="1"><nlm:aff id="aff3">Singapore National Eye Centre, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Singapore National Eye Centre</wicri:regionArea></affiliation></author><author><name sortKey="Neoh, Koon Gee" sort="Neoh, Koon Gee" uniqKey="Neoh K" first="Koon Gee" last="Neoh">Koon Gee Neoh</name><affiliation wicri:level="4"><nlm:aff id="aff2">School of Chemical and Bimolecular Engineering, National University of Singapore, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>School of Chemical and Bimolecular Engineering, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation></author><author><name sortKey="Khor, Khiam Aik" sort="Khor, Khiam Aik" uniqKey="Khor K" first="Khiam Aik" last="Khor">Khiam Aik Khor</name><affiliation wicri:level="1"><nlm:aff id="aff4">School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>School of Mechanical and Aerospace Engineering, Nanyang Technological University</wicri:regionArea><wicri:noRegion>Nanyang Technological University</wicri:noRegion></affiliation></author><author><name sortKey="Beuerman, Roger W" sort="Beuerman, Roger W" uniqKey="Beuerman R" first="Roger W" last="Beuerman">Roger W. Beuerman</name><affiliation wicri:level="1"><nlm:aff id="aff1">Tissue Engineering and Stem Cell Research Group, Singapore Eye Research Institute, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Tissue Engineering and Stem Cell Research Group, Singapore Eye Research Institute</wicri:regionArea><wicri:noRegion>Singapore Eye Research Institute</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff5">Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">Duke-NUS SRP Neuroscience and Behavioral Disorders, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Duke-NUS SRP Neuroscience and Behavioral Disorders</wicri:regionArea></affiliation></author><author><name sortKey="Tan, Donald" sort="Tan, Donald" uniqKey="Tan D" first="Donald" last="Tan">Donald Tan</name><affiliation wicri:level="4"><nlm:aff id="aff2">School of Chemical and Bimolecular Engineering, National University of Singapore, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>School of Chemical and Bimolecular Engineering, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Singapore National Eye Centre, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Singapore National Eye Centre</wicri:regionArea></affiliation></author><author><name sortKey="Mehta, Jodhbir S" sort="Mehta, Jodhbir S" uniqKey="Mehta J" first="Jodhbir S" last="Mehta">Jodhbir S. Mehta</name><affiliation wicri:level="1"><nlm:aff id="aff1">Tissue Engineering and Stem Cell Research Group, Singapore Eye Research Institute, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Tissue Engineering and Stem Cell Research Group, Singapore Eye Research Institute</wicri:regionArea><wicri:noRegion>Singapore Eye Research Institute</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Singapore National Eye Centre, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Singapore National Eye Centre</wicri:regionArea></affiliation><affiliation wicri:level="4"><nlm:aff id="aff5">Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore</wicri:regionArea><orgName type="university">Université nationale de Singapour</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7">Department of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Clinical Sciences, Duke-NUS Graduate Medical School</wicri:regionArea><wicri:noRegion>Duke-NUS Graduate Medical School</wicri:noRegion></affiliation></author></analytic><series><title level="j">The British Journal of Ophthalmology</title><idno type="ISSN">0007-1161</idno><idno type="eISSN">1468-2079</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Aim</title><p>Keratoprosthesis (KPro) devices are prone to long-term corrosion and microbiological assault. The authors aimed to compare the inflammatory response and material dissolution properties of two candidate KPro skirt materials, hydroxyapatite (HA) and titania (TiO<sub>2</sub>) in a simulated in vitro cornea inflammation environment.</p></sec><sec><title>Methods</title><p>Lipopolysaccharide-stimulated cytokine secretions were evaluated with human corneal fibroblasts on both HA and TiO<sub>2</sub>. Material specimens were subjected to electrochemical and long-term incubation test with artificial tear fluid (ATF) of various acidities. Topography and surface roughness of material discs were analysed by scanning electron microscopy and atomic force microscopy.</p></sec><sec><title>Results</title><p>There were less cytokines secreted from human corneal fibroblasts seeded on TiO<sub>2</sub> substrates as compared with HA. TiO<sub>2</sub> was more resistant to the corrosion effect caused by acidic ATF in contrast to HA. Moreover, the elemental composition of TiO<sub>2</sub> was more stable than HA after long-term incubation with ATF.</p></sec><sec><title>Conclusions</title><p>TiO<sub>2</sub> is more resistant to inflammatory degradation and has a higher corrosion resistance as compared with HA, and in this regard may be a suitable material to replace HA as an osteo-odonto-keratoprosthesis skirt. This would reduce resorption rates for KPro surgery.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Liu, C" uniqKey="Liu C">C Liu</name></author><author><name sortKey="Paul, B" uniqKey="Paul B">B Paul</name></author><author><name sortKey="Tandon, R" uniqKey="Tandon R">R Tandon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tan, Dt" uniqKey="Tan D">DT Tan</name></author><author><name sortKey="Tay, Ab" uniqKey="Tay A">AB Tay</name></author><author><name sortKey="Theng, Jt" uniqKey="Theng J">JT Theng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tay, Ab" uniqKey="Tay A">AB Tay</name></author><author><name sortKey="Tan, Dt" uniqKey="Tan D">DT Tan</name></author><author><name sortKey="Lye, Kw" uniqKey="Lye K">KW Lye</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Falcinelli, G" uniqKey="Falcinelli G">G Falcinelli</name></author><author><name sortKey="Falsini, B" uniqKey="Falsini B">B Falsini</name></author><author><name sortKey="Taloni, M" uniqKey="Taloni M">M Taloni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hille, K" uniqKey="Hille K">K Hille</name></author><author><name sortKey="Landau, H" uniqKey="Landau H">H Landau</name></author><author><name sortKey="Ruprecht, Kw" uniqKey="Ruprecht K">KW Ruprecht</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Iyer, G" uniqKey="Iyer G">G Iyer</name></author><author><name sortKey="Pillai, Vs" uniqKey="Pillai V">VS Pillai</name></author><author><name sortKey="Srinivasan, B" uniqKey="Srinivasan B">B Srinivasan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Akpek, Ek" uniqKey="Akpek E">EK Akpek</name></author><author><name sortKey="Gottsch, Jd" uniqKey="Gottsch J">JD Gottsch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ueta, M" uniqKey="Ueta M">M Ueta</name></author><author><name sortKey="Kinoshita, S" uniqKey="Kinoshita S">S Kinoshita</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ueta, M" uniqKey="Ueta M">M Ueta</name></author><author><name sortKey="Kinoshita, S" uniqKey="Kinoshita S">S Kinoshita</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Polack, Fm" uniqKey="Polack F">FM Polack</name></author><author><name sortKey="Heimke, G" uniqKey="Heimke G">G Heimke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mehta, Js" uniqKey="Mehta J">JS Mehta</name></author><author><name sortKey="Futter, Ce" uniqKey="Futter C">CE Futter</name></author><author><name sortKey="Sandeman, Sr" uniqKey="Sandeman S">SR Sandeman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pullamsetti, Ss" uniqKey="Pullamsetti S">SS Pullamsetti</name></author><author><name sortKey="Savai, R" uniqKey="Savai R">R Savai</name></author><author><name sortKey="Janssen, W" uniqKey="Janssen W">W Janssen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Punnia Moorthy, A" uniqKey="Punnia Moorthy A">A Punnia-Moorthy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tan, Xw" uniqKey="Tan X">XW Tan</name></author><author><name sortKey="Perera, Ap" uniqKey="Perera A">AP Perera</name></author><author><name sortKey="Tan, A" uniqKey="Tan A">A Tan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ament, Jd" uniqKey="Ament J">JD Ament</name></author><author><name sortKey="Spurr Michaud, Sj" uniqKey="Spurr Michaud S">SJ Spurr-Michaud</name></author><author><name sortKey="Dohlman, Ch" uniqKey="Dohlman C">CH Dohlman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Anwar, Em" uniqKey="Anwar E">EM Anwar</name></author><author><name sortKey="Kheiralla, Ls" uniqKey="Kheiralla L">LS Kheiralla</name></author><author><name sortKey="Tammam, Rh" uniqKey="Tammam R">RH Tammam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yu, Wq" uniqKey="Yu W">WQ Yu</name></author><author><name sortKey="Qiu, J" uniqKey="Qiu J">J Qiu</name></author><author><name sortKey="Zhang, Fq" uniqKey="Zhang F">FQ Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, Hh" uniqKey="Huang H">HH Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alexeev, Vl" uniqKey="Alexeev V">VL Alexeev</name></author><author><name sortKey="Das, S" uniqKey="Das S">S Das</name></author><author><name sortKey="Finegold, Dn" uniqKey="Finegold D">DN Finegold</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yuan, Sj" uniqKey="Yuan S">SJ Yuan</name></author><author><name sortKey="Pehkonen, So" uniqKey="Pehkonen S">SO Pehkonen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Viitala, R" uniqKey="Viitala R">R Viitala</name></author><author><name sortKey="Franklin, V" uniqKey="Franklin V">V Franklin</name></author><author><name sortKey="Green, D" uniqKey="Green D">D Green</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Laattala, K" uniqKey="Laattala K">K Laattala</name></author><author><name sortKey="Huhtinen, R" uniqKey="Huhtinen R">R Huhtinen</name></author><author><name sortKey="Puska, M" uniqKey="Puska M">M Puska</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bazan, He" uniqKey="Bazan H">HE Bazan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fukuda, K" uniqKey="Fukuda K">K Fukuda</name></author><author><name sortKey="Kumagai, N" uniqKey="Kumagai N">N Kumagai</name></author><author><name sortKey="Fujitsu, Y" uniqKey="Fujitsu Y">Y Fujitsu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cubitt, Cl" uniqKey="Cubitt C">CL Cubitt</name></author><author><name sortKey="Lausch, Rn" uniqKey="Lausch R">RN Lausch</name></author><author><name sortKey="Oakes, Je" uniqKey="Oakes J">JE Oakes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hong, Jw" uniqKey="Hong J">JW Hong</name></author><author><name sortKey="Liu, Jj" uniqKey="Liu J">JJ Liu</name></author><author><name sortKey="Lee, Js" uniqKey="Lee J">JS Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thakur, A" uniqKey="Thakur A">A Thakur</name></author><author><name sortKey="Willcox, Md" uniqKey="Willcox M">MD Willcox</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Andersson, Se" uniqKey="Andersson S">SE Andersson</name></author><author><name sortKey="Lexmuller, K" uniqKey="Lexmuller K">K Lexmuller</name></author><author><name sortKey="Johansson, A" uniqKey="Johansson A">A Johansson</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Br J Ophthalmol</journal-id><journal-id journal-id-type="iso-abbrev">Br J Ophthalmol</journal-id><journal-id journal-id-type="publisher-id">bjo</journal-id><journal-id journal-id-type="hwp">bjophthalmol</journal-id><journal-title-group><journal-title>The British Journal of Ophthalmology</journal-title></journal-title-group><issn pub-type="ppub">0007-1161</issn><issn pub-type="epub">1468-2079</issn><publisher><publisher-name>BMJ Group</publisher-name><publisher-loc>BMA House, Tavistock Square, London, WC1H 9JR</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22802307</article-id><article-id pub-id-type="pmc">3432489</article-id><article-id pub-id-type="publisher-id">bjophthalmol-2012-301633</article-id><article-id pub-id-type="doi">10.1136/bjophthalmol-2012-301633</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Articles</subject></subj-group><subj-group subj-group-type="hwp-journal-coll"><subject>1506</subject></subj-group><series-title>Laboratory science</series-title></article-categories><title-group><article-title>In vitro effect of a corrosive hostile ocular surface on candidate biomaterials for keratoprosthesis skirt</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Tan</surname><given-names>Xiao Wei</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Riau</surname><given-names>Andri</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Shi</surname><given-names>Zhi Long</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Tan</surname><given-names>Anna C S</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Neoh</surname><given-names>Koon Gee</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Khor</surname><given-names>Khiam Aik</given-names></name><xref ref-type="aff" rid="aff4">4</xref></contrib><contrib contrib-type="author"><name><surname>Beuerman</surname><given-names>Roger W</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff5">5</xref><xref ref-type="aff" rid="aff6">6</xref></contrib><contrib contrib-type="author"><name><surname>Tan</surname><given-names>Donald</given-names></name><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Mehta</surname><given-names>Jodhbir S</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff3">3</xref><xref ref-type="aff" rid="aff5">5</xref><xref ref-type="aff" rid="aff7">7</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Tissue Engineering and Stem Cell Research Group, Singapore Eye Research Institute, Singapore</aff><aff id="aff2"><label>2</label>School of Chemical and Bimolecular Engineering, National University of Singapore, Singapore</aff><aff id="aff3"><label>3</label>Singapore National Eye Centre, Singapore</aff><aff id="aff4"><label>4</label>School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore</aff><aff id="aff5"><label>5</label>Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore</aff><aff id="aff6"><label>6</label>Duke-NUS SRP Neuroscience and Behavioral Disorders, Singapore</aff><aff id="aff7"><label>7</label>Department of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore</aff><author-notes><corresp><label>Correspondence to</label> Professor Jodhbir S Mehta, Singapore Eye Research Institute, 11 Third Hospital Drive, Singapore 168751, Singapore; <email>jodmehta@gmail.com</email></corresp><fn fn-type="other"><p>Additional materials are published online only. To view these files please visit the journal online (<ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.1136/bjophthalmol-2012-301633">http://dx.doi.org/10.1136/bjophthalmol-2012-301633</ext-link>).</p></fn></author-notes><pub-date pub-type="ppub"><month>9</month><year>2012</year></pub-date><volume>96</volume><issue>9</issue><fpage>1252</fpage><lpage>1258</lpage><history><date date-type="accepted"><day>16</day><month>6</month><year>2012</year></date></history><permissions><copyright-statement>© 2012, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.