Use of a fibrin-based system for enhancing angiogenesis and modulating inflammation in the treatment of hyperglycemic wounds
Abstract The complex pathophysiology of chronic ulceration in diabetic patients is poorly understood; diabetes-related lower limb amputation is a major health issue, which has limited effective treatment regimes in the clinic. This study attempted to understand the complex pathology of hyperglycemic...
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| Veröffentlicht in: | Biomaterials 2014-02, Vol.35 (6), p.2001-2010 |
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| container_end_page | 2010 |
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| container_issue | 6 |
| container_start_page | 2001 |
| container_title | Biomaterials |
| container_volume | 35 |
| creator | Kulkarni, M O'Loughlin, A Vazquez, R Mashayekhi, K Rooney, P Greiser, U O'Toole, E O'Brien, T Malagon, Maria M Pandit, A |
| description | Abstract The complex pathophysiology of chronic ulceration in diabetic patients is poorly understood; diabetes-related lower limb amputation is a major health issue, which has limited effective treatment regimes in the clinic. This study attempted to understand the complex pathology of hyperglycemic wound healing by showing profound changes in gene expression profiles in wounded human keratinocytes in hyperglycemic conditions compared to normal glucose conditions. In the hyper-secretory wound microenvironment of hyperglycemia, Rab18, a secretory control molecule, was found to be significantly downregulated. Using a biomaterial platform for dual therapy targeting the two distinct pathways, this study aimed to resolve the major dysregulated pathways in hyperglycemic wound healing. To complement Rab18, and promote angiogenesis eNOS was also targeted, and this novel Rab18-eNOS therapy via a dynamically controlled ‘fibrin-in-fibrin’ delivery system, demonstrated enhanced wound closure, by increasing functional angiogenesis and reducing inflammation, in an alloxan-induced hyperglycemic preclinical ear ulcer model of compromised wound healing. |
| doi_str_mv | 10.1016/j.biomaterials.2013.11.003 |
| format | Article |
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This study attempted to understand the complex pathology of hyperglycemic wound healing by showing profound changes in gene expression profiles in wounded human keratinocytes in hyperglycemic conditions compared to normal glucose conditions. In the hyper-secretory wound microenvironment of hyperglycemia, Rab18, a secretory control molecule, was found to be significantly downregulated. Using a biomaterial platform for dual therapy targeting the two distinct pathways, this study aimed to resolve the major dysregulated pathways in hyperglycemic wound healing. To complement Rab18, and promote angiogenesis eNOS was also targeted, and this novel Rab18-eNOS therapy via a dynamically controlled ‘fibrin-in-fibrin’ delivery system, demonstrated enhanced wound closure, by increasing functional angiogenesis and reducing inflammation, in an alloxan-induced hyperglycemic preclinical ear ulcer model of compromised wound healing.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2013.11.003</identifier><identifier>PMID: 24331702</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Advanced Basic Science ; Angiogenesis ; Animals ; Cell Proliferation - drug effects ; Dentistry ; Diabetes ; Fibrin - chemistry ; Gene therapy ; Humans ; Hyperglycemia - drug therapy ; Hyperglycemia - metabolism ; Immunohistochemistry ; Inflammation ; Inflammation - metabolism ; Keratinocyte ; Keratinocytes - cytology ; Keratinocytes - metabolism ; Neovascularization, Physiologic - drug effects ; Nitric Oxide Synthase Type III - metabolism ; rab GTP-Binding Proteins - metabolism ; Rabbits ; Wound healing ; Wound Healing - physiology</subject><ispartof>Biomaterials, 2014-02, Vol.35 (6), p.2001-2010</ispartof><rights>Elsevier Ltd</rights><rights>2013 Elsevier Ltd</rights><rights>Copyright © 2013 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-d992f4bb1150d4e35b90a084884d3140fa3de2e8a1680b9bb68b9e96b9fe9413</citedby><cites>FETCH-LOGICAL-c435t-d992f4bb1150d4e35b90a084884d3140fa3de2e8a1680b9bb68b9e96b9fe9413</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biomaterials.2013.11.