644 Bioprinted skin integrates into full-thickness porcine wounds and supports healthy skin repair by modulating inflammation and tissue remodeling

Abstract

The purpose of this study is to assess the feasibility and efficacy of autologous bioprinted skin in the treatment of full-thickness porcine wounds. We hypothesize that bioprinted skin constructs will improve wound healing by modulating inflammation, skin remodeling, and epidermal maturation. Porcine keratinocytes, fibroblasts, pre-adipocytes, and endothelial cells were isolated, expanded, suspended in bioink, and bioprinted to form a biomimetic tri-layer skin construct. 5x5cm excisional full-thickness wounds were then treated with bioprinted skin from autologous or allogeneic cells, skin autograft or allograft, hydrogel, or left without treatment. Digital planimetry of photographs taken over 28 days demonstrated improved wound closure in autologous bioprinted skin treated wounds. Histological analysis confirmed these results and showed improved epidermal maturity, less fibrosis, and more normal collagen organization in the bioprinted autologous skin group. Hydrogel and skin allograft groups had increased total wound serum proteins and proteolytic activity, with an associated increase in inflammatory and proteolytic gene expression compared to the bioprinted autograft. These findings suggest that treatment of full-thickness porcine wounds with hydrogel generates inflammatory wound healing and protease activity. Alternatively, bioprinted constructs composed of autologous skin cells embedded in hydrogel induce healthy, pro-remodeling protease activity, resulting in normal wound healing. Taken together, our results suggest that bioprinted autologous skin rapidly integrates into the wound to support skin regeneration and confirms the feasibility of skin bioprinting technology for clinical treatment of full-thickness wounds in human patients.