Bio-Inspired Skin Reconstruction Using Intraoperative Autologous Epidermal Stem Cell-Enhanced Composite Grafts: A Randomized Trial.

Full-thickness wounds remain a major clinical challenge, and tissue-engineered skin using epidermal stem cells (EpiSCs) offers a promising strategy for bio-inspired reconstruction. In this randomized controlled trial, 232 patients with full-thickness defects (≥ 9 cm2) received either standard treatment (acellular dermal matrix [ADM] + split-thickness skin graft [STSG], n = 112) or cell therapy (ADM + STSG + EpiSC suspension, n = 120). Autologous EpiSCs were prepared intraoperatively in a single step, avoiding prolonged in vitro expansion. The primary outcome was 6-month scar quality assessed by the Vancouver Scar Scale (VSS), while secondary outcomes included 2-week healing and 3-month recurrence. Compared with standard treatment, cell therapy produced significantly lower total VSS scores (median 3.0 vs. 6.0, p < 0.001) and improved complete wound healing at 2 weeks (80/120 [66.7%] vs. 61/112 [54.5%]; adjusted odds ratios [OR] = 1.87, 95% confidence interval [CI] 1.06-3.28, p = 0.029). Complete healing at 2 weeks was associated with reduced 3-month recurrence (adjusted OR = 0.26, 95% CI 0.09-0.75, p = 0.012). These findings support intraoperative EpiSC-enhanced composite grafting as an effective and clinically translatable approach for rapid closure and improved long-term scar outcomes.