title: An in-situ forming skin substitute improves healing outcome in a hypertrophic scar model.
abstract: Wound repair requires a sequential series of biological events that begins with the deposition of a temporary scaffold within which cells can repair the skin. Without a scaffold, repair is essentially impossible. Aberrant wound healing, such as hypertrophic scarring or nonhealing, has a tremendous burden on healthcare and quality of life. Timely wound closure dramatically reduces the risk of infection and scarring. Cellular skin substitutes are opportune to meet this need. Our goal was to create an in-situ forming scaffold that can be easily combined with cells to rapidly form a dermal substitute within the wound bed. In this study, we evaluated the application of a polyvinyl alcohol-collagen-glycosaminoglycan-based biohybrid scaffold system in full-thickness wounds on a rabbit fibrotic ear model. Punch wounds (6 mm) were either untreated or filled with an acellular scaffold, a scaffold containing xenofibroblasts, or a scaffold containing xenofibroblasts expressing indoleamine 2,3-dioxygenase (IDO). Results demonstrated that (1) both acellular and IDO-expressing fibroblast in-situ forming scaffolds significantly reduced scar elevation index (1.24±0.05 and 1.25±0.03; p<0.05) and improved overall healing quality compared with xenofibroblast scaffolds and untreated wounds; (2) IDO-expressing fibroblast scaffolds significantly reduced T-cell infiltration into the scaffold-engrafted area (p<0.05); and (3) both IDO-expressing and acellular in-situ forming scaffolds demonstrated increased vessel-like and nerve-like structures (p<0.05). The results demonstrated that the use of the in-situ forming scaffold, and even more so when delivering IDO-expressing cells, improved healing outcome in full-thickness hypertrophic rabbit ear wounds.
authors.affiliation: Department of Surgery, University of British Columbia , Vancouver, Canada .
authors.forename: Ryan
authors.initials: R
authors.lastname: Hartwell
authors.forename: Malihe-Sadat
authors.initials: MS
authors.lastname: Poormasjedi-Meibod
authors.forename: Claudia
authors.initials: C
authors.lastname: Chavez-Munoz
authors.forename: Reza B
authors.initials: RB
authors.lastname: Jalili
authors.forename: Azadeh
authors.initials: A
authors.lastname: Hossenini-Tabatabaei
authors.forename: Aziz
authors.initials: A
authors.lastname: Ghahary
mesh_terms: D000328:Adult; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D017252:CD3 Complex / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D017439:Cicatrix, Hypertrophic; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D004423:Ear / Q000473:pathology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011817:Rabbits; D012867:Skin / Q000098:blood supply / Q000187:drug effects / Q000294:innervation; D017768:Skin, Artificial; D013601:T-Lymphocytes / Q000166:cytology; D054457:Tissue Scaffolds / Q000737:chemistry; D014945:Wound Healing / Q000187:drug effects
chemical_list: D001672:Biocompatible Materials; D017252:CD3 Complex; D024042:Collagen Type I; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020781:Matrix Metalloproteinase 1