An in-situ forming skin substitute improves healing outcome in a hypertrophic scar model

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.