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A modified collagen gel dressing promotes angiogenesis in a preclinical swine model of chronic ischemic wounds
Author(s) -
Elgharably Haytham,
Ganesh Kasturi,
Dickerson Jennifer,
Khanna Savita,
Abas Motaz,
Ghatak Piya Das,
Dixit Sriteja,
Bergdall Valerie,
Roy Sashwati,
Sen Chandan K.
Publication year - 2014
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/wrr.12229
Subject(s) - angiogenesis , wound healing , medicine , vascular endothelial growth factor , macrophage , fibroblast , basic fibroblast growth factor , ischemia , pathology , cytokine , type i collagen , growth factor , m2 macrophage , immunology , in vitro , biology , vegf receptors , biochemistry , receptor
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 bipedicle ischemic skin flaps on the backs of animals. Ischemia was verified by laser D oppler 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. In vitro, MCG up‐regulated expression of M rc‐1 (a reparative M 2 macrophage marker) and induced the expression of anti‐inflammatory cytokine interleukin ( IL )‐10 and of fibroblast growth factor‐basic (β‐ FGF ). An increased expression of CCR 2, an M 2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up‐regulation of transforming growth factor‐β, vascular endothelial growth factor, von W illebrand's factor, 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 that resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome, and postwound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds.