title: A modified collagen gel enhances healing outcome in a preclinical swine model of excisional wounds.
abstract: Collagen-based dressings are of great interest in wound care. However, evidence supporting their mechanism of action is scanty. This work provides first results from a preclinical swine model of excisional wounds, elucidating the mechanism of action of a modified collagen gel (MCG) dressing. Following wounding, wound-edge tissue was collected at specific time intervals (3, 7, 14, and 21 days postwounding). On day 7, histological analysis showed significant increase in the length of rete ridges, suggesting improved biomechanical properties of the healing wound tissue. Rapid and transient mounting of inflammation is necessary for efficient healing. MCG significantly accelerated neutrophil and macrophage recruitment to the wound site on day 3 and day 7 with successful resolution of inflammation on day 21. MCG induced monocyte chemotactic protein-1 expression in neutrophil-like human promyelocytic leukemia-60 cells in vitro. In vivo, MCG-treated wound tissue displayed elevated vascular endothelial growth factor expression. Consistently, MCG-treated wounds displayed significantly higher abundance of endothelial cells with increased blood flow to the wound area indicating improved vascularization. This observation was explained by the finding that MCG enhanced proliferation of wound-site endothelial cells. In MCG-treated wound tissue, Masson's trichrome and picrosirius red staining showed higher abundance of collagen and increased collagen type I:III ratio. This work presents first evidence from a preclinical setting explaining how a collagen-based dressing may improve wound closure by targeting multiple key mechanisms. The current findings warrant additional studies to determine whether the responses to the MCG are different from other collagen-based products used in clinical setting.
authors.affiliation: Department of Surgery, Davis Heart & Lung Research Institute, Center for Regenerative Medicine and Cell-B Therapies and Comprehensive Wound Center, The Ohio State University Wexner Medical Center, Columbus, Ohio 43210, USA.
authors.forename: Haytham
authors.initials: H
authors.lastname: Elgharably
authors.forename: Sashwati
authors.initials: S
authors.lastname: Roy
authors.forename: Savita
authors.initials: S
authors.lastname: Khanna
authors.forename: Motaz
authors.initials: M
authors.lastname: Abas
authors.forename: Piya
authors.initials: P
authors.lastname: Dasghatak
authors.forename: Amitava
authors.initials: A
authors.lastname: Das
authors.forename: Kareem
authors.initials: K
authors.lastname: Mohammed
authors.forename: Chandan K
authors.initials: CK
authors.lastname: Sen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D003094:Collagen / Q000494:pharmacology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005782:Gels; D005786:Gene Expression Regulation / Q000187:drug effects; D018919:Neovascularization, Physiologic; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000098:blood supply / Q000293:injuries* / Q000378:metabolism; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D014945:Wound Healing / Q000502:physiology*; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D018932:Chemokine CCL2; D005782:Gels; D042461:Vascular Endothelial Growth Factor A; D012313:RNA; D003094:Collagen