TOPICAL NUTRIENTS PROMOTE ENGRAFTMENT AND INHIBIT WOUND CONTRACTION OF CULTURED SKIN SUBSTITUTES IN ATHYMIC MICE

Routine treatment of burns with cultured skin substitutes (CSS) has be en limited by poor engraftment and by scarring, Hypothetically, topica l application of essential nutrients and/or growth factors may support epithelial survival temporarily during graft vascularization, CSS, co mposed of human epidermal keratinocytes and dermal fibroblasts attache d to collagen-glycosaminoglycan substrates, were incubated for 19 d in media optimized for keratinocytes. CSS, human xenografts, murine auto grafts, or no grafts were applied orthotopically to full-thickness ski n wounds (2 x 2 cm) in athymic mice, Wounds were irrigated for 14 d wi th 1 ml/d modified cell culture medium or with saline containing epide rmal growth factor, or were treated with dry dressings, After 6 weeks, treated sites were scored for percentage original wound area (mean +/ - SEM) and percentage HLA-ABC-positive healed wounds [(number positive /n) x 100], and tested for significance (analysis of variance, p < 0.0 001; Tukey test, p < 0.05), The data showed that CSS irrigated with nu trient medium were not statistically different in wound area (67.8 +/- 5.1%) from murine autografts (63.3 +/- 2.9%) but were statistically l arger than human xenograft, no graft, or CSS treated with saline irrig ation or dry dressings, HLA-ABC expression was 100% in CSS with nutrie nt irrigation, 86% in CSS with saline irrigation, 83% in CSS without i rrigation, and 75% in xenografts with nutrient irrigation, These findi ngs suggest that availability of essential nutrients supports keratino cyte viability during graft vascularization of CSS.