Skin regenerated from cultured epithelial autografts on full-thickness burn wounds from 6 days to 5 years after grafting. A light, electron microscopic and immunohistochemical study

Abstract

Regeneration of skin from cultured keratinocyte autografts used in the treatment of full-thickness burn wounds was studied in 21 pediatric patients from 6 days to 5 years after grafting. Findings were compared both to controls of age- and site-matched normal skin and to controls for epithelial wound-healing, re-epithelialized interstices of meshed split-thickness skin grafts of comparable postgrafting age. Six days after transplantation, a mildly hypertrophic, flat epidermis with all normal strata had regenerated, and the process of de novo dermal-epidermal junction formation had begun. Hemidesmosomes, basal lamina, and anchoring fibrils reformed conjointly in punctate fashion along the attachment face of the grafts. Within 3 to 4 weeks, the dermal-epidermal junction was complete, but full maturation of anchoring fibrils required more than a year. The process was comparable to that observed in meshed graft interstices. Rete ridges regenerated from 6 weeks to 1 year after grafting. The subjacent connective tissue initially healed to form normal scar, but it remodeled dramatically, regenerated elastin, and resembled a true dermis within 4 to 5 years. Meshed-graft interstice controls showed no rete ridge regeneration, subepithelial connective tissue remodeling, or elastin production up to 5 years after grafting. Langerhans cells repopulated grafts within 1 week, and normal population densities were reached within 2 to 6 months. After 1 year, Langerhans cell densities were increased compared with normal skin but were lower than those in age-matched meshed graft controls. Melanocytes were present in cultures at the time of transplantation, but functional epidermal melanin units were not seen in groin- or axilla-derived grafts for 6 to 8 weeks or in sole-derived epidermis until a year or more after transplantation. Normal histologic features were maintained for years after grafting. Transitory pathologic changes including parakeratosis, dyskeratosis, and intraepithelial friction blister formation were infrequently observed. No dysplastic or premalignant changes were seen.