Evaluation of a biodegradable matrix containing cultured human fibroblasts as a dermal replacement beneath meshed skin grafts on athymic mice

Abstract

Meshed, expanded split-thickness skin grafts (MSTSG) frequently achieve poor results when used to cover full-thickness wounds. Poor cosmetic and functional results occur in part because the epithelium that grows across the skin graft interstices lacks a dermis. We used a living dermal replacement composed of either polyglycolic acid (PGA) or polyglactin-910 (PGL) mesh containing confluent, cultured human fibroblasts. These grafts were applied to full-thickness wounds on athymic mice; widely expanded, 3:1 ratio human MSTSG was then placed over the dermal graft. Histologic examination of wounds during a 99-day period after graft placement showed that PGA/PGL-fibroblast grafts vascularized to the wound, and the MSTSG simultaneously vascularized to the PGA/PGL-fibroblast graft. Epithelialization from the MSTSG bridges proceeded rapidly across the surface of the PGA/PGL-fibroblast grafts, resulting in an epithelialized layer that covered a densely cellular substratum that resembled dermis. Basement membrane formation at the dermal-epidermal junction of the epithelialized interstices was confirmed by immunohistochemical microscopy. Minimal inflammatory reaction to the PGA/PGL-fibroblast grafts was seen. Grafts composed of PGA or PGL biodegradable meshes combined with cultured fibroblasts vascularize in full-thickness wounds, resulting in formation of organized tissue beneath the epithelialized surface that resembles dermis.