A Modified Collagen Gel Dressing Promotes Angiogenesis in a Pre-Clinical Swine Model of Chronic Ischemic Wounds
Identifieur interne : 003963 ( Pmc/Curation ); précédent : 003962; suivant : 003964A Modified Collagen Gel Dressing Promotes Angiogenesis in a Pre-Clinical Swine Model of Chronic Ischemic Wounds
Auteurs : Haytham Elgharably ; Kasturi Ganesh ; Jennifer Dickerson ; Savita Khanna ; Motaz Abas ; Piya Das Ghatak ; Sriteja Dixit ; Valerie Bergdall ; Sashwati Roy ; Chandan K. SenSource :
- Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society [ 1067-1927 ] ; 2014.
Abstract
We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full thickness excisional wounds were established in the center of bi- pedicle ischemic skin flaps on the backs of animals. Ischemia was verified by Laser Doppler imaging and MCG was applied to the test group of wounds. Seven days post- wounding, macrophage recruitment to the wound was significantly higher in MCG- treated ischemic wounds.
Url:
DOI: 10.1111/wrr.12229
PubMed: 25224310
PubMed Central: 4380279
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<front><div type="abstract" xml:lang="en"><p id="P1">We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full thickness excisional wounds were established in the center of bi- pedicle ischemic skin flaps on the backs of animals. Ischemia was verified by Laser Doppler imaging and MCG was applied to the test group of wounds. Seven days post- wounding, macrophage recruitment to the wound was significantly higher in MCG- treated ischemic wounds. <italic>In vitro</italic>
, MCG up-regulated expression of Mrc-1 (a reparative M2 macrophage marker) and induced the expression of anti-inflammatory cytokine IL-10 and of β-FGF. An increased expression of CCR2, a M2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up-regulation of TGF-β, VEGF, vWF, and collagen type I expression in MCG-treated ischemic wounds. At 21 days post-wounding, MCG-treated ischemic wounds displayed higher abundance of proliferating endothelial cells that formed mature vascular structures and increased blood flow to the wound. Fibroblast count was markedly higher in MCG-treated ischemic wound-edge tissue. In addition, MCG-treated wound-edge tissues displayed higher abundance of mature collagen with increased collagen type I:III deposition. Taken together, MCG helped mount a more robust inflammatory response which resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome and post-wound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds.</p>
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<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">9310939</journal-id>
<journal-id journal-id-type="pubmed-jr-id">21119</journal-id>
<journal-id journal-id-type="nlm-ta">Wound Repair Regen</journal-id>
<journal-id journal-id-type="iso-abbrev">Wound Repair Regen</journal-id>
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<issn pub-type="ppub">1067-1927</issn>
<issn pub-type="epub">1524-475X</issn>
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<article-meta><article-id pub-id-type="pmid">25224310</article-id>
<article-id pub-id-type="pmc">4380279</article-id>
<article-id pub-id-type="doi">10.1111/wrr.12229</article-id>
<article-id pub-id-type="manuscript">NIHMS628770</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
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<title-group><article-title>A Modified Collagen Gel Dressing Promotes Angiogenesis in a Pre-Clinical Swine Model of Chronic Ischemic Wounds</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Elgharably</surname>
<given-names>Haytham</given-names>
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<degrees>MD</degrees>
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<contrib contrib-type="author"><name><surname>Ganesh</surname>
<given-names>Kasturi</given-names>
</name>
<degrees>MD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Dickerson</surname>
<given-names>Jennifer</given-names>
</name>
<degrees>RVT</degrees>
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<contrib contrib-type="author"><name><surname>Khanna</surname>
<given-names>Savita</given-names>
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<degrees>PhD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Abas</surname>
<given-names>Motaz</given-names>
</name>
<degrees>BS</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Ghatak</surname>
<given-names>Piya Das</given-names>
</name>
<degrees>MS</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Dixit</surname>
<given-names>Sriteja</given-names>
</name>
<degrees>MS</degrees>
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<contrib contrib-type="author"><name><surname>Bergdall</surname>
<given-names>Valerie</given-names>
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<degrees>DVM</degrees>
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<contrib contrib-type="author"><name><surname>Roy</surname>
<given-names>Sashwati</given-names>
</name>
<degrees>PhD</degrees>
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<contrib contrib-type="author"><name><surname>Sen</surname>
<given-names>Chandan K.</given-names>
</name>
<degrees>PhD</degrees>
</contrib>
<aff id="A1">Departments of Surgery, Davis Heart & Lung Research Institute, Center for Regenerative Medicine and Cell based Therapies and Comprehensive Wound Center, The Ohio State University Wexner Medical Center, Columbus, Ohio 43210</aff>
</contrib-group>
<author-notes><corresp id="FN1"><bold>Address correspondence to:</bold>
Chandan K. Sen, PhD, 473 West 12th Avenue, 512 DHLRI, The Ohio State University Medical Center, Columbus, Ohio 43210, Tel. 614 247 7658; Fax 614 247 7818, <email>chandan.sen@osumc.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>16</day>
<month>3</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub"><day>08</day>
<month>1</month>
<year>2015</year>
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<pub-date pub-type="ppub"><season>Nov-Dec</season>
<year>2014</year>
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<pub-date pub-type="pmc-release"><day>08</day>
<month>1</month>
<year>2016</year>
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<volume>22</volume>
<issue>6</issue>
<fpage>720</fpage>
<lpage>729</lpage>
<pmc-comment>elocation-id from pubmed: 10.1111/wrr.12229</pmc-comment>
<abstract><p id="P1">We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full thickness excisional wounds were established in the center of bi- pedicle ischemic skin flaps on the backs of animals. Ischemia was verified by Laser Doppler imaging and MCG was applied to the test group of wounds. Seven days post- wounding, macrophage recruitment to the wound was significantly higher in MCG- treated ischemic wounds. <italic>In vitro</italic>
, MCG up-regulated expression of Mrc-1 (a reparative M2 macrophage marker) and induced the expression of anti-inflammatory cytokine IL-10 and of β-FGF. An increased expression of CCR2, a M2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up-regulation of TGF-β, VEGF, vWF, and collagen type I expression in MCG-treated ischemic wounds. At 21 days post-wounding, MCG-treated ischemic wounds displayed higher abundance of proliferating endothelial cells that formed mature vascular structures and increased blood flow to the wound. Fibroblast count was markedly higher in MCG-treated ischemic wound-edge tissue. In addition, MCG-treated wound-edge tissues displayed higher abundance of mature collagen with increased collagen type I:III deposition. Taken together, MCG helped mount a more robust inflammatory response which resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome and post-wound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds.</p>
</abstract>
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