title: A modified collagen gel dressing promotes angiogenesis in a preclinical swine model of chronic ischemic wounds.
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 bipedicle 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. In vitro, MCG up-regulated expression of Mrc-1 (a reparative M2 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 CCR2, an 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 transforming growth factor-β, vascular endothelial growth factor, von Willebrand'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.
authors.affiliation: Department of Surgery, Davis Heart & Lung Research Institute, Center for Regenerative Medicine and Cell Based Therapies, Comprehensive Wound Center, The Ohio State University Wexner Medical Center, Columbus, Ohio.
authors.forename: Haytham
authors.initials: H
authors.lastname: Elgharably
authors.forename: Kasturi
authors.initials: K
authors.lastname: Ganesh
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dickerson
authors.forename: Savita
authors.initials: S
authors.lastname: Khanna
authors.forename: Motaz
authors.initials: M
authors.lastname: Abas
authors.forename: Piya Das
authors.initials: PD
authors.lastname: Ghatak
authors.forename: Sriteja
authors.initials: S
authors.lastname: Dixit
authors.forename: Valerie
authors.initials: V
authors.lastname: Bergdall
authors.forename: Sashwati
authors.initials: S
authors.lastname: Roy
authors.forename: Chandan K
authors.initials: CK
authors.lastname: Sen
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D001458:Bandages; D002908:Chronic Disease; D003094:Collagen / Q000494:pharmacology*; D004195:Disease Models, Animal; D005782:Gels; D007150:Immunohistochemistry; D007511:Ischemia / Q000150:complications; D013524:Surgical Flaps; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing; D014947:Wounds and Injuries / Q000209:etiology / Q000473:pathology / Q000628:therapy*
chemical_list: D043925:Angiogenesis Inducing Agents; D005782:Gels; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen