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Evaluation of an in situ chemically crosslinked hydrogel as a long-term vitreous substitute material
Currently there is no material that can be used as a long-term vitreous substitute, and this remains an unmet clinical need in ophthalmology. In this study, we developed an injectable, in situ chemically crosslinked hydrogel system and evaluated it in a rabbit model. The system consisted of two comp...
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Published in: | Acta biomaterialia 2013-02, Vol.9 (2), p.5022-5030 |
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creator | Tao, Yong Tong, Xinming Zhang, Yan Lai, Jingjing Huang, Yanbin Jiang, Yan-Rong Guo, Bao-Hua |
description | Currently there is no material that can be used as a long-term vitreous substitute, and this remains an unmet clinical need in ophthalmology. In this study, we developed an injectable, in situ chemically crosslinked hydrogel system and evaluated it in a rabbit model. The system consisted of two components, both based on multi-functional poly(ethylene glycol) (PEG) but with complementarily reactive end groups of thiol and active vinyl groups, respectively. The two components are mixed and injected as a solution mixture, react in vivo via the Michael addition route and form a chemically crosslinked hydrogel in situ. The linkages between the end groups and the backbone PEG chains are specially designed to ensure that the final network structure is hydrolysis-resistant. In the rabbit study and with an optimized operation protocol, we demonstrated that the hydrogel indeed formed in situ after injection, and remained transparent and stable during the study period of 9months without significant adverse reactions. In addition, the hydrogel formed in situ showed rheological properties very similar to the natural vitreous. Therefore, our study demonstrated that this in situ chemically crosslinked PEG gel system is suitable as a potential long-term vitreous substitute. |
doi_str_mv | 10.1016/j.actbio.2012.09.026 |
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In this study, we developed an injectable, in situ chemically crosslinked hydrogel system and evaluated it in a rabbit model. The system consisted of two components, both based on multi-functional poly(ethylene glycol) (PEG) but with complementarily reactive end groups of thiol and active vinyl groups, respectively. The two components are mixed and injected as a solution mixture, react in vivo via the Michael addition route and form a chemically crosslinked hydrogel in situ. The linkages between the end groups and the backbone PEG chains are specially designed to ensure that the final network structure is hydrolysis-resistant. In the rabbit study and with an optimized operation protocol, we demonstrated that the hydrogel indeed formed in situ after injection, and remained transparent and stable during the study period of 9months without significant adverse reactions. In addition, the hydrogel formed in situ showed rheological properties very similar to the natural vitreous. Therefore, our study demonstrated that this in situ chemically crosslinked PEG gel system is suitable as a potential long-term vitreous substitute.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2012.09.026</identifier><identifier>PMID: 23022890</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>adverse effects ; Animals ; Biocompatibility ; Cell Death - drug effects ; Cell Line ; Cross-Linking Reagents - pharmacology ; crosslinking ; Elastic Modulus - drug effects ; Electroretinography ; Endothelium, Corneal - drug effects ; Endothelium, Corneal - pathology ; ethylene glycol ; Fluorescein Angiography ; Fundus Oculi ; gels ; Humans ; hydrocolloids ; Hydrogel ; Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology ; Intraocular Pressure - drug effects ; Materials Testing ; ophthalmology ; Rabbit ; Rabbits ; Refractometry ; rheological properties ; Rheology - drug effects ; thiols ; Ultrasonography ; Vitreous Body - diagnostic imaging ; Vitreous Body - drug effects ; Vitreous Body - pathology ; Vitreous Body - surgery ; Vitreous substitute</subject><ispartof>Acta biomaterialia, 2013-02, Vol.9 (2), p.5022-5030</ispartof><rights>2012</rights><rights>Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-13373fc37ebbd092fdcaf479d3c2afc810ad911d2955d446e2b6655f0f9ee31e3</citedby><cites>FETCH-LOGICAL-c452t-13373fc37ebbd092fdcaf479d3c2afc810ad911d2955d446e2b6655f0f9ee31e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23022890$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tao, Yong</creatorcontrib><creatorcontrib>Tong, Xinming</creatorcontrib><creatorcontrib>Zhang, Yan</creatorcontrib><creatorcontrib>Lai, Jingjing</creatorcontrib><creatorcontrib>Huang, Yanbin</creatorcontrib><creatorcontrib>Jiang, Yan-Rong</creatorcontrib><creatorcontrib>Guo, Bao-Hua</creatorcontrib><title>Evaluation of an in situ chemically crosslinked hydrogel as a long-term vitreous substitute material</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>Currently there is no material that can be used as a long-term vitreous substitute, and this remains an unmet clinical need in ophthalmology. In this study, we developed an injectable, in situ chemically crosslinked hydrogel system and evaluated it in a rabbit model. The system consisted of two components, both based on multi-functional poly(ethylene glycol) (PEG) but with complementarily reactive end groups of thiol and active vinyl groups, respectively. The two components are mixed and injected as a solution mixture, react in vivo via the Michael addition route and form a chemically crosslinked hydrogel in situ. The linkages between the end groups and the backbone PEG chains are specially designed to ensure that the final network structure is hydrolysis-resistant. In the rabbit study and with an optimized operation protocol, we demonstrated that the hydrogel indeed formed in situ after injection, and remained transparent and stable during the study period of 9months without significant adverse reactions. In addition, the hydrogel formed in situ showed rheological properties very similar to the natural vitreous. Therefore, our study demonstrated that this in situ chemically crosslinked PEG gel system is suitable as a potential long-term vitreous substitute.</description><subject>adverse effects</subject><subject>Animals</subject><subject>Biocompatibility</subject><subject>Cell Death - drug effects</subject><subject>Cell Line</subject><subject>Cross-Linking Reagents - pharmacology</subject><subject>crosslinking</subject><subject>Elastic Modulus - drug effects</subject><subject>Electroretinography</subject><subject>Endothelium, Corneal - drug effects</subject><subject>Endothelium, Corneal - pathology</subject><subject>ethylene glycol</subject><subject>Fluorescein Angiography</subject><subject>Fundus Oculi</subject><subject>gels</subject><subject>Humans</subject><subject>hydrocolloids</subject><subject>Hydrogel</subject><subject>Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology</subject><subject>Intraocular Pressure - drug effects</subject><subject>Materials Testing</subject><subject>ophthalmology</subject><subject>Rabbit</subject><subject>Rabbits</subject><subject>Refractometry</subject><subject>rheological properties</subject><subject>Rheology - drug effects</subject><subject>thiols</subject><subject>Ultrasonography</subject><subject>Vitreous Body - diagnostic imaging</subject><subject>Vitreous Body - drug effects</subject><subject>Vitreous Body - pathology</subject><subject>Vitreous Body - surgery</subject><subject>Vitreous substitute</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNp9kE1v1DAQhi0EoqXwDxD4yCXBH3GcXJBQ1QJSJQ5tz5Zjj7denLjYzkr77_E2hSMnj-Rn3pl5EHpPSUsJ7T_vW23K5GPLCGUtGVvC-hfonA5yaKToh5e1lh1rJOnpGXqT854QPlA2vEZnjBPGhpGcI3t10GHVxccFR4f1gv2Csy8rNg8we6NDOGKTYs7BL7_A4oejTXEHAeuMNQ5x2TUF0owPviSIa8Z5nXKpAQXwrOuX1-EteuV0yPDu-b1A99dXd5ffm5uf335cfr1pTCdYaSjnkjvDJUyTJSNz1mjXydFyw7QzAyXajpRaNgphu64HNvW9EI64EYBT4Bfo05b7mOLvFXJRs88GQtDLaTVFmeRMUMZERbsNfbotgVOPyc86HRUl6uRX7dXmV538KjKq6re2fXiesE4z2H9Nf4VW4OMGOB2V3iWf1f1tTRCEUDLIvqvEl42AauLgIalsPCwGrE9girLR_3-HP1EXmMI</recordid><startdate>20130201</startdate><enddate>20130201</enddate><creator>Tao, Yong</creator><creator>Tong, Xinming</creator><creator>Zhang, Yan</creator><creator>Lai, Jingjing</creator><creator>Huang, Yanbin</creator><creator>Jiang, Yan-Rong</creator><creator>Guo, Bao-Hua</creator><general>Elsevier Ltd</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20130201</creationdate><title>Evaluation of an in situ chemically crosslinked hydrogel as a long-term vitreous substitute material</title><author>Tao, Yong ; Tong, Xinming ; Zhang, Yan ; Lai, Jingjing ; Huang, Yanbin ; Jiang, Yan-Rong ; Guo, Bao-Hua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-13373fc37ebbd092fdcaf479d3c2afc810ad911d2955d446e2b6655f0f9ee31e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>adverse effects</topic><topic>Animals</topic><topic>Biocompatibility</topic><topic>Cell Death - drug effects</topic><topic>Cell Line</topic><topic>Cross-Linking Reagents - pharmacology</topic><topic>crosslinking</topic><topic>Elastic Modulus - drug effects</topic><topic>Electroretinography</topic><topic>Endothelium, Corneal - drug effects</topic><topic>Endothelium, Corneal - pathology</topic><topic>ethylene glycol</topic><topic>Fluorescein Angiography</topic><topic>Fundus Oculi</topic><topic>gels</topic><topic>Humans</topic><topic>hydrocolloids</topic><topic>Hydrogel</topic><topic>Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology</topic><topic>Intraocular Pressure - drug effects</topic><topic>Materials Testing</topic><topic>ophthalmology</topic><topic>Rabbit</topic><topic>Rabbits</topic><topic>Refractometry</topic><topic>rheological properties</topic><topic>Rheology - drug effects</topic><topic>thiols</topic><topic>Ultrasonography</topic><topic>Vitreous Body - diagnostic imaging</topic><topic>Vitreous Body - drug effects</topic><topic>Vitreous Body - pathology</topic><topic>Vitreous Body - surgery</topic><topic>Vitreous substitute</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tao, Yong</creatorcontrib><creatorcontrib>Tong, Xinming</creatorcontrib><creatorcontrib>Zhang, Yan</creatorcontrib><creatorcontrib>Lai, Jingjing</creatorcontrib><creatorcontrib>Huang, Yanbin</creatorcontrib><creatorcontrib>Jiang, Yan-Rong</creatorcontrib><creatorcontrib>Guo, Bao-Hua</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Acta biomaterialia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tao, Yong</au><au>Tong, Xinming</au><au>Zhang, Yan</au><au>Lai, Jingjing</au><au>Huang, Yanbin</au><au>Jiang, Yan-Rong</au><au>Guo, Bao-Hua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of an in situ chemically crosslinked hydrogel as a long-term vitreous substitute material</atitle><jtitle>Acta biomaterialia</jtitle><addtitle>Acta Biomater</addtitle><date>2013-02-01</date><risdate>2013</risdate><volume>9</volume><issue>2</issue><spage>5022</spage><epage>5030</epage><pages>5022-5030</pages><issn>1742-7061</issn><eissn>1878-7568</eissn><abstract>Currently there is no material that can be used as a long-term vitreous substitute, and this remains an unmet clinical need in ophthalmology. In this study, we developed an injectable, in situ chemically crosslinked hydrogel system and evaluated it in a rabbit model. The system consisted of two components, both based on multi-functional poly(ethylene glycol) (PEG) but with complementarily reactive end groups of thiol and active vinyl groups, respectively. The two components are mixed and injected as a solution mixture, react in vivo via the Michael addition route and form a chemically crosslinked hydrogel in situ. The linkages between the end groups and the backbone PEG chains are specially designed to ensure that the final network structure is hydrolysis-resistant. In the rabbit study and with an optimized operation protocol, we demonstrated that the hydrogel indeed formed in situ after injection, and remained transparent and stable during the study period of 9months without significant adverse reactions. In addition, the hydrogel formed in situ showed rheological properties very similar to the natural vitreous. 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subjects | adverse effects Animals Biocompatibility Cell Death - drug effects Cell Line Cross-Linking Reagents - pharmacology crosslinking Elastic Modulus - drug effects Electroretinography Endothelium, Corneal - drug effects Endothelium, Corneal - pathology ethylene glycol Fluorescein Angiography Fundus Oculi gels Humans hydrocolloids Hydrogel Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology Intraocular Pressure - drug effects Materials Testing ophthalmology Rabbit Rabbits Refractometry rheological properties Rheology - drug effects thiols Ultrasonography Vitreous Body - diagnostic imaging Vitreous Body - drug effects Vitreous Body - pathology Vitreous Body - surgery Vitreous substitute |
title | Evaluation of an in situ chemically crosslinked hydrogel as a long-term vitreous substitute material |
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