Topical sulfamylon reduces engraftment of cultured skin substitutes on athymic mice

Sulfamylon (mafenide acetate) remains extremely valuable for the control of the bacterial contamination of burn wounds, but it is cytotoxic to cultured keratinocytes used for wound closure. Because composite skin substitutes develop a partial epidermal barrier in vitro, they may hypothetically tolerate the use of topical Sulfamylon. To test this hypothesis, cultured skin substitutes were prepared from cultured human fibroblasts; keratinocytes were attached to these collagen-based substrates, which were grafted to full-thickness wounds in athymic mice (n = 8 per group). Wounds were irrigated twice daily with 5% (wt/vol) Sulfamylon solution or with a formulation of noncytotoxic antimicrobials (0% Sulfamylon). On day 9 after grafting, the wounds were treated with dry dressings and assessed at 4 weeks for expression of human leukocyte antigens-A, B, C and at 2, 3, and 4 weeks for percentage of original wound area and surface electrical capacitance in picofarads (pF). Data were analyzed for statistical significance (P < .05) by Fisher's exact test, Student's t test, and repeated measures analysis of variance: [table: see text] The data demonstrate that irrigation of cultured skin substitutes with a solution of 5% Sulfamylon results in smaller wound area, fewer wounds that contain human cells, and greater surface hydration (higher surface electrical capacitance) than irrigation with noncytotoxic antimicrobial agents. These results support the conclusion that cultured skin substitutes of this type do not tolerate the chemical toxicity of Sulfamylon as well as skin autografts. Further improvements in the properties of the epidermal barrier of cultured skin substitutes may facilitate the use of Sulfamylon or other potent antimicrobial agents for the management of microbial contamination during engraftment of transplanted skin cells.