</copyright-statement><copyright-year>2012</copyright-year><license license-type="open-access"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/2.0/">http://creativecommons.org/licenses/by-nc/2.0/</ext-link> and <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/2.0/legalcode">http://creativecommons.org/licenses/by-nc/2.0/legalcode</ext-link>.</license-p></license></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="bjophthalmol-2012-301633.pdf"></self-uri><abstract><sec><title>Aim</title><p>Keratoprosthesis (KPro) devices are prone to long-term corrosion and microbiological assault. The authors aimed to compare the inflammatory response and material dissolution properties of two candidate KPro skirt materials, hydroxyapatite (HA) and titania (TiO<sub>2</sub>) in a simulated in vitro cornea inflammation environment.</p></sec><sec><title>Methods</title><p>Lipopolysaccharide-stimulated cytokine secretions were evaluated with human corneal fibroblasts on both HA and TiO<sub>2</sub>. Material specimens were subjected to electrochemical and long-term incubation test with artificial tear fluid (ATF) of various acidities. Topography and surface roughness of material discs were analysed by scanning electron microscopy and atomic force microscopy.</p></sec><sec><title>Results</title><p>There were less cytokines secreted from human corneal fibroblasts seeded on TiO<sub>2</sub> substrates as compared with HA. TiO<sub>2</sub> was more resistant to the corrosion effect caused by acidic ATF in contrast to HA. Moreover, the elemental composition of TiO<sub>2</sub> was more stable than HA after long-term incubation with ATF.</p></sec><sec><title>Conclusions</title><p>TiO<sub>2</sub> is more resistant to inflammatory degradation and has a higher corrosion resistance as compared with HA, and in this regard may be a suitable material to replace HA as an osteo-odonto-keratoprosthesis skirt. This would reduce resorption rates for KPro surgery.</p></sec></abstract><kwd-group><kwd>OOKP</kwd><kwd>microbial infection</kwd><kwd>material dissolution</kwd><kwd>artificial tear fluid</kwd><kwd>cornea</kwd><kwd>biochemistry</kwd><kwd>prosthesis</kwd><kwd>microbiology</kwd><kwd>contact lens</kwd><kwd>stem cells</kwd><kwd>lens and zonules</kwd><kwd>treatment surgery</kwd><kwd>epidemiology</kwd><kwd>experimental and animal models</kwd><kwd>ocular surface</kwd><kwd>genetics</kwd><kwd>imaging</kwd><kwd>treatment lasers</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>special-feature</meta-name><meta-value>unlocked</meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec><title>Introduction</title><p>Osteo-odonto-keratoprosthesis (OOKP) is a complicated form of ocular surface reconstruction surgery involving removal of a patient's autologous tooth to support an optical cylinder.<xref ref-type="bibr" rid="b1 b2 b3 b4">1–4</xref> The OOKP procedure is performed for patients with end-stage ocular surface diseases and severe inflammatory or dry eye states when corneal transplant or other keratoprosthesis (KPro) devices such as the Boston KPro Type I are contraindicated.<xref ref-type="bibr" rid="b1">1</xref><xref ref-type="bibr" rid="b3">3</xref> However, autologous OOKP surgery cannot be performed when there are no viable canine teeth. Using allograft donor teeth are more prone to lamina resorption, and there are complications related to the use of a bone lamina as a prosthetic skirt including aseptic loosening, bone absorption and limited size of optical field due to the limitations of tooth dimensions. The most severe complication is related to the chronic ocular surface inflammation which can lead to the partial or complete absorption of the bone and tooth implants.<xref ref-type="bibr" rid="b5">5</xref><xref ref-type="bibr" rid="b6">6</xref> Development of a synthetic substitute for the autologous tooth-bone lamina would therefore be a potential substitute for the OOKP procedure and would also have the added benefit of not requiring the extensive surgery required to remove a canine tooth from the patient.</p><p>The ocular surface epithelium not only forms a physical barrier to the external environment but also serves as a non-specific innate immune system against microbes.<xref ref-type="bibr" rid="b7">7</xref> In patients with severe ocular surface disease, there is a disruption of the normal innate immunity and a change in the normal commensal flora.<xref ref-type="bibr" rid="b8">8</xref><xref ref-type="bibr" rid="b9">9</xref> This produces an unstable ocular surface sensitive to the new microbial flora leading to chronic ocular inflammation and these processes are further exacerbated by a poor tear film in these patients.<xref ref-type="bibr" rid="b8">8</xref> Therefore any prosthetic device must be able to withstand the unstable ocular surface microenvironment with its continual changing flora and chronic inflammation in these adverse conditions.</p><p>It would therefore be advantageous if prospective synthetic KPro skirt devices are able to reduce the incidence of bacterial contamination during implantation as well as maintain excellent tissue biocompatibility in the milieu of an unstable microbial infection. Hydroxyapatite (HA) is a commonly used synthetic biomaterial which has some properties akin to the tooth and bone lamina used in OOKP surgery.<xref ref-type="bibr" rid="b10">10</xref> HA has excellent biocompatibility with human cornea stroma fibroblasts<xref ref-type="bibr" rid="b11">11</xref> but is prone to resorption after long-term implantation that can affect the device stability. Biomaterials with improved corrosion resistance at an inflammatory induced microenvironment may offer a more attractive solution. Both acute and chronic inflammatory states are associated with reduced tissue pH due to the high metabolic activities of inflammatory cells or bacteria.<xref ref-type="bibr" rid="b12">12</xref><xref ref-type="bibr" rid="b13">13</xref> Therefore, the ideal substitute should possess a high corrosion resistance to an inflammatory milieu in an acidic environment. Titania (TiO<sub>2</sub>) has been previously shown to have good biocompatibility with human corneal stroma fibroblasts and epithelial cells.<xref ref-type="bibr" rid="b14">14</xref><xref ref-type="bibr" rid="b15">15</xref> In addition TiO<sub>2</sub> has a protective layer of oxide film that is stable, bioinert and provides the material with resistance to corrosion in tissue fluids for example, artificial saliva.<xref ref-type="bibr" rid="b16">16</xref><xref ref-type="bibr" rid="b17">17</xref> These properties make TiO<sub>2</sub> a potential substitute to HA as a synthetic OOKP skirt material.</p><p>In this study, we aimed to compare the effect of microbial infection on two candidate keratoprosthetic materials, HA and TiO<sub>2</sub>. We also aimed to compare the corrosive properties of the materials with an electro-polarisation test and a long-term incubation model. These were performed in artificial tear fluid (ATF) with various acidities to simulate the acidic microenvironment which may occur in a milieu of chronic ocular inflammation.</p></sec><sec sec-type="materials|methods"><title>Materials and methods</title><sec><title>Material synthesis</title><p>HA discs were produced by spark plasma sintering HA powder at a nominal pressure of 50 MPa and sintering at 1000°C. TiO<sub>2</sub> discs were produced by spark plasma sintering TiO<sub>2</sub> powder at a pressure of 38 MPa and sintering at 1100°C. The diameters of all discs were 10 mm and the thicknesses were 2 mm.</p></sec><sec><title>Human corneal fibroblasts preparation</title><p>Human corneal stroma was collected from donor corneal tissue. The stroma tissue was cut into small pieces and cultured with the fibroblast growth medium (10% fetal bovine serum in Dulbecco's Modified Eagle Medium) changed every 2–3 days. All studies related to human tissues were approved by the Institutional Review Board of the Singapore Eye Research Institute and Singapore National Eye Centre.</p></sec><sec><title>Cytokine array</title><p>For cytokine array, corneal stroma fibroblasts (1×10<sup>4</sup>/cm<sup>2</sup>) in a 30 μl droplet were seeded on the surface of the substrate discs (<italic>n</italic>=3). At 24 h after seeding, culture medium was changed into serum-free medium containing lipopolysaccharide (LPS, 10 ng/ml). Twenty-four hours after addition of LPS, supernatant was collected for Bio-plex Pro Human cytokine 27-plex assay following the standard protocol provided by the vendor (Bio-rad, Berkeley, California, USA). Cytokine analysis of culture medium from cells grown on a glass cover slip was used as a positive control.</p></sec><sec><title>Electrochemical test</title><p>Electrochemical tests were carried out in an Autolab-PGSTAT30 (Metrohm Autolab, the Netherlands) at room temperature in a conventional 3-electrode cell.<xref ref-type="bibr" rid="b18">18</xref> ATF solution (0.85 mg/ml lysozyme, 1.82 mg/ml bovine serum albumin, 5 mmol/l urea, 100 mmol/l NaCl, 26 mmol/l Na<sub>2</sub>HCO<sub>3</sub>, 16 mmol/l KCl, 31 μmol/l citric acid) was made for the immersion of the discs. The pH was adjusted to 6.5 and 5 by the addition of HCl solution.<xref ref-type="bibr" rid="b19">19</xref> The test was performed with graded sequential incremental potential from -5000 to 5000 mV (saturated calomel electrode) at a scan rate of 10 mV/s.</p></sec><sec><title>Long-term corrosion test with simulated tear fluid</title><p>Material discs were incubated in the 50 ml ATF solution (37°C) continuously for 3 months on a shaker at 60 rpm. The solution was changed once every week. The material discs were then washed in double-distilled water (37°C) for 1 week with the water changed once every 2 days.</p></sec><sec><title>Scanning electronic microscopy (SEM) and atomic force microscopy (AFM)</title><p>The material discs were coated with a layer of gold by the sputter coating machine (BAL-TEC, Germany). Images of the surface of the substrates were scanned with SEM (JEOL 5600LV, Japan). AFM scanning (Veeco, California, USA) was performed with the tapping mode in air (room temperature). The scan rate was 0.5 Hz/s. To quantify the effect of pitting corrosion, six different areas were randomly selected on each material substrate. Dimensional topography and surface roughness were measured with the software provided by the vendor (Nanoscope 6.11 R1, Veeco, CA, USA). The average roughness (<italic>Ra</italic>) of AFM image represents the average pitting corrosion depth.<xref ref-type="bibr" rid="b20">20</xref></p></sec></sec><sec sec-type="results"><title>Results</title><sec><title>Material mediated cellular reaction discrepancy to LPS</title><p>The cytokine expression profile indicated that corneal fibroblasts grown on the different materials continuously released several cytokines: Interleukin (IL)-1rα, IL-4, IL-6, IL-9, basic fibroblastic growth factor, granulocyte colony-stimulating factor (G-CSF), granulocytes macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-r, IFN γ induced protein-10, macrophage inflammatory protein (MIP)-1α, MIP-1b, regulated on activation normal T cell expressed and secreted, tumour necrosis factor (TNF)-α, and vascular endothelial growth factor into the culture medium, and the secretions were increased following LPS stimulation. After normalisation of the cytokine expression level to the control, the data showed that there were less cytokines (IFN-g, IL-1rα, basic fibroblastic growth factor, vascular endothelial growth factor, GM-CSF, induced protein -10, G-CSF, IL-4, IL-6, TNF-α, MIP-1α) stimulated by LPS from corneal fibroblasts on TiO<sub>2</sub> substrates than HA (<xref ref-type="fig" rid="fig1">figure 1</xref>).</p><fig id="fig1" position="float"><label>Figure 1</label><caption><p>Fold change of cytokine expression level at the material surface of lipopolysaccharide (LPS)-stimulated human cornea fibroblasts. All data are relative to the readings of their individual group without LPS treatment. Data are represented as mean ± SE. *p<0.05 between hydroxyapatite (HA) and (titania) TiO<sub>2.</sub> bFGF: basic fibroblastic growth factor, G-CSF: granulocyte colony-stimulating factor, GM-CSF: granulocytes macrophage colony-stimulating factor, GS: glass slide. <italic>n</italic>=6, IFN: interferon, IL: interleukin, IP: induced protein, MIP: macrophage inflammatory protein, TNF: tumour necrosis factor, VEGF: vascular endothelial growth factor.</p></caption><graphic xlink:href="bjophthalmol-2012-301633fig1"></graphic></fig></sec><sec><title>Assessment of surface corrosion after electrochemical test</title><p>Untreated HA whose topography was qualitatively assessed by SEM (<xref ref-type="fig" rid="fig2">figure 2A1</xref>) exhibited a smooth and pit-free surface. After electro-polarisation testing with ATF (pH 6.5), clusters of deep pits were found on the surface of HA discs (<xref ref-type="fig" rid="fig2">figure 2A2</xref>). After testing with acidic ATF (pH 5), the surface of the HA disc was seen to be unevenly damaged with HA particles exposed to the air (<xref ref-type="fig" rid="fig2">figure 2A3</xref>). SEM images of untreated TiO<sub>2</sub> exhibited a surface of uneven ridges (<xref ref-type="fig" rid="fig2">figure 2B1</xref>). After electro-polarisation in ATF (pH 6.5), there were some shallow pits on the surface of TiO<sub>2</sub> that were less in nature and not as clearly defined as those on HA (<xref ref-type="fig" rid="fig2">figure 2B2</xref>). After electro-polarisation in pH 5 ATF, there was no qualitative increase in the amount of pits on the surface of TiO<sub>2</sub> (<xref ref-type="fig" rid="fig2">figure 2B3</xref>).</p><fig id="fig2" position="float"><label>Figure 2</label><caption><p>Representative scanning electronic microscopy (SEM) images of hydroxyapatite (HA) and titania (TiO<sub>2</sub>) for electrochemical test. A<sub>1–3</sub>: HA; B<sub>1–3</sub>: TiO<sub>2</sub>. A<sub>1</sub> and B<sub>1</sub>: Before treatment; A<sub>2</sub> and B<sub>2</sub>: After electrochemical test in artificial tear fluid at pH 6.5; A<sub>3</sub> and B<sub>3</sub>: After electrochemical test in artificial tear fluid at pH 5. The scale bar in all images is 10 μm.</p></caption><graphic xlink:href="bjophthalmol-2012-301633fig2"></graphic></fig><p>The depths of pits, cleavages and the overall corrosion severity were quantitatively assessed by the 3D topography of AFM. Representative topography was captured from each substrate after electro-polarisation in ATF. No obvious pits could be observed on the normal HA samples (<xref ref-type="fig" rid="fig3">figure 3A1</xref>). The material surface became uneven after electrochemical testing with ATF (pH 6.5, <xref ref-type="fig" rid="fig3">figure 3A2</xref>). The surface roughness significantly increased on the HA discs after electro-polarisation with acidic ATF (pH=5, <xref ref-type="fig" rid="fig3">figure 3A3</xref>). The 3D topography of TiO<sub>2</sub> showed no obvious change of surface roughness after ATF treatment at either pH (<xref ref-type="fig" rid="fig3">figure 3A4–A6</xref>). Following the capture of topography with each tear fluid, the mean depth of the surface roughness (<italic>Ra</italic>) was calculated. <italic>Ra</italic> of untreated HA was 23.1±1.1 nm. After electro-polarisation with pH 6.5 ATF, the <italic>Ra</italic> increased to 34.1±13.4 nm. After electro-polarisation with pH 5 ATF, <italic>Ra</italic> of HA specimens increased around twofold and reached as high as 78.7±13.2 nm. The <italic>Ra</italic> of untreated TiO<sub>2</sub> specimen was 90.8±16.8 nm and showed no significant change after electro-polarisation with pH 6.5 ATF or pH 5 ATF (<italic>Ra</italic>=121.8±11.4 nm and 83.3±20.8 nm respectively, p>0.05). After normalisation to the untreated HA or TiO<sub>2</sub>, the fold changes of <italic>Ra</italic> were plotted in <xref ref-type="fig" rid="fig4">figure 4C</xref>.</p><fig id="fig3" position="float"><label>Figure 3</label><caption><p>Atomic force microscopy (AFM) scanning and data analysing of hydroxyapatite (HA) and titania (TiO<sub>2</sub>) for electrochemical test. A: Representative 3D topography of material discs. A<sub>1–3</sub>: HA; A<sub>4–6</sub>: TiO<sub>2</sub>. A<sub>1</sub> and A<sub>4</sub>: Before treatment; A<sub>2</sub> and A<sub>5</sub>: After electrochemical test in artificial tear fluid at pH 6.5; A<sub>3</sub> and A<sub>6</sub>: After electrochemical test in artificial tear fluid at pH 5. B: Histogram showing the relationship of average roughness (<italic>Ra</italic>) with pH value of artificial tear fluid. All data are normalised to untreated specimens and represented as mean ± SE. <italic>n</italic>=12.</p></caption><graphic xlink:href="bjophthalmol-2012-301633fig3"></graphic></fig><fig id="fig4" position="float"><label>Figure 4</label><caption><p>Representative scanning electronic microscopy (SEM) images of hydroxyapatite (HA) and titania (TiO<sub>2</sub>) for long-term corrosion test. A<sub>1–3</sub>: HA; B<sub>1–3</sub>: TiO<sub>2</sub>. A<sub>1</sub> and B<sub>1</sub>: Before treatment; A<sub>2</sub> and B<sub>2</sub>: After long-term incubation in artificial tear fluid at pH 6.5; A<sub>3</sub> and B<sub>3</sub>: After long-term incubation in artificial tear fluid at pH 5. The scale bar in all images is 10 μm.</p></caption><graphic xlink:href="bjophthalmol-2012-301633fig4"></graphic></fig></sec><sec><title>Assessment of surface corrosion after long-term incubation with ATF</title><p>After incubation with pH 6.5 ATF for 3 months, there was a high density of deep pits developed on the surface of HA (<xref ref-type="fig" rid="fig4">figure 4A2</xref>). After incubation with pH 5 ATF, there was severe disruption of the HA surface. Deep corrosion pits and cracks merged together with multiple HA particles being exposed on the surface (<xref ref-type="fig" rid="fig4">figure 4A3</xref>). For TiO<sub>2</sub> specimens, there was no obvious surface morphology change on SEM images after long-term incubation with ATF (pH 6.5 or pH 5) (<xref ref-type="fig" rid="fig4">figure 4B1–3</xref>).</p><p>The surface topography of material discs after long-term degradation test was also quantitatively assessed by AFM. The 3D topography of material discs after incubation with pH 6.5 ATF revealed that HA surface became very uneven (<xref ref-type="fig" rid="fig5">figure 5A2</xref>). The HA surface was extremely rough after incubation with pH 5 ATF (<xref ref-type="fig" rid="fig5">figure 5A3</xref>). The 3D topography of TiO<sub>2</sub> showed a non-significant increase of surface roughness after ATF incubation (<xref ref-type="fig" rid="fig5">figure 5A4–6</xref>).Surface <italic>Ra</italic> of untreated HA was 24.1±1.1 nm. After treatment with pH 6.5 ATF, the <italic>Ra</italic> significantly increased around twofold to 62.2±3.4 nm. The <italic>Ra</italic> of HA specimen significantly increased 12-fold and reached as high as 296±12.2 nm in pH 5 ATF. The <italic>Ra</italic> of TiO<sub>2</sub> specimen increased from 93.1±8.3 to 152.4±0.2 nm after incubation with pH 6.5 ATF and increased to 135±10.7 nm after treatment with pH 5 ATF. Both these increases were less than onefold compared to the untreated TiO<sub>2.</sub> The image depth readings were normalised to the untreated HA or TiO<sub>2</sub> samples and the fold changes of <italic>Ra</italic> were plotted in <xref ref-type="fig" rid="fig5">figure 5C</xref>.</p><fig id="fig5" position="float"><label>Figure 5</label><caption><p>Atomic force microscopy (AFM) scanning and data analysing of hydroxyapatite (HA) and titania (TiO<sub>2</sub>) for long-term corrosion test. A: Representative 3D topography of material discs. A<sub>1–3</sub>: HA; A<sub>4–6</sub>: TiO<sub>2</sub>. A<sub>1</sub> and A<sub>4</sub>: Before treatment; A<sub>2</sub> and A<sub>5</sub>: After long-term corrosion test in artificial tear fluid at pH 6.5; A<sub>3</sub> and A<sub>6</sub>: After long-term corrosion test in artificial tear fluid at pH 5. B: Histogram showing the relationship of average roughness (<italic>Ra</italic>) with pH value of artificial tear fluid. All data are normalised to untreated specimens and represented as mean ± SE. <italic>n</italic>=12.</p></caption><graphic xlink:href="bjophthalmol-2012-301633fig5"></graphic></fig></sec></sec><sec sec-type="discussion"><title>Discussion</title><p>There are currently few studies evaluating the dissolution properties of prospective artificial corneal skirt devices.<xref ref-type="bibr" rid="b21">21</xref><xref ref-type="bibr" rid="b22">22</xref> One of the issues in OOKP surgery is resorption. This can lead to leakage around the optic cylinder which in turn can predispose to microbiological infection and the risk of the resorbed lamina harbouring organisms. In our designed synthetic OOKP device, the optic will be sealed to the haptic with the use of dental cement as in OOKP, thereby reducing the possibilities of an intraocular infection. Ideally our study would have a comparative group consisting of osteodental lamina, even though synthetic HA and osteodental lamina are not totally comparable in all respects. The mineral constituents of synthetic HA and osteodental lamina are comparable. Both of them are made of calcium apatite with the formula Ca(n)(PO4)(n)(OH)(n). Hence they share some similar physical and chemical properties. That is why we and others<xref ref-type="bibr" rid="b21">21</xref> have used HA as control group. Comparison studies with human cadaver osteodental lamina would have been more informative but currently we have no such resources and it will be our future work.</p><p>We analysed the inflammatory cellular response and dissolution properties of HA and TiO<sub>2</sub> in a simulated inhospitable ocular surface environment. LPS is a component of the cell membrane of gram-negative bacteria. Corneal fibroblasts are sensitive to LPS stimulation and this plays a role in the regulation of cornea inflammation secondary to bacterial infection. LPS has been shown to induce the release of the pro-inflammatory cytokine IL-6 and chemokines G-CSF, monocyte chemotactic protein-1, MIP-1β, IL-8 and intercellular adhesion molecule-1 by corneal fibroblasts.<xref ref-type="bibr" rid="b23">23</xref><xref ref-type="bibr" rid="b24">24</xref> Likewise infectious corneal ulcers are associated with the production of pro-inflammatory cytokines, such as IL-1, TNF-α and chemokines such as GM-CSF by resident human corneal fibroblasts.<xref ref-type="bibr" rid="b25 b26 b27">25–27</xref> Such a response in vivo would trigger local infiltration and activation of leucocytes and contribute to localised inflammation. In our studies, we found that LPS induced the production of a wide panel of cytokines/chemokines from cultured human corneal fibroblasts. We found that HA-grown keratocytes were more prone to LPS stimulated cytokines/chemokines secretion than TiO<sub>2</sub> (<xref ref-type="fig" rid="fig1">figure 1</xref>). The reasons that human cornea fibroblasts on TiO<sub>2</sub> substrates secreted less cytokine/chemokines than those from HA are not fully understood, but could simply represent the fact that TiO<sub>2</sub> presents a more bioinert surface as compared to HA. The difference in cytokine expression we detected was due to the intrinsic properties of the material substrates on the cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay excluded the possibility that this difference was due to cellular toxicity caused by LPS on the fibroblasts grown on either biomaterial substrates (supplementary figure). Our results suggest that TiO<sub>2</sub> fibroblasts are less responsive to LPS stimulated inflammation and hence may prove effective in reducing the propagation of an acute inflammatory response into a chronic one.</p><p>Following ischaemia and inflammation, there is a reduction in tissue pH.<xref ref-type="bibr" rid="b12">12</xref><xref ref-type="bibr" rid="b13">13</xref> The reported reduction in pH can vary from 0.1 to 2.0.<xref ref-type="bibr" rid="b28">28</xref> Therefore, to address the issue of implant device stability in an ocular inflammatory milieu, we compared the corrosion resistance properties of material specimens in ATF at a pH value of 6.5 and also at a more acidic pH (pH 5) to simulate an inhospitable ocular surface. We compared the corrosion resistance properties of TiO<sub>2</sub> and HA in an electric-polarisation facility. Bioactive HA has a low polarisability and electric conductivity hence it is not possible to compare the electrochemical index of HA directly with TiO<sub>2</sub>. Morphological changes after electrochemical treatment were analysed, and compared with HA. TiO<sub>2</sub> showed less degradation with electrochemical treatment at both pH 6.5 and pH 5 ATF (<xref ref-type="fig" rid="fig2">figures 2</xref> and <xref ref-type="fig" rid="fig3">3</xref>). We deduce that this may be due to the passive film formation at the interface between TiO<sub>2</sub> and ATF.</p><p>Our SEM and AFM data showed that in pH 6.5 ATF, both HA and TiO<sub>2</sub> developed some early signs of pitting corrosion formation and an increase in surface roughness (<xref ref-type="fig" rid="fig2">figure 2</xref> to <xref ref-type="fig" rid="fig5">figure 5</xref>). However, the signs of corrosion in pH 5 ATF were remarkably different as TiO<sub>2</sub> showed smaller pits and a gradual increase in surface roughness while HA showed large pit formations and a steep increase in surface roughness (<xref ref-type="fig" rid="fig2">figure 2</xref> to <xref ref-type="fig" rid="fig5">figure 5</xref>). These observations indicated that, in a milieu of an acidic ocular tissue, TiO<sub>2</sub> is more resistant to corrosion as compared with HA.</p><p>Chronic inflammation plays an essential role in OOKP lamina degradation.<xref ref-type="bibr" rid="b5">5</xref><xref ref-type="bibr" rid="b6">6</xref> Hence, in our study we compared the corrosion resistance properties of HA and TiO<sub>2</sub> after long-term incubation with low pH ATF which stimulated a chronic ocular inflammation state. TiO<sub>2</sub> showed no significant degradation of surface morphology change while the surface of HA was severely damaged in both pH 6.5 and pH 5 ATF (<xref ref-type="fig" rid="fig4">figure 4</xref> and <xref ref-type="fig" rid="fig5">figure 5</xref>). The analysis of the elemental compositions showed that ‘Ca’ and ‘P’ were continuously released from HA while in contrast the elemental composition of TiO<sub>2</sub> was stable (Supplementary table). Therefore, our data again indicated that TiO<sub>2</sub> is more stable to long-term corrosion. TiO<sub>2</sub> might not undergo significant resorption in an adverse milieu and thereby may not lead to a leak in the KPro skirt area around the optical cylinder.</p><p>In conclusion, our studies involving cytokine array to compare the material mediated cellular reaction to inflammatory stimuli and studies evaluating the morphological changes of material substrates induced by acidic ATF show that TiO<sub>2</sub> is a promising skirt material for a fully synthetic OOKP device in terms of corrosion resistance to microbial infection and device stability.</p></sec></body><back><ack><p>The authors acknowledge funding (HREF/R684) from the Singapore Eye Research Institute and Shaw Foundation, Singapore.</p></ack><fn-group><fn fn-type="con"><p><bold>Contributors:</bold> (1) Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data: XWT, AR, ZLS, ACST, JSM. (2) Drafting the article or revising it critically for important intellectual content; XWT, KGN, DT, KAK, RWB, JSM. (3) Final approval of the version to be published: JSM.</p></fn><fn fn-type="financial-disclosure"><p><bold>Funding:</bold> This work was supported by Singapore Shaw's Foundation.</p></fn><fn fn-type="conflict"><p><bold>Competing interests:</bold> None.</p></fn><fn fn-type="other"><p><bold>Provenance and peer review:</bold> Not commissioned; externally peer reviewed.</p></fn></fn-group><ref-list><title>References</title><ref id="b1"><label>1</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liu</surname><given-names>C</given-names></name><name><surname>Paul</surname><given-names>B</given-names></name><name><surname>Tandon</surname><given-names>R</given-names></name><etal></etal></person-group><article-title>The osteo-odonto-keratoprosthesis (OOKP)</article-title>. <source>Semin Ophthalmol</source><year>2005</year>;<volume>20</volume>:<fpage>113</fpage>–<lpage>28</lpage><pub-id pub-id-type="pmid">16020351</pub-id></mixed-citation></ref><ref id="b2"><label>2</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tan</surname><given-names>DT</given-names></name><name><surname>Tay</surname><given-names>AB</given-names></name><name><surname>Theng</surname><given-names>JT</given-names></name><etal></etal></person-group><article-title>Keratoprosthesis surgery for end-stage corneal blindness in Asian eyes</article-title>. <source>Ophthalmology</source><year>2008</year>;<volume>115</volume>:<fpage>503</fpage>–<lpage>10.e3</lpage><pub-id pub-id-type="pmid">18319104</pub-id></mixed-citation></ref><ref id="b3"><label>3</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tay</surname><given-names>AB</given-names></name><name><surname>Tan</surname><given-names>DT</given-names></name><name><surname>Lye</surname><given-names>KW</given-names></name><etal></etal></person-group><article-title>Osteo-odonto-keratoprosthesis surgery: a combined ocular-oral procedure for ocular blindness</article-title>. <source>Int J Oral Maxillofac Surg</source><year>2007</year>;<volume>36</volume>:<fpage>807</fpage>–<lpage>13</lpage><pub-id pub-id-type="pmid">17630251</pub-id></mixed-citation></ref><ref id="b4"><label>4</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Falcinelli</surname><given-names>G</given-names></name><name><surname>Falsini</surname><given-names>B</given-names></name><name><surname>Taloni</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Modified osteo-odonto-keratoprosthesis for treatment of corneal blindness: long-term anatomical and functional outcomes in 181 cases</article-title>. <source>Arch Ophthalmol</source><year>2005</year>;<volume>123</volume>:<fpage>1319</fpage>–<lpage>29</lpage><pub-id pub-id-type="pmid">16219722</pub-id></mixed-citation></ref><ref