Cultured skin substitutes reduce donor skin harvesting for closure of excised, full-thickness burns

Abstract

Objective: Comparison of cultured skin substitutes (CSS) and split-thickness skin autograft (AG) was performed to assess whether donor-site harvesting can be reduced quantitatively and whether functional and cosmetic outcome is similar qualitatively in the treatment of patients with massive cutaneous burns.

Summary background data: Cultured skin substitutes consisting of collagen-glycosaminoglycan substrates populated with autologous fibroblasts and keratinocytes have been shown to close full-thickness skin wounds in preclinical and clinical studies with acceptable functional and cosmetic results.

Methods: Qualitative outcome was compared between CSS and AG in 45 patients on an ordinal scale (0, worst; 10, best) with primary analyses at postoperative day 28 and after about 1 year for erythema, pigmentation, pliability, raised scar, epithelial blistering, and surface texture. In the latest 12 of the 45 patients, tracings were performed of donor skin biopsies and wounds treated with CSS at postoperative days 14 and 28 to calculate percentage engraftment, the ratio of closed wound:donor skin areas, and the percentage of total body surface area closed with CSS.

Results: Measures of qualitative outcome of CSS or AG were not different statistically at 1 year after grafting. Engraftment at postoperative day 14 exceeded 75% in the 12 patients evaluated. The ratio of closed wound:donor skin areas for CSS at postoperative day 28 was significantly greater than for conventional 4:1 meshed autografts. The percentage of total body surface area closed with CSS at postoperative day 28 was significantly less than with AG.

Conclusions: The requirement for harvesting of donor skin for CSS was less than for conventional skin autografts. These results suggest that acute-phase recovery of patients with extensive burns is facilitated and that complications are reduced by the use of CSS together with conventional skin grafting.

Figure 1. Composition of autologous cultured skin substitutes (CSS) in vitro. CSS were (A) approximately 40 cm² in area and (B) approximately 0.3 mm thick. They consisted of a well-stratified and cornified epithelium attached biologically to a reticulated sponge of bovine skin collagen and chondroitin-sulfate populated with dermal fibroblasts. Scale = 0.256 mm between inset notches.

Figure 2. Clinical photos after grafting of cultured skin substitutes (CSS) and meshed, split-thickness skin autograft (AG) on a patient with 90% total body surface area burns. Anterior torso (A, C) includes comparative sites. Posterior torso (B, D) was treated entirely with CSS. (A, B) Postoperative days 73 and 59 respectively; (C, D) postoperative days 337 and 323, respectively. Grafted areas are within dashed lines. Scale in centimeters.

Figure 3. Percentage engraftment of cultured skin substitutes (CSS) and meshed, split-thickness skin autograft (AG) at postoperative days 14 and 28 (n = 12). No statistical differences were found between CSS and AG by repeated measures analysis of variance.

Figure 4. Donor-site utilization at postoperative day 28 (n = 12). Ratios of closed wound:donor skin areas for cultured skin substitutes (66.8 ± 16.3) and autograft (4.0 ± 0.0) were significant at the P < .01 level of confidence by one-sample t test.

Figure 5. Correlation of the percentage total body surface area (%TBSA) full-thickness burn (n = 12) with (A) the percentage of site closed with cultured skin substitutes (CSS) at postoperative day 14 showed no statistical correlation and (B) %TBSA closed with CSS at postoperative day 28 showed a positive correlation that was statistically significant (P < .01).

Figure 6. Site assessments at postoperative days 7 and 14 (n = 45). (A) Color, (B) keratinization, (C) percentage site covered, (D) percentage of sites with exudate. Significant differences (*P < .05) between graft types at marked intervals are indicated.

Figure 7. Qualitative outcome versus months after surgery (n = 45). (A) Erythema, (B) pigmentation, (C) pliability, (D) raised scar, (E) epidermal blisters, (F) surface texture. Significant differences (*P < .05) between graft types at marked intervals are indicated.

Figure 8. Histology of healed cultured skin substitutes (CSS) and meshed, split-thickness skin autograft (AG). (A) CSS at >1 year; (B) AG at >1 year. Scale bars = 0.256 mm between inset notches.