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24331702$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kulkarni, M</creatorcontrib><creatorcontrib>O'Loughlin, A</creatorcontrib><creatorcontrib>Vazquez, R</creatorcontrib><creatorcontrib>Mashayekhi, K</creatorcontrib><creatorcontrib>Rooney, P</creatorcontrib><creatorcontrib>Greiser, U</creatorcontrib><creatorcontrib>O'Toole, E</creatorcontrib><creatorcontrib>O'Brien, T</creatorcontrib><creatorcontrib>Malagon, Maria M</creatorcontrib><creatorcontrib>Pandit, A</creatorcontrib><title>Use of a fibrin-based system for enhancing angiogenesis and modulating inflammation in the treatment of hyperglycemic wounds</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Abstract The complex pathophysiology of chronic ulceration in diabetic patients is poorly understood; diabetes-related lower limb amputation is a major health issue, which has limited effective treatment regimes in the clinic. This study attempted to understand the complex pathology of hyperglycemic wound healing by showing profound changes in gene expression profiles in wounded human keratinocytes in hyperglycemic conditions compared to normal glucose conditions. In the hyper-secretory wound microenvironment of hyperglycemia, Rab18, a secretory control molecule, was found to be significantly downregulated. Using a biomaterial platform for dual therapy targeting the two distinct pathways, this study aimed to resolve the major dysregulated pathways in hyperglycemic wound healing. To complement Rab18, and promote angiogenesis eNOS was also targeted, and this novel Rab18-eNOS therapy via a dynamically controlled ‘fibrin-in-fibrin’ delivery system, demonstrated enhanced wound closure, by increasing functional angiogenesis and reducing inflammation, in an alloxan-induced hyperglycemic preclinical ear ulcer model of compromised wound healing.</description><subject>Advanced Basic Science</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Cell Proliferation - drug effects</subject><subject>Dentistry</subject><subject>Diabetes</subject><subject>Fibrin - chemistry</subject><subject>Gene therapy</subject><subject>Humans</subject><subject>Hyperglycemia - drug therapy</subject><subject>Hyperglycemia - metabolism</subject><subject>Immunohistochemistry</subject><subject>Inflammation</subject><subject>Inflammation - metabolism</subject><subject>Keratinocyte</subject><subject>Keratinocytes - cytology</subject><subject>Keratinocytes - metabolism</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Nitric Oxide Synthase Type III - metabolism</subject><subject>rab GTP-Binding Proteins - metabolism</subject><subject>Rabbits</subject><subject>Wound healing</subject><subject>Wound Healing - physiology</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUk2L1TAULaI4z9G_IMGVm9bcJu00LgQZP2HAheM65OP2vTzb5JmkSsEfb8obRVy5Coece849h1tVz4A2QKF_cWy0C7PKGJ2aUtNSYA1AQym7V-1guBrqTtDufrWjwNta9NBeVI9SOtKCKW8fVhctZwyuaLurfn5JSMJIFBmdjs7XWiW0JK0p40zGEAn6g_LG-T1Rfu_CHj0mlwqwZA52mVTe_pwfJzWXpVzwBZB8QJIjqjyjz5vBYT1h3E-rwdkZ8iMs3qbH1YOxJMAnd-9ldfvu7e31h_rm0_uP169vasNZl2srRDtyrQE6ajmyTguq6MCHgVtWIo2KWWxxUNAPVAut-0ELFL0WIwoO7LJ6fpY9xfBtwZTl7JLBaVIew5Ik8F60QAc6FOrLM9XEkFLEUZ6im1VcJVC5lS-P8u_y5Va-BJCl_DL89M5n0TPaP6O_2y6EN2cClrDfHUaZjENv0LqIJksb3P_5vPpHxkzOO6Omr7hiOoYl-m0GZGollZ-3M9iuAFgR4UDZL3qMs84</recordid><startdate>20140201</startdate><enddate>20140201</enddate><creator>Kulkarni, M</creator><creator>O'Loughlin, A</creator><creator>Vazquez, R</creator><creator>Mashayekhi, K</creator><creator>Rooney, P</creator><creator>Greiser, U</creator><creator>O'Toole, E</creator><creator>O'Brien, T</creator><creator>Malagon, Maria M</creator><creator>Pandit, A</creator><general>Elsevier Ltd</general><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>20140201</creationdate><title>Use of a fibrin-based system for enhancing angiogenesis and modulating inflammation in the treatment of hyperglycemic wounds</title><author>Kulkarni, M ; O'Loughlin, A ; Vazquez, R ; Mashayekhi, K ; Rooney, P ; Greiser, U ; O'Toole, E ; O'Brien, T ; Malagon, Maria M ; Pandit, A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-d992f4bb1150d4e35b90a084884d3140fa3de2e8a1680b9bb68b9e96b9fe9413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Advanced Basic Science</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Cell Proliferation - drug effects</topic><topic>Dentistry</topic><topic>Diabetes</topic><topic>Fibrin - chemistry</topic><topic>Gene therapy</topic><topic>Humans</topic><topic>Hyperglycemia - drug therapy</topic><topic>Hyperglycemia - metabolism</topic><topic>Immunohistochemistry</topic><topic>Inflammation</topic><topic>Inflammation - metabolism</topic><topic>Keratinocyte</topic><topic>Keratinocytes - cytology</topic><topic>Keratinocytes - metabolism</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Nitric Oxide Synthase Type III - metabolism</topic><topic>rab GTP-Binding Proteins - metabolism</topic><topic>Rabbits</topic><topic>Wound healing</topic><topic>Wound Healing - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kulkarni, M</creatorcontrib><creatorcontrib>O'Loughlin, A</creatorcontrib><creatorcontrib>Vazquez, R</creatorcontrib><creatorcontrib>Mashayekhi, K</creatorcontrib><creatorcontrib>Rooney, P</creatorcontrib><creatorcontrib>Greiser, U</creatorcontrib><creatorcontrib>O'Toole, E</creatorcontrib><creatorcontrib>O'Brien, T</creatorcontrib><creatorcontrib>Malagon, Maria M</creatorcontrib><creatorcontrib>Pandit, A</creatorcontrib><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>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kulkarni, M</au><au>O'Loughlin, A</au><au>Vazquez, R</au><au>Mashayekhi, K</au><au>Rooney, P</au><au>Greiser, U</au><au>O'Toole, E</au><au>O'Brien, T</au><au>Malagon, Maria M</au><au>Pandit, A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Use of a fibrin-based system for enhancing angiogenesis and modulating inflammation in the treatment of hyperglycemic wounds</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2014-02-01</date><risdate>2014</risdate><volume>35</volume><issue>6</issue><spage>2001</spage><epage>2010</epage><pages>2001-2010</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Abstract The complex pathophysiology of chronic ulceration in diabetic patients is poorly understood; diabetes-related lower limb amputation is a major health issue, which has limited effective treatment regimes in the clinic. This study attempted to understand the complex pathology of hyperglycemic wound healing by showing profound changes in gene expression profiles in wounded human keratinocytes in hyperglycemic conditions compared to normal glucose conditions. In the hyper-secretory wound microenvironment of hyperglycemia, Rab18, a secretory control molecule, was found to be significantly downregulated. Using a biomaterial platform for dual therapy targeting the two distinct pathways, this study aimed to resolve the major dysregulated pathways in hyperglycemic wound healing. 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| identifier | ISSN: 0142-9612 |
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| subjects | Advanced Basic Science Angiogenesis Animals Cell Proliferation - drug effects Dentistry Diabetes Fibrin - chemistry Gene therapy Humans Hyperglycemia - drug therapy Hyperglycemia - metabolism Immunohistochemistry Inflammation Inflammation - metabolism Keratinocyte Keratinocytes - cytology Keratinocytes - metabolism Neovascularization, Physiologic - drug effects Nitric Oxide Synthase Type III - metabolism rab GTP-Binding Proteins - metabolism Rabbits Wound healing Wound Healing - physiology |
| title | Use of a fibrin-based system for enhancing angiogenesis and modulating inflammation in the treatment of hyperglycemic wounds |
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