id="b5"><label>5</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hille</surname><given-names>K</given-names></name><name><surname>Landau</surname><given-names>H</given-names></name><name><surname>Ruprecht</surname><given-names>KW</given-names></name></person-group><article-title>Osteo-odonto-keratoprosthesis. A summary of 6 years surgical experience</article-title>. <source>Ophthalmologe</source><year>2002</year>;<volume>99</volume>:<fpage>90</fpage>–<lpage>5</lpage><pub-id pub-id-type="pmid">11871079</pub-id></mixed-citation></ref><ref id="b6"><label>6</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Iyer</surname><given-names>G</given-names></name><name><surname>Pillai</surname><given-names>VS</given-names></name><name><surname>Srinivasan</surname><given-names>B</given-names></name><etal></etal></person-group><article-title>Modified osteo-odonto keratoprosthesis—the Indian experience—results of the first 50 cases</article-title>. <source>Cornea</source><year>2010</year>;<volume>29</volume>:<fpage>771</fpage>–<lpage>6</lpage><pub-id pub-id-type="pmid">20489578</pub-id></mixed-citation></ref><ref id="b7"><label>7</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Akpek</surname><given-names>EK</given-names></name><name><surname>Gottsch</surname><given-names>JD</given-names></name></person-group><article-title>Immune defense at the ocular surface</article-title>. <source>Eye (Lond)</source><year>2003</year>;<volume>17</volume>:<fpage>949</fpage>–<lpage>56</lpage><pub-id pub-id-type="pmid">14631402</pub-id></mixed-citation></ref><ref id="b8"><label>8</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ueta</surname><given-names>M</given-names></name><name><surname>Kinoshita</surname><given-names>S</given-names></name></person-group><article-title>Ocular surface inflammation mediated by innate immunity</article-title>. <source>Eye Contact Lens</source><year>2010</year>;<volume>36</volume>:<fpage>269</fpage>–<lpage>81</lpage><pub-id pub-id-type="pmid">20703156</pub-id></mixed-citation></ref><ref id="b9"><label>9</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ueta</surname><given-names>M</given-names></name><name><surname>Kinoshita</surname><given-names>S</given-names></name></person-group><article-title>Innate immunity of the ocular surface</article-title>. <source>Brain Res Bull</source><year>2010</year>;<volume>81</volume>:<fpage>219</fpage>–<lpage>28</lpage><pub-id pub-id-type="pmid">19828129</pub-id></mixed-citation></ref><ref id="b10"><label>10</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Polack</surname><given-names>FM</given-names></name><name><surname>Heimke</surname><given-names>G</given-names></name></person-group><article-title>Ceramic keratoprostheses</article-title>. <source>Ophthalmology</source><year>1980</year>;<volume>87</volume>:<fpage>693</fpage>–<lpage>8</lpage><pub-id pub-id-type="pmid">7402597</pub-id></mixed-citation></ref><ref id="b11"><label>11</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mehta</surname><given-names>JS</given-names></name><name><surname>Futter</surname><given-names>CE</given-names></name><name><surname>Sandeman</surname><given-names>SR</given-names></name><etal></etal></person-group><article-title>Hydroxyapatite promotes superior keratocyte adhesion and proliferation in comparison with current keratoprosthesis skirt materials</article-title>. <source>Br J Ophthalmol</source><year>2005</year>;<volume>89</volume>:<fpage>1356</fpage>–<lpage>62</lpage><pub-id pub-id-type="pmid">16170132</pub-id></mixed-citation></ref><ref id="b12"><label>12</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pullamsetti</surname><given-names>SS</given-names></name><name><surname>Savai</surname><given-names>R</given-names></name><name><surname>Janssen</surname><given-names>W</given-names></name><etal></etal></person-group><article-title>Inflammation, immunological reaction and role of infection in pulmonary hypertension</article-title>. <source>Clin Microbiol Infect</source><year>2011</year>;<volume>17</volume>:<fpage>7</fpage>–<lpage>14</lpage><pub-id pub-id-type="pmid">20545963</pub-id></mixed-citation></ref><ref id="b13"><label>13</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Punnia-Moorthy</surname><given-names>A</given-names></name></person-group><article-title>Evaluation of pH changes in inflammation of the subcutaneous air pouch lining in the rat, induced by carrageenan, dextran and Staphylococcus aureus</article-title>. <source>J Oral Pathol</source><year>1987</year>;<volume>16</volume>:<fpage>36</fpage>–<lpage>44</lpage><pub-id pub-id-type="pmid">2435877</pub-id></mixed-citation></ref><ref id="b14"><label>14</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tan</surname><given-names>XW</given-names></name><name><surname>Perera</surname><given-names>AP</given-names></name><name><surname>Tan</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Comparison of candidate materials for a synthetic osteo-odonto keratoprosthesis device</article-title>. <source>Invest Ophthalmol Vis Sci</source><year>2011</year>;<volume>52</volume>:<fpage>21</fpage>–<lpage>9</lpage><pub-id pub-id-type="pmid">20739467</pub-id></mixed-citation></ref><ref id="b15"><label>15</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ament</surname><given-names>JD</given-names></name><name><surname>Spurr-Michaud</surname><given-names>SJ</given-names></name><name><surname>Dohlman</surname><given-names>CH</given-names></name><etal></etal></person-group><article-title>The Boston Keratoprosthesis: comparing corneal epithelial cell compatibility with titanium and PMMA</article-title>. <source>Cornea</source><year>2009</year>;<volume>28</volume>:<fpage>808</fpage>–<lpage>11</lpage><pub-id pub-id-type="pmid">19574903</pub-id></mixed-citation></ref><ref id="b16"><label>16</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Anwar</surname><given-names>EM</given-names></name><name><surname>Kheiralla</surname><given-names>LS</given-names></name><name><surname>Tammam</surname><given-names>RH</given-names></name></person-group><article-title>Effect of fluoride on the corrosion behavior of Ti and Ti6Al4V dental implants coupled with different superstructures</article-title>. <source>J Oral Implantol</source><year>2011</year>;<volume>37</volume>:<fpage>309</fpage>–<lpage>17</lpage><pub-id pub-id-type="pmid">20545548</pub-id></mixed-citation></ref><ref id="b17"><label>17</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yu</surname><given-names>WQ</given-names></name><name><surname>Qiu</surname><given-names>J</given-names></name><name><surname>Zhang</surname><given-names>FQ</given-names></name></person-group><article-title>In vitro corrosion study of different TiO2 nanotube layers on titanium in solution with serum proteins</article-title>. <source>Colloids Surf B Biointerfaces</source><year>2011</year>;<volume>84</volume>:<fpage>400</fpage>–<lpage>5</lpage><pub-id pub-id-type="pmid">21377339</pub-id></mixed-citation></ref><ref id="b18"><label>18</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>HH</given-names></name></person-group><article-title>Surface characterizations and corrosion resistance of nickel-titanium orthodontic archwires in artificial saliva of various degrees of acidity</article-title>. <source>J Biomed Mater Res A</source><year>2005</year>;<volume>74</volume>:<fpage>629</fpage>–<lpage>39</lpage><pub-id pub-id-type="pmid">16025472</pub-id></mixed-citation></ref><ref id="b19"><label>19</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Alexeev</surname><given-names>VL</given-names></name><name><surname>Das</surname><given-names>S</given-names></name><name><surname>Finegold</surname><given-names>DN</given-names></name><etal></etal></person-group><article-title>Photonic crystal glucose-sensing material for noninvasive monitoring of glucose in tear fluid</article-title>. <source>Clin Chem</source><year>2004</year>;<volume>50</volume>:<fpage>2353</fpage>–<lpage>60</lpage><pub-id pub-id-type="pmid">15459093</pub-id></mixed-citation></ref><ref id="b20"><label>20</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yuan</surname><given-names>SJ</given-names></name><name><surname>Pehkonen</surname><given-names>SO</given-names></name></person-group><article-title>Microbiologically influenced corrosion of 304 stainless steel by aerobic Pseudomonas NCIMB 2021 bacteria: AFM and XPS study</article-title>. <source>Colloids Surf B Biointerfaces</source><year>2007</year>;<volume>59</volume>:<fpage>87</fpage>–<lpage>99</lpage><pub-id pub-id-type="pmid">17582747</pub-id></mixed-citation></ref><ref id="b21"><label>21</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Viitala</surname><given-names>R</given-names></name><name><surname>Franklin</surname><given-names>V</given-names></name><name><surname>Green</surname><given-names>D</given-names></name><etal></etal></person-group><article-title>Towards a synthetic osteo-odonto-keratoprosthesis</article-title>. <source>Acta Biomater</source><year>2009</year>;<volume>5</volume>:<fpage>438</fpage>–<lpage>52</lpage><pub-id pub-id-type="pmid">18706878</pub-id></mixed-citation></ref><ref id="b22"><label>22</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Laattala</surname><given-names>K</given-names></name><name><surname>Huhtinen</surname><given-names>R</given-names></name><name><surname>Puska</surname><given-names>M</given-names></name><etal></etal></person-group><article-title>Bioactive composite for keratoprosthesis skirt</article-title>. <source>J Mech Behav Biomed Mater</source><year>2011</year>;<volume>4</volume>:<fpage>1700</fpage>–<lpage>8</lpage><pub-id pub-id-type="pmid">22098870</pub-id></mixed-citation></ref><ref id="b23"><label>23</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Bazan</surname><given-names>HE</given-names></name></person-group><article-title>Cellular and molecular events in corneal wound healing: significance of lipid signalling</article-title>. <source>Exp Eye Res</source><year>2005</year>;<volume>80</volume>:<fpage>453</fpage>–<lpage>63</lpage><pub-id pub-id-type="pmid">15781273</pub-id></mixed-citation></ref><ref id="b24"><label>24</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fukuda</surname><given-names>K</given-names></name><name><surname>Kumagai</surname><given-names>N</given-names></name><name><surname>Fujitsu</surname><given-names>Y</given-names></name><etal></etal></person-group><article-title>Fibroblasts as local immune modulators in ocular allergic disease</article-title>. <source>Allergol Int</source><year>2006</year>;<volume>55</volume>:<fpage>121</fpage>–<lpage>9</lpage><pub-id pub-id-type="pmid">17075248</pub-id></mixed-citation></ref><ref id="b25"><label>25</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cubitt</surname><given-names>CL</given-names></name><name><surname>Lausch</surname><given-names>RN</given-names></name><name><surname>Oakes</surname><given-names>JE</given-names></name></person-group><article-title>Differential regulation of granulocyte macrophage colony-stimulating factor gene expression in human corneal cells by pro-inflammatory cytokines</article-title>. <source>J Immunol</source><year>1994</year>;<volume>153</volume>:<fpage>232</fpage>–<lpage>40</lpage><pub-id pub-id-type="pmid">8207239</pub-id></mixed-citation></ref><ref id="b26"><label>26</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hong</surname><given-names>JW</given-names></name><name><surname>Liu</surname><given-names>JJ</given-names></name><name><surname>Lee</surname><given-names>JS</given-names></name><etal></etal></person-group><article-title>Proinflammatory chemokine induction in keratocytes and inflammatory cell infiltration into the cornea</article-title>. <source>Invest Ophthalmol Vis Sci</source><year>2001</year>;<volume>42</volume>:<fpage>2795</fpage>–<lpage>803</lpage><pub-id pub-id-type="pmid">11687520</pub-id></mixed-citation></ref><ref id="b27"><label>27</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Thakur</surname><given-names>A</given-names></name><name><surname>Willcox</surname><given-names>MD</given-names></name></person-group><article-title>Cytokine and lipid inflammatory mediator profile of human tears during contact lens associated inflammatory diseases</article-title>. <source>Exp Eye Res</source><year>1998</year>;<volume>67</volume>:<fpage>9</fpage>–<lpage>19</lpage><pub-id pub-id-type="pmid">9702174</pub-id></mixed-citation></ref><ref id="b28"><label>28</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Andersson</surname><given-names>SE</given-names></name><name><surname>Lexmuller</surname><given-names>K</given-names></name><name><surname>Johansson</surname><given-names>A</given-names></name><etal></etal></person-group><article-title>Tissue and intracellular pH in normal periarticular soft tissue and during different phases of antigen induced arthritis in the rat</article-title>. <source>J Rheumatol</source><year>1999</year>;<volume>26</volume>:<fpage>2018</fpage>–<lpage>24</lpage><pub-id pub-id-type="pmid">10493685</pub-id></mixed-citation></ref></ref-list></back></pmc><affiliations><list><country><li>Singapour</li></country><orgName><li>Université nationale de Singapour</li></orgName></list><tree><country name="Singapour"><noRegion><name sortKey="Tan, Xiao Wei" sort="Tan, Xiao Wei" uniqKey="Tan X" first="Xiao Wei" last="Tan">Xiao Wei Tan</name></noRegion><name sortKey="Beuerman, Roger W" sort="Beuerman, Roger W" uniqKey="Beuerman R" first="Roger W" last="Beuerman">Roger W. Beuerman</name><name sortKey="Beuerman, Roger W" sort="Beuerman, Roger W" uniqKey="Beuerman R" first="Roger W" last="Beuerman">Roger W. Beuerman</name><name sortKey="Beuerman, Roger W" sort="Beuerman, Roger W" uniqKey="Beuerman R" first="Roger W" last="Beuerman">Roger W. Beuerman</name><name sortKey="Khor, Khiam Aik" sort="Khor, Khiam Aik" uniqKey="Khor K" first="Khiam Aik" last="Khor">Khiam Aik Khor</name><name sortKey="Mehta, Jodhbir S" sort="Mehta, Jodhbir S" uniqKey="Mehta J" first="Jodhbir S" last="Mehta">Jodhbir S. Mehta</name><name sortKey="Mehta, Jodhbir S" sort="Mehta, Jodhbir S" uniqKey="Mehta J" first="Jodhbir S" last="Mehta">Jodhbir S. Mehta</name><name sortKey="Mehta, Jodhbir S" sort="Mehta, Jodhbir S" uniqKey="Mehta J" first="Jodhbir S" last="Mehta">Jodhbir S. Mehta</name><name sortKey="Mehta, Jodhbir S" sort="Mehta, Jodhbir S" uniqKey="Mehta J" first="Jodhbir S" last="Mehta">Jodhbir S. Mehta</name><name sortKey="Neoh, Koon Gee" sort="Neoh, Koon Gee" uniqKey="Neoh K" first="Koon Gee" last="Neoh">Koon Gee Neoh</name><name sortKey="Riau, Andri" sort="Riau, Andri" uniqKey="Riau A" first="Andri" last="Riau">Andri Riau</name><name sortKey="Shi, Zhi Long" sort="Shi, Zhi Long" uniqKey="Shi Z" first="Zhi Long" last="Shi">Zhi Long Shi</name><name sortKey="Tan, Anna C S" sort="Tan, Anna C S" uniqKey="Tan A" first="Anna C S" last="Tan">Anna C S. Tan</name><name sortKey="Tan, Donald" sort="Tan, Donald" uniqKey="Tan D" first="Donald" last="Tan">Donald Tan</name><name sortKey="Tan, Donald" sort="Tan, Donald" uniqKey="Tan D" first="Donald" last="Tan">Donald Tan